BREAST CANCER

Mammograms After 65 Can Save Lives-(HealthDayNews-17/11/2003)

Is it cost-effective to continue to use mammograms to screen women for breast cancer after age 65? The answer appears to be a qualified yes, a new study reports. An analysis in the Nov. 18 issue of the Annals of Internal Medicine finds, in general, the benefits of screening women over 65 for breast cancer every two years outweigh the costs and possible side effects, like false-positive results. That conclusion is drawn from a review of 10 previously published cost-effectiveness studies, the researchers say. Based on current medical spending, it costs an additional "$34,000 to $88,000 per year-of-life saved" to perform those biennial tests, the study found. "It's very comparable with other spending," says Dr. Jeanne Mandelblatt, a cancer outcomes researcher at Georgetown University's Lombardi Cancer Center and the lead author of the study. Treating adults who have mild to moderate hypertension with a blood pressure-lowering medication, for example, costs roughly the same: $16,000 to $72,000 per year-of-life saved, the researchers note.

Many older women are being screened annually, "especially because Medicare covers that," says Cheryl Kidd, director of education at the Susan G. Komen Breast Cancer Foundation in Dallas. The cost-benefit question looms, in part, because of a lack of data on the issue. Few older women were included in the original trials of mammography screening, according to the report. Women are urged to have an annual mammogram beginning at age 40 to detect breast cancer before symptoms arise. Experts agree the years of life saved more than justify the cost of performing the tests. But some women over 65 who suffer from other health problems, like diabetes, heart disease, hypertension or other cancers, may not realize the full benefit of early breast cancer detection. A woman might die of a heart attack, for instance, before breast cancer would kill her, Mandelblatt says. The study authors also note that diagnosing breast cancer and treating it in someone dying of another disease can reduce her quality of life, especially if early detection and treatment fail to extend her life. Individual health status also makes a difference.

A vigorous 80-year-old may receive more benefit from mammography screening than a frail 70-year-old, Mandelblatt says. Screening "becomes more costly and harms begin to outweigh benefits in the sickest women, such as those with dementia" or other conditions that limit life expectancy, the authors note. The report's findings are consistent with guidelines established by the American Cancer Society. The society recommends women have a mammography every year beginning at age 40, citing no upper limit on age. It does say further research is needed on the risks and benefits for women with serious chronic health problems or short life expectancy. For these women, especially, screening is "a personal choice," says Dr. Cheryl Perkins, the Komen Foundation's senior clinical advisor. "If she feels that screening would increase her quality of life and she feels it would increase her quality of health, then I think it's beneficial."

Mandelblatt says the new report is intended to guide future research and policymaking, not a woman's decision to get screened or not. Women still need to make those decisions in consultation with their health-care providers, she says. While many Americans remain squeamish about rationing health care, studies like this one help to put a fine point on the costs, benefits and risks of investing in certain services and tests, the researchers say. "If you have unlimited funds, it's not an issue," Mandelblatt says. "If you're in a third-world country, $100 per year-of-life saved may be more than you can afford."

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Partial-Breast Irradiation an Unproven Therapy-(HealthDayNews-16/11/2003)

It's called partial-breast irradiation, and proponents see it as a promising alternative treatment for breast cancer patients who've just had a lumpectomy Thousands of women have already sought out the therapy, which requires just one week or less of radiation after breast cancer is diagnosed, instead of the six or seven weeks required for whole-breast irradiation. But its long-term benefits remain unproven, some experts caution. That's why the National Cancer Institute has launched a major study of this experimental therapy this fall, to offer women sound guidance based on years of observation. Dr. Gary Freedman is a radiation oncologist at Fox Chase Cancer Center in Philadelphia who is urging a cautious approach. He says some studies looking at the benefits of partial-breast irradiation five years after treatment have produced acceptable results. But, he adds, "five-year results aren't long enough to say, 'This is a standard alternative.'"

nterest in partial-breast irradiation heightened after the U.S. Food and Drug Administration approved a new radiation device in 2002. Bearing radioactive seeds, it's implanted after a lumpectomy into the site from which the tumor has been removed and then delivers radiation to that area only, not the entire breast. The therapy is proving popular with women who find the short timetable far more convenient. Partial-breast irradiation is based on the idea that most recurrences of cancer appear at the site of the original tumor, not other parts of the same breast. Whole-breast irradiation works by treating the entire breast with radiation, to prevent undetected cancer cells that might have escaped from the original tumor from spreading to other parts of the same breast.

Freedman presented a study last month at the annual meeting of the American Society of Therapeutic Radiology and Oncology that compared whole-breast to partial-breast irradiation. He reported that the follow-up data on whole-breast irradiation is much longer than that for the newer technique. His research also showed that 15 years after a lumpectomy, the cancer recurrence rates were nearly the same at both the original tumor site as well as other parts of the breast. Freedman evaluated 2,700 women who had whole-breast irradiation, to assess the cancer recurrence rate in that breast. After five years, the recurrence rate at the original tumor site was 3 percent, while it was 1 percent in other parts of the same breast. After 10 years, it was 6 percent at the original site and 2 percent in other parts of the same breast. But after 15 years, the recurrence rates were 9 percent at the initial cancer site and 7 percent in other parts of the same breast. This suggests that whole-breast irradiation must remain the standard -- at least for now, he says. "The burden of proof is on the people who want to treat less than the whole breast," says Freedman. Nationwide, Freedman says, "a handful of experts have been believers and major proponents" of partial-breast irradiation.

But even though the device has been approved by the FDA, partial-breast irradiation is still considered experimental, the American Cancer Society says. The FDA approved the device based on data from 25 women at eight medical centers who had it implanted after a lumpectomy, the cancer society says. The device uses a kind of radiation called brachytherapy, in which radioactive seeds or pellets are placed in the area being treated. It is implanted into the breast at the lumpectomy site. Then the device's balloon is inflated and the radioactive source is inserted through a catheter. Dr. Herman Kattlove, a medical oncologist and spokesman for the American Cancer Society, also counsels patience until more is known about partial-breast irradiation's long-term effectiveness. "We're concerned that [partial-breast irradiation] hasn't been proven," he says. "It's too early to tell" if it will bear out as a treatment as effective as whole-breast irradiation. "I would recommend caution," he says. "We're awaiting results of [the ongoing] clinical trials," he adds. "We need to have that data." Freedman concurs. "Standard treatment is certainly [irradiating] the whole breast," he says. If women want to try the partial-breast irradiation treatment, he adds, they should do it in an approved clinical trial. "We're not against clinical research," Freedman says. "What I don't like is, women are being given this [treatment] outside of clinical studies." This year, more than 200,000 people in the United States will get a new diagnosis of breast cancer, according to American Cancer Society estimates, and more than 40,000 are expected to die from the disease.

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Letrozole May Cut Risk of Breast Cancer-(ET-23/10/2003)

Health officials recently halted a large international study after an early review of the results suggested that the anti-estrogen drug letrozole dramatically reduces the risk of recurrence of cancer among of breast cancer survivors. About 211,300 new cases of breast cancer are expected to be diagnosed this year in the United States, two-thirds of them in women who have gone through menopause. Most tumors will be estrogen-receptor positive, meaning that the hormone fuels their growth. The standard treatment for breast cancer is surgery, radiation and/or chemotherapy, followed by five years of tamoxifen, which helps keep estrogen from entering cells. Research has shown, however, that women gain no additional benefits after they take tamoxifen for five years, and that it may increase women's risk of endometrial cancer, pulmonary embolism, and stroke.

The study, led by Dr. Paul Goss of Toronto's Princess Margaret Hospital, involved 5,187 women at hundreds of medical centers in the United States, Canada and Europe. Half the women in the study were randomly assigned to take letrozole. The others took placebo pills. An average of 2.4 years after their tamoxifen treatment ended, 132 (13 percent) women who were taking placebos developed new breast cancer or recurrences of their original cancer, compared with 75 (7 percent) among women taking letrozole who had a recurrence. The study was supposed to follow the women for five years after they had finished with tamoxifen treatments, to see if letrozole was better than a placebo during that period. But when an independent committee reviewed the results early, the treatment was deemed so successful that the study was immediately halted and it was decided that all the women taking part in the study should be given the drug.

Letrozole, made by Novartis and sold under the trade name FemaraŽ, is one of a new group of anti-estrogen medications called aromatase inhibitors. The other aromatase inhibitors currently on the market are anastrozole, which AstraZeneca sells as ArimidexŽ, and exemestane, which Pfizer sells as AromasinŽ. Aromatase inhibitors work by stopping production of estrogen by blocking the enzyme aromatase, which converts other hormones into estrogen. Therefore they are not seen as entirely benign -- because these drugs hinder estrogen production at its source, they may reduce blood levels of estrogen by 95 percent or more. This also raises the risk of osteoporosis and can cause hot flashes and night sweats. The study results, along with two editorials, will be published in the November 6, 2003, issue of The New England Journal of Medicine, but the journal published them early on October 9 because of their importance.

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Researchers Pinpoint Genes' Role in Breast Cancer-(HealthDayNews-23/10/2003)

Women who carry the BRCA1 or BRCA2 gene mutation have an 82 percent risk of developing breast cancer by the time they are 80 years old. The silver lining is that even those with the highest genetic risk can stave off the disease with exercise and maintaining a healthy weight when they're younger, says a study in the Oct. 24 issue of Science. "[The study authors] have characterized probably as best as can be done to date the incidence and risk of developing breast cancer if you fit into this particular group of women," says Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. "These can be used as guidelines now. They are probably the best and most accurate guidelines that we have to date."

Past risk estimates for women with one of the mutations ranged from 25 percent to 80 percent, but generally focused on women who had a strong family history of breast cancer. "We wanted to see what was the likelihood of carrying the mutation regardless of family history," says Jessica Mandell, the primary genetic counselor for the study. Mandell, who is with the Human Genetics Graduate Program at Sarah Lawrence College in Bronxville, N.Y., was also the study's research coordinator and a co-author.

Mandell and her colleagues looked at 1,008 Ashkenazi Jewish women with invasive breast cancer who were part of the New York Breast Cancer Study Group. This is an ethnically homogenous group and the mutations, if present, could be expected to be found in specific areas of the BRCA1 and BRCA2 genes. "In the general population, you would have to look at the entire gene sequence, which is a much more complicated process," Lichtenfeld explains. "By selecting Ashkenazi Jews, they were able to hone in on a couple of places on the gene where you would expect to find an abnormality." The researchers found the lifetime risk of ovarian cancer for women with the BRCA1 mutation was 54 percent and, for women with the BRCA2 mutation, 23 percent. They also found that women born before 1940 had a lower risk of breast cancer than women with the mutation who were born after 1940, strongly suggesting that environmental factors are also at play here. Women who had had a healthy weight and who exercised when they were adolescents had a lower risk.

Overall, about 10 percent of the group (104 women) carried the BRCA1 or BRCA2 mutation. The risk in this group of developing breast cancer by the age of 40 was 20 percent; by the age of 60, 55 percent; and by the age of 80, 82 percent, the researchers found. There were other startling differences in breast cancer risk. Women carrying one of the mutations who were born before 1940 had a 24 percent risk of developing breast cancer by age 50. Among those born later, however, that risk jumped to 67 percent. "This has broad implications because it means that there are other factors that are occurring in the general population that are accounting for increased incidence of breast cancer," Lichtenfeld says. Based on their findings, the researchers speculate that all women could help reduce their risk of breast cancer by being physically active and maintaining a healthy weight during adolescence. Significantly, half of the women with a mutation did not have a history of breast cancer in their immediate family.

"We certainly expected to find some women who didn't have a family history but we didn't necessarily predict it would be an equal 50/50 split," Mandell says. "There are a lot of things that can mask the genetic mutation being passed on, for example, inheritance through men in the family, small family size or few women in the family." What this means is that genetic screening may be appropriate for more women than originally thought. Certainly, if you have a family history of breast cancer you might consider being tested. In addition, age, ancestry and factors such as weight, exercise patterns, tobacco use, age at first menstruation and exposure to hormones need to be taken into account, the researchers say.

The results of a second study, this one appearing in the Oct. 23 issue of Breast Cancer Research, may provide another reason for testing for certain women. This study found that women with the BRCA1 mutation have a poor long-term survival when they develop breast cancer. Chemotherapy, however, can mitigate this effect. Any decisions having to do with genetic testing and treatment need to be discussed with your physician

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Pushing Breast, Cervical Cancer Screenings-(HealthDayNews-28/10/2003)

An extended media campaign and efforts by community volunteers to promote regular screenings for breast and cervical cancer increased the likelihood that younger Hispanic women in San Antonio, Texas, would get a Pap smear. So says a study in the current issue of the American Journal of Public Health. Researchers found the media blitz and community programs resulted in a large increase in the rates of Pap smear screening tests among Hispanic women aged 40 and younger in San Antonio compared to their counterparts in Houston, where there was no such campaign. But the public health education efforts in San Antonio did not affect Pap smear screening rates among women older than 40 and didn't greatly change the rates of mammogram screening for any of the women.

The study also found older women were least likely to have been screened for cancer, along with those who spoke only Spanish, who belonged to lower-income families, and those with little formal education. Previous research has shown that Hispanic women are less likely than white women to be screened for cancer. The San Antonio campaign to promote screening was designed specifically for Mexican-American women. It included print, radio and television ads in both Spanish and English. In addition, neighborhood volunteers were trained to conduct face-to-face visits to encourage women to get screened.

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Exploring Environmental Causes for Breast Cancer-(HealthDayNews-23/10/2003)

Four new Breast Cancer and the Environment Research Centers in the United States will receive $35 million over the next seven years from the National Institute of Environmental Health Sciences and the National Cancer Institute. The new centers are at the University of Cincinnati, Fox Chase Cancer Center in Philadelphia, the University of California, San Francisco, and Michigan State University. The four centers will collaborate in several areas. Using animals, they'll study the development of mammary tissue and the effects of specific environmental agents. They'll also enroll young girls from different ethnic groups and study their life exposures to a number of environmental, nutritional and social factors during puberty. Each center will also specialize in certain areas of research. For example, the University of Cincinnati will investigate factors that influence the decline in age of onset of menstruation and identify improved early markers for cancer susceptibility. In addition, all the centers will work with advocacy groups to incorporate their insight and experience into the research effort.

"Although diagnosis and treatment are improving, breast cancer is the leading cancer in women," Dr. Elias A. Zerhouni, director of the U.S. National Institutes of Health, says in a prepared statement. "To improve this picture, we need to better understand the elusive environmental piece of the breast cancer puzzle. If we can understand the early events that can set the stage for breast cancer, we can do more to prevent this disease," Zerhouni says.

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Fruits, Veggies Cut Breast Cancer Risk-(HealthDayNews-31/10/2003)

A diet rich in fruits and veggies can help protect against breast cancer. A study by Oregon Health and Science University researchers found women who eat at least four servings of fruits and vegetables have a 50 percent lower risk of breast cancer than women who consume no more than two such servings each day. They reached that conclusion after examining the diets of 378 women with breast cancer and the diets of 1,070 cancer-free women. All the women, living in Shanghai, China, filled out questionnaires that asked about their intake of 108 individual food items, fried and restaurant food, dietary changes, and the use of nutrient supplements and Chinese herbal medicines. Along with its finding about the cancer benefits from eating more fruits and vegetables, the study also found that eating at least six eggs a week was also associated with reduced risk of breast cancer. But no association was found between intake of soy or soy products and breast cancer risk.

The study was presented this week at the American Association for Cancer Research conference in Phoenix. "This study provides further evidence that low fruit and vegetable intake in the Western diet may be a major risk factor in developing breast cancer," lead author Jackilen Shannon, an assistant professor of public health and medicine, says in a prepared statement. "Women should modify their diet to include more fruits and vegetables to help prevent breast cancer," Shannon says

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Risks Higher for Some Young Cancer Patients - Study-(Reuters-03/11/2003)

Young women with breast cancer who have breast-conserving surgery should be monitored carefully for many years because they have a higher risk of recurrence than older patients, researchers said. Doctors at the Institute Gustave-Roussy and INSERM in Villejuif, France, report the finding from a study comparing 88 breast cancer patients who underwent a lumpectomy plus radiation therapy with 91 women who had a mastectomy. The women were followed for an average of 22 year. "What we found in the trial of 179 patients was that there was no difference over time on survival or on metastasis (spread beyond the breast)" between the lumpectomy and mastectomy groups, said Dr. Rodrigo Arriagada, who headed the research team.

The risk of the cancer reappearing was five-fold less in breast-conservation patients than in other women who had a mastectomy during the first five years after surgery. "However, after five years it was 12-fold greater," Arriagada said. He and his colleagues said that while the age range for those who experienced early recurrence was similar in the two groups, a late recurrence of the disease was more common in women who had breast-conserving surgery and who had been 40 years old or younger when they were first diagnosed with the illness.

Arriagada and his colleagues, who report their findings in the journal Annals of Oncology, said all the women in the study had been diagnosed in the 1970s and so none had been given the drug tamoxifen, which is now a standard treatment for women with hormone-sensitive tumors. "If these results are corroborated, younger patients should be informed of the higher risk of local recurrence and the need for indefinite follow up if they choose conservation treatment," Arriagada said in a statement. But the researchers stressed that despite the higher risk of a recurrence, the overall survival of women who had both types of surgery was the same.

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Studies Look Beyond Genes for Breast Cancer Risk Factors-(ET-29/10/2003)

While significant gains have been made in detecting and treating breast cancer and the death rate is on the decline in the US, scientific research has not yet found the major causes of the disease. Now, well-designed population studies will search for answers in women's environments and lifestyles. Researchers will look beyond the genes known to cause a small sliver of breast cancer cases to factors such as nutrition, exercise, chemical exposures, as well as home and work environments. The National Institutes of Health (NIH) recently announced funding of four new Breast Cancer and the Environment Research Centers to study environmental factors throughout a woman's life that might increase her risk of developing the disease. "Although diagnosis and treatment are improving, breast cancer is the leading cancer in women," NIH director Elias A. Zerhouni, MD, said. "To improve this picture, we need to better understand the elusive environmental piece of the breast cancer puzzle. If we can understand the early events that can set the stage for breast cancer, we can do more to prevent this disease."

In one collaborative project, the centers will use animals to study the development of mammary tissue and the effects of specific environmental agents. Another project will enroll young girls of different ethnic groups and study their life exposures to a wide variety of environmental, nutritional, and social factors that impact puberty. Early puberty has been shown to increase breast cancer risk later in life. The four centers are the University of Cincinnati; Fox Chase Cancer Center in Philadelphia; the University of California, San Francisco; and Michigan State University in East Lansing. The centers will receive funding from the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute, both agencies of the NIH, amounting to $5 million a year over seven years. In addition, the centers will work with advocacy groups, including the American Cancer Society, who will play a part in outreach activities to translate the results of the research into improved understanding, diagnosis, and prevention of breast cancer.

The National Institute of Environmental Health Sciences is also currently recruiting the sisters of women who have had breast cancer to study hereditary and environmental risk factors for the development of the disease. The Sister Study is the first long-term study of its kind. It will enroll 50,000 US women from diverse racial, ethnic, and socioeconomic backgrounds, all of whom have a sister who has or had breast cancer. Sisters of women with breast cancer, on average, have a higher risk of developing the disease than women who don't have a sister or mother with breast cancer. The significance of studying sisters lies in the fact that, beyond sharing genes, sisters are also more likely to have been exposed to the same environments early in life and often have similar lifestyles as adults, which provide investigators opportunities to study the factors that can lead to breast cancer.

Studying the impact of the environment on breast cancer has been challenging. Generally, researchers have not had much information about which potentially harmful exposures may lead to breast cancer. The Sister Study hopes to change that by collecting detailed exposure information from women who have not developed the disease. The researchers will measure chemical levels in blood, urine and toenail samples, and even in samples of household dust. The study will collect data annually from women over a 14-year period, and is currently enrolling women in the US between the ages of 35 and 74 with a full or half-sister who has or had breast cancer. The study only seeks women who have not had breast cancer.

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New agony over breast cancer-(USA TODAY-10/11/2003)

Women dread breast cancer perhaps more than any disease, and news coverage about the latest study of breast cancer genetics ratcheted up that anxiety a notch or two. Scientists reported that Jewish women with little family history of the disease could be carrying a genetic mutation that virtually assures they'll get it. As a result, some healthy women - Jewish and non-Jewish - with no relatives who have had breast cancer are wondering whether they might be carriers. Despite appearances, though, only 5% to 10% of the 211,000 breast cancer cases that will be diagnosed in the USA this year will arise from an inherited mutation. About one out of 40 Jews of eastern European descent are thought to carry a mutation in one of the two known breast cancer genes, BRCA1 and BRCA2. In the general U.S. population, only one in 800 to one in 400 people carry a mutation in either of the genes, which also raises the risk of ovarian cancer.

The new study, which is published in the Oct. 24 issue of Science, focused on breast cancer patients who, like most American Jews, were of Ashkenazi, or eastern European, descent. If they carried a mutation, researchers tested as many of their adult relatives as possible. Carriers' offspring have a 50-50 chance of inheriting the mutation. Half of the 104 patients with mutations had no breast or ovarian cancer among mothers, sisters, grandmothers or aunts. In nearly all of these cases, the patients had inherited mutations from their fathers, and breast cancer is rare in men. Often, their sisters and aunts had won the genetic coin toss and inherited normal versions of BRCA1 and BRCA2. The researchers found that women with a BRCA1 or BRCA2 mutation have more than an 80% lifetime chance of developing the disease. They also have a high lifetime risk of developing ovarian cancer: 23% with a BRCA2 mutation, 54% with BRCA1. And, the scientists say, breast cancer risk in non-Jewish carriers of BRCA mutations is equally high.

"For women, that's scary, even if the reality is it probably doesn't apply to them," says Rochelle Shoretz, founder of Sharsheret, a national organization for young Jewish women dealing with breast cancer. Shoretz, 31, who was diagnosed with breast cancer at 28, says she has been receiving a number of calls because of the latest study. Some callers are Jewish and some aren't, but all either know they are carriers or are worried they might be. "We know that you can be at a higher risk even with a lower family history, and that's something that really wasn't considered before," says study co-author Jessica Mandell, a genetics counselor and research coordinator at Sara Lawrence College and the University of Washington. In breast cancer patients of any ethnic background, Mandell says, the younger they are, the greater the chance that an inherited mutation might be involved. Shoretz sought testing right after her diagnosis, even though only her father's mother had had the disease, and it was found when she was much older. If Shoretz was a carrier, she planned to have a double mastectomy. Even healthy carriers sometimes choose to have their breasts and ovaries removed to cut their cancer risk. "I ultimately tested negative, which was a little bit of a surprise to me," says Shoretz, of Teaneck, N.J. So she had a lumpectomy.

Although the new study doesn't discuss testing all Ashkenazi Jewish women for BRCA mutations, an accompanying editorial in the journal does raise that possibility. Georgetown University Hospital genetics counselor Beth Peshkin says the new study drove dozens of Jewish women with little family history to call the referral line for breast cancer genetics research at her institution. "If this provides the impetus for people to collect their family history and to make a call to get more information, then that's a good thing," she says. "My hope is that not everybody runs out and gets tested." There's a danger that testing negative for a BRCA mutation will give women a false sense of security, Peshkin says. Women with a negative test still have the same one-in-eight lifetime risk as the general population - perhaps even higher if they have a family history.

Breast cancer genetics researchers have focused on Ashkenazi Jews because nearly all of their inherited breast cancer cases arise from one of three ancient "founder" mutations, two in BRCA1 and one in BRCA2. In most other women, though, inherited breast cancers stem from BRCA1 or BRCA2 mutations unique to a family. So far, hundreds of different mutations have been identified. Theoretically, there could be thousands. "The question of screening is not realistic for American women generally," says University of Washington geneticist Mary-Claire King, lead author of the recent study. "It's too expensive. There's too much chance a mutation would be missed." Though the test for the Ashkenazi mutations costs a few hundred dollars, the test for mutations in the entire BRCA1 and BRCA2 genes costs nearly $3,000. Insurance usually covers the cost in women who have an elevated risk of being carriers.

Even among Ashkenazi women whose family history suggests a high likelihood of a mutation, many decide not to get tested, says Kenneth Offit of Memorial Sloan-Kettering Cancer Center in New York. "The major barrier for women in our clinic to be tested is not the cost, is not the uncertainty, is not the fear of interventions," says Offit, discoverer of the most common Ashkenazi mutation. They're worried they'll lose their health insurance, although none tested at his clinic has, he says. To help assuage Americans' concerns, the Senate passed a bill last month that would prohibit insurance companies from using genetic information or family histories to deny coverage or set premiums. The measure also would prohibit employers from using such information in hiring or firing. The health insurance industry has argued that the legislation would increase costs without improving consumer protection

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Radiation Therapy Underused for Breast Cancer-(Reuters Health-12/11/2003)

The great majority of women with breast cancer should get radiation therapy at least once during the course of their illness but, in reality, relatively few actually do That's the finding from an Australian study, by Dr. Geoff Delaney and the Collaboration for Cancer Outcomes Research and Evaluation team based at Liverpool Hospital in Sydney. In comments to Reuters Health, Delaney noted that radiation therapy is "an essential mode of cancer treatment and contributes to the cure or palliation of many cancer patients." Making sure radiation treatment is available for patients who need it "requires a rational estimate of need." To that end, Delaney's group used guideline-based evidence as well as epidemiologic data to calculate the number of breast cancer patients who should receive radiation. The "ideal utilization rate" turned out to be 83 percent, the researchers report in the November 1st issue of the journal Cancer.

By comparison, actual radiation therapy utilization rates for breast cancer over the last decade in Australia and internationally were substantially lower-- between 24 percent and 71 percent. Possible reasons for the shortfall in delivery of radiation therapy include lack of access, inadequate referral, refusal of treatment by patients, or, as the authors acknowledge, incorrect data on optimal or actual utilization rates. "The implications of our findings are that we now have an estimate of the correct number of cancer patients who require radiation," Dr. Delaney said. "This provides us with a way for planning radiation therapy services in a more reasonable fashion. It also allows us to assess the actual rates of radiotherapy use and to identify areas or specific cancer conditions where radiotherapy use could be improved." Delaney also told Reuters Health that this paper has generated "significant interest by radiation oncology centers in Canada and the United Kingdom as this is the first completed study of its type in the world."

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Waist-to-hip ratio good survival predictor in women with breast cancer-(CP-12/11/2003)

Post-menopausal women with breast cancer have a better chance of surviving if their waist-to-hip ratio is low, meaning they aren't carrying a lot of fat around their midriffs, a study from the British Columbia Cancer Agency suggests. Researchers followed breast cancer patients for a period of 10 years to test the theory that women who have higher amounts of stomach fat are at greater risk of dying from the disease. They found that those with the highest ratio - in other words, the women who were heaviest around the middle - were three times more likely to die from breast cancer than those with the leanest torsos. "The risk in the highest group compared to the lowest is three-fold greater. So the apples are at three-fold greater risk of dying in the first 10 years than the pears were," lead researcher Marilyn Borugian said in an interview.

The fruit terms refer to women who carry excess weight around their midriff - apples - versus women who are pear-shaped, with smaller waists and larger hips. The increased risk was only found among women with breast cancer who had gone through menopause and who had tumours that were estrogen fuelled, according to the study, which will be published later this month in the American Journal of Epidemiology. Borugian and her colleagues enrolled 586 women with newly diagnosed breast cancers in their study in 1991-92, following them for at least a decade. During that period 112 of the women died from breast cancer. While those in the highest group had the highest risk, Borugian said the chances of not surviving seemed to rise "faster than you would have anticipated" among women whose ratio - calculated by dividing the hip measurement into the waist measurement - was higher than 0.75. In fact, with every one-point increase in the ratio - going from 0.8 to 0.9, for example - the mortality risk rose by 40 per cent.Many publications suggest 0.8 is the point at which health risks caused by abdominal fat seem to kick in, but Borugian said this work suggests women might be better off if they could stay below 0.75.

It's been known for awhile that people who put on weight around their middle are at higher risk of developing a number of diseases - heart disease and diabetes among them. "You see the person with the kind of skinny hips, no bum, skinny legs - and a gut? This is a risk," Borugian said. "Despite the fact that overall in terms of the poundage they're carrying, it might not be as much as someone else or it may be the same as someone else, the fact that it's located around the middle is a sign of a metabolic imbalance. And it is an increased risk."

Why? Experts aren't positive, but they have some clues. Fat produces estrogen, which fuels growth of estrogen-positive tumours. And excess abdominal fat is a sign of insulin resistance; research increasingly suggests this condition plays a function in breast cancer. People with insulin resistance actually produce more circulating insulin to counteract the problem; insulin stimulates estrogen production. Borugian's area of expertise is modifiable lifestyle risk factors related to breast cancer. She wanted to do the study to see if there is something women could do to improve their chances of surviving the disease. "My interest was: well, what are the things that might lead to information that women and doctors can actually use to improve their lives. Because you can't change your age, and you can't change the (cancer) stage you are at when you discover your cancer," she explained. "If I were diagnosed, I'd like to know: Well, what can I do?"

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Early Detection the Key to Combating Breast Cancer-(HealthDayNews-10/10/2003)

Breakthrough treatments for breast cancer, such as injecting antibodies that track down and kill aggressive cancer cells, often grab the headlines and the public's attention. But when it comes to detailing the progress in the war on beast cancer, the real star is early detection. That's a message that bears repeating in October, National Breast Cancer Awareness Month. "Two thirds of the progress is early detection," says Robert Smith, an epidemiologist and director of cancer screening for the American Cancer Society. What else has helped to reduce the breast cancer death rates, which have been declining since 1989? "Women responding to symptoms faster and incremental improvements in treatment," Smith adds.

Nearly 212,000 new cases of breast cancer will be discovered in the United States this year, according to American Cancer Society predictions, and more than 40,000 women will die of the disease. "The recommendations for annual mammograms [for women age 40 and older] are very important," Smith says. "Most doctors' offices have reminder systems. If they don't, ask for them, or find a way to mark the calendar so you'll remember, such as getting it the month of your birthday." In recent years, debate has flared over the role and value of regular screening mammograms, with some researchers finding that such tests have little or no lifesaving value. But more recent studies have demonstrated their worth. Why the discrepancy?

Authors of more recent studies say the older analyses that claimed the exams had no life-saving value were scientifically flawed. In its new guidelines, issued earlier this year, the American Cancer Society stands firm in its recommendation that women age 40 and older get annual mammograms. Also crucial for breast health, the society says, is a clinical breast exam done by a health professional every year for women 40 and older, and approximately every three years for women in their 20s and 30s. While previous guidelines recommended monthly breast self exams, the new guidelines make these optional. The reason? A lack of research showing the exams can reduce deaths from breast cancer, but a reluctance on the part of the society to discourage the practice, since it can make women more familiar with their breasts and alert to changes.

But even a woman who follows the mammography screening recommendations might not be home free, says Dr. John Glaspy, a professor of medicine at the University of California, Los Angeles' Jonsson Cancer Center. "Most of the things that drive a woman's risk [of breast cancer] are out of her control," says Glaspy, referring to genetic abnormalities such as the BRCA1 or BRCA2 genes that increase breast cancer risk. "In general, it is not a lifestyle cancer."Besides following the screening guidelines, a woman can eat a low-fat diet, although Glaspy says that's not proven to reduce breast cancer risk. "Eat for your heart [a low-fat diet] and that's probably the best you can do at this point for breast health."

Regular physical activity has also been linked with a lower risk of breast cancer. At midlife, a woman can do one more thing to reduce her risk, Glaspy suggests -- avoid hormone replacement therapy. "If a woman is taking estrogen and has the absolute desire to lower her breast cancer risk, she shouldn't be taking estrogen," he says. If a woman does get breast cancer regardless of close attention to screening, some of the latest treatments may help. For instance, Herceptin, a monoclonal antibody given intravenously, targets cancer cells that make too much of a protein and can help a woman with metastatic breast cancer survive longer. The future will bring more of these targeted treatments, Glaspy predicts. "More targeted therapies are being looked at, particularly in combination with Herceptin," he says. Advances in screening are progressing, too, Smith says. Methods that look promising, he says, include digital mammography, in which the image can be manipulated so specific areas of the breast can be examined more carefully.

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New Drug May Prevent Breast Cancer Recurrence-(ET-10/10/2003)

There may soon be a new powerful weapon against recurring breast cancer. NewsCenter 5's Liz Brunner reported that a report in an upcoming New England Journal of Medicine shows an existing drug can pick up where tamoxifen leaves off. Letrozole is a drug currently used when breast cancer spreads. Preliminary results from a large study of women with early stage disease were so impressive that the new study was stopped and the information was being released so doctors can tell their patients about it.

If a woman takes tamoxifen after a battle with the most common type of breast cancer, she cuts in half the chance it will come back. But the benefits last only five years. "At the end of five years, women often wonder what they should take next, and to date the recommendation has been for nothing further," Dana Farber Cancer Institute Dr. Harold Burstein said. Enter Letrozole, also called Femera. It's an estrogen suppressor currently used to treat late-stage breast cancer. Research on more than 5,000 postmenopausal women with early stage cancer shows when Letrozole was taken following five years of tamoxifen therapy, it further reduced the chance of recurrence by 43 percent over the next three years. "We all expected there would probably be some advantage in taking Letrozole over placebo, but the size of the difference and how quickly it occurred is the striking aspect of this trial," Beth Israel Deaconess Medical Center Dr. Steve Come said.

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Doctor Tests Gold in Fighting Cancer-(AP-13/10/2003)

An Arkansas doctor is trying to find a safe and efficient way to target cancerous cells using flecks of gold that are only nanometers wide. It could set a new standard for breast cancer therapy. Dr. Vladimir Zharov, a biomedical engineer and director of laser research at the University of Arkansas for Medical Sciences, won a $106,500 grant from the U.S. Department of Defense Breast Cancer Research Program, to study the treatment concept. The concept is still unproven, but preliminary tests have shown the gold "nanoparticles" could interact with laser radiation to destroy only the targeted cells, without collateral damage to healthy cells, Zharov said.

Several teams of researchers around the world are looking at similar concepts. Gerald Diebold, professor of chemistry at Brown University, said chemists and medical researchers are scrambling to find ways to improve on the current X-ray and ultrasound technology used to diagnose tumors. "A mammogram is a mess of lines. ... It's so hard to see any gradations until the tumor is already metastasized," he said. "But we've known about gold's absorption for a long time and I think we're making very nice progress." Once attached to tumor cells, the gold absorbs laser light far more thoroughly than anything else, which makes it ideal for diagnostic imaging of small, hard-to-detect tumors. And the laser's destructive power also could be harnessed to attack cells with gold marks on them without so much as cutting into the breast.

Alexander Oraevsky of Fairway Medical Technologies in Houston, who patented an elongated gold particle that appears to absorb laser light best, said scientists are still years away from figuring out the best way to deliver the gold markings to tiny clusters of tumor cells, without hurting a patient. "This is a very hot area, and nanotechnology in association with lasers is very big," Oraevsky said. "But the major question remains: Can the nanoparticles be delivered specifically to cancer in a human body sufficiently and efficiently?" Zharov said he thinks he can create a smarter delivery system through his research. He and Dmitri Lapotko of A.V. Luikov Heat and Mass Transfer Institute in Minsk, Belarus, spent years in Russia studying how gold could be used to create clearer diagnostic images. But when the laser beam was strengthened, Zharov realized the nanoparticles could go "from markers to killers." He calls his concept "magic gold atomic bullets." Zharov said laser light interacts with gold particles and creates heat and sound waves that make the gold explode, and he expects that the mini-blasts will destroy only the marked tumor cells, not the healthy breast tissue cells. He said he will use the federal grant over the next year for in-vitro tests on rats to pinpoint ideal temperatures, to find the best ways to deliver the gold to tumor cells and to ensure that healthy cells are never affected. To this point, tests have been limited to dead samples under a microscope.

Zharov's pursuit is hardly novel. The concept of absorption and light scattering inside a spherical object is nearly 100 years old, said Oraevsky, a former University of Texas biomedical engineer. He worked for the last decade using lasers as "optical tweezers" to safely remove malignant tissue. He credits his colleagues at Rice University, Naomi J. Halas and Jennifer West, with designing nanoparticles for treatment of tumor cells. The problem will be in receiving approval for human tests, Diebold said. Current research will determine how long that will take. Last year, Halas and West received a multimillion-dollar award from the U.S. Army Medical Research and Materiel Command, and Oraevsky received a $1 million grant from the National Institutes of Health.

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Is Pregnancy After Breast Cancer Safe?-(ET-12/10/2003)

Is it safe to get pregnant after having breast cancer? A recent study by researchers at the Fred Hutchinson Cancer Research Center in Seattle, Washington, suggests it is. But other breast cancer experts say the findings in the new report, published in the journal Cancer (Vol. 98, No. 6: 1131-1140), need to be interpreted with caution The Hutchinson researchers, led by Beth Mueller, PhD, found that young women who survived breast cancer then subsequently had children did not have a greater risk of dying from breast cancer. The findings are in line with those of previous studies, and should reassure women who want to start a family or have more children after a diagnosis of breast cancer, said Mueller, a member of the Public Health Sciences Division at the Hutchinson center. "This is such an important thing in a woman's life experience and in her family's experience," Mueller said. "It's important for young women faced with this question to know."

But breast surgeon Jeanne Petrek, MD, says the new study doesn't provide solid answers for women. "We certainly don't know if pregnancy after breast cancer treatment is safe," explained Petrek, director of the Evelyn H. Lauder Breast Center at Memorial Sloan-Kettering Cancer Center. She said the weak design of this study and of previous research on the subject makes it impossible to draw any firm conclusions about how pregnancy might affect a breast cancer survivor.

Mueller and her colleagues identified more than 15,000 women under age 45 in Seattle, Detroit and Los Angeles who were diagnosed with invasive breast cancer. Of those, 438 women gave birth some time after being diagnosed. The researchers compared each of these women with up to 12 women of similar age and race with breast cancer who had not given birth. Women who gave birth 10 months or longer after diagnosis (that is, they were not pregnant when they found out they had breast cancer) had almost half the risk of dying from breast cancer, compared to women who did not have a child after diagnosis. Reduced risk was seen even among women whose disease had spread to the lymph nodes, or who had tumors larger than two centimeters. But women who were already pregnant at the time their breast cancer was found did not have a lower risk of dying, and in some cases had a greater risk.

To some extent, Mueller said, the seemingly protective effect of pregnancy may be due to a phenomenon called the "healthy mother bias" -- only women who feel healthy after breast cancer treatment are likely to try having a child. The researchers did not have information about the women's health status when the pregnancy occurred, so they couldn't determine whether the healthy mother bias played a role in their findings. However, Mueller said the evidence showed that pregnancy did not seem to increase the risk of dying from breast cancer. "That's the main message: We didn't see an increase in risk," Mueller said. That finding is consistent with the results of previous studies, she said. But Petrek said the healthy mother bias is a "fatal flaw" in both this and previous research. Only a woman whose breast cancer has not recurred would be likely to attempt a pregnancy, she said.

Because the researchers had no data on cancer recurrence from any of the women, there's no way to know whether the women in the comparison group (those who did not get pregnant) had already had a recurrence - and thus were sicker than their pregnant counterparts, and perhaps more likely to die. "I think they're really overstating it," said Petrek, who is a member of the ACS breast cancer advisory board.

Breast cancer is relatively rare in young women; more than three-quarters of cases occur in women over age 50. In 2003 the American Cancer Society estimates that about 11,500 US women under age 40 will develop invasive breast cancer, and 1,400 will die from it. As improved treatments help more young women survive breast cancer, the question of whether to have a child later becomes increasingly important. "Until about a decade or so ago," Mueller said, "the conventional thought was that young women who had survived breast cancer probably shouldn't get pregnant, or should wait a few years before getting pregnant." Indeed, many doctors still advise a waiting period. "We tell patients to wait two years if they have negative [lymph] nodes, and five years if they have positive nodes, so that the really aggressive disease will become known before they get pregnant," Petrek said. This is particularly important for young women, who are more likely to have aggressive breast cancer.

Although few studies have been done, none have found evidence that pregnancy after successful breast cancer treatment increases the risk of the disease coming back. Mueller noted that two previous Scandinavian studies also have found no increased risk of dying in breast cancer survivors who go on to have children. But Petrek noted that breast cancer is strongly influenced by hormones and that it is "intuitive" that the changing hormone levels during pregnancy could have some effect on a woman who has already had the disease. Petrek said the type of research that needs to be done to learn more about the risks of pregnancy for breast cancer survivors are long-term studies that follow women from the time of diagnosis, through treatment and any subsequent pregnancy, and then for a substantial period afterward. Such research could take 10 years or more, she said. She is currently recruiting patients for just this type of study. Mueller also called for further research to determine what risk pregnancy may pose to breast cancer survivors, and if that risk is influenced by factors like age, race, or disease characteristics.

Petrek and Mueller both said breast cancer survivors who are thinking about getting pregnant need to discuss the issue thoroughly with their families and their doctors. Women should talk to their doctors about their breast cancer prognosis including the chance of having a recurrence, Petrek said. And they need to think about what kind of waiting period is appropriate because of the risk of relapse. Women should also talk to their doctors about other health problems related to breast cancer treatment - heart damage from chemotherapy drugs, for example - that could be exacerbated by pregnancy. Survivors and their families also need to consider how they would manage if the breast cancer were to return, said Petrek. In the end, the decision is a very complex and personal one. "Every woman is different, and every situation needs to be tailored," said Mueller.

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New Tumor Gene Test May Help Fight Breast Cancer-(Reuters-25/09/2003)

Testing tumors in women with breast cancer for the BRCA1 gene could increase the effectiveness of chemotherapy dramatically, researchers said. In laboratory tests, scientists from the Cancer Research Center, Queen's University Belfast, found tumor cells reacted very differently to anti-cancer agents depending on how well the gene was working within them. A functioning BRCA1 gene made cells more than 1,000 times more sensitive to drugs like Taxol and Taxotere that work by blocking the final stage of cell division. But the same cells were between 10 and 1,000 times more resistant to drugs like cisplatin that work by damaging DNA within tumors. "Essentially, cancer cells with functional BRCA1 are highly resistant to one type of chemotherapy but extremely sensitive to another," said senior researcher Paul Harkin. "It's very exciting, because knowing a tumor's BRCA1 status may be invaluable in deciding which type of chemotherapy to use."

The BRCA1 gene plays an important role in stopping cancer developing, and it has long been known that women who inherit a damaged version of the gene have a high risk of developing breast cancer. But BRCA1 may also get switched off in as many as 30 percent of tumors, even in patients who inherited a normal version of the gene. Unlocking the genetic reasons why some cancer patients respond to treatment while others do not is a central goal of medical research. Some progress has already been made, with Genentech Inc.'s Herceptin, for example, reserved for patients whose tumors over-express the HER2 gene. But Harkin said many more such markers were needed to make cancer treatment more effective. "This is the challenge for oncology over the next few years. We have lots of really good drugs now. The problem is we need to know why one patient responds and another patient with an apparently identical tumor does not," he told Reuters in a telephone interview. Harkin and colleagues plan to conduct a clinical trial over the next two years to confirm their laboratory findings. They will assess the effectiveness of Aventis SA's Taxotere in breast cancer patients whose tumors show differing BRCA1 levels.

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HRT Builds Bone, But That's Not Benefit Enough-(HealthDayNews-30/09/2003)

Hormone replacement therapy does in fact help prevent broken bones, but this benefit doesn't outweigh the catalogue of risks that bedevil the troubled regimen, new research shows. The work is the latest in a series of studies that have found hormone replacement therapy (HRT) simply isn't worth the trouble it can cause, at least for most women. The latest results, reported in the Oct. 1 issue of the Journal of the American Medical Association, come from an arm of the Women's Health Initiative study looking at the effects of the combination of estrogen and progestin. Pairing the two guards against the small risk of uterine cancer associated with estrogen alone. That trial was halted in July 2002, three years early, when researchers discovered a small but significant increase in the risk of breast cancer in women taking the two hormones. They concluded the benefits of the therapy, most notably its ability to prevent fractures, didn't outweigh the cancer risks, which also included more heart attacks, strokes and lung clots.

HRT is a proven bone-builder. As a result, it has been used for decades for the prevention and treatment of osteoporosis, a condition that puts 10 million Americans at high risk of fractures. That history raised this question: Are there some women whose risk of broken bones -- and especially hip fractures -- is so high that taking HRT makes sense? The new study suggests the answer is no. "We did not see any evidence that there was a sub-group of women at high risk of fracture for whom the benefits" of HRT are substantial enough to ignore the perils, says study author Jane A. Cauley, a bone expert at the University of Pittsburgh. The 8,500 women taking the hormones gained much more bone mass, a plus for skeletal strength, than the 8,100 taking dummy pills in the WHI study. And their risk of fractures was about 25 percent lower than that of the other women. But women at the highest risk of breaking a bone during the study didn't get more benefit from HRT than those at the lowest risk -- while enduring the same odds of suffering a heart attack, stroke, breast cancer or other serious adverse effect. Because the women were healthy when they began the study, those risks don't seem worth taking, Cauley says, adding, "We're trying to keep people healthy and prevent chronic disease."However, Cauley warns women taking HRT for their bones to consult their doctor before stopping the drugs abruptly. Doing so can accelerate bone loss -- by up to 5 percent a year -- she says. A variety of alternative drugs for osteoporosis are also on the market.

A second paper, also in the journal, found a "worrisome" increase in ovarian cancers and death from ovarian cancer in women taking estrogen and progestin. However, the 58 percent increase compared with women not taking hormones wasn't statistically significant, suggesting it could have been due to chance or other factors the researchers couldn't account for. While the percentage difference in risk of ovarian cancer seems quite high, the absolute difference in cases of the disease was small, says study author Garnet Anderson, a women's health expert at the Fred Hutchinson Cancer Research Center in Seattle. It works out to 44 cases per 100,000 women in the HRT group versus 27 per 100,000 among those taking dummy pills. "This effect is a modest increase, if it's real," Anderson says. Complicating matters, she says, is that about a quarter of the women in group not receiving hormones had taken them in the past -- meaning that it's difficult to calculate a true background rate of ovarian cancer. Some doctors believe HRT still has a role as a way for women to relieve symptoms of menopause, such as vaginal dryness and hot flashes. Taken this way, the therapy could be temporary. Anderson agrees women with severe menopause problems shouldn't be dissuaded from considering HRT, even with her group's latest findings.

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New Imaging Technique Spots Hidden Breast Tumors-(HealthDayNews-01/10/2003)

Finding breast tumors at their earliest, most easily treated stage is one step closer to reality, thanks to new research conducted at the University of Colorado Health Sciences Center. In a study in the October issue of Radiology, the researchers show how adding a contrast dye to digital mammography can reveal tumors not otherwise visible with conventional screening, particularly in certain high-risk women. "We expect [this method] will become an alternative to breast magnetic resonance imaging (MRI) in evaluating difficult-to-interpret mammograms or for screening women who have an elevated risk for breast cancer," reports study author Dr. John Lewin. He is an associate professor of radiology at the health sciences center and director of breast imaging research and co-director of breast imaging at the University of Colorado Hospital Breast Center in Aurora.

The new technique may also be useful for identifying potentially malignant breast abnormalities in women who have already been diagnosed with one breast cancer, Lewin says in a statement. Current studies show conventional mammography, which uses X-ray film to image the breast, miss up to 20 percent of all breast cancers, including nine percent where a lump in the breast can be felt. The new technique -- called dual-energy contrast-enhanced digital subtraction mammography -- is filmless. Instead, it uses two ultra sharp computerized or "digital" images of the breast. One image is taken much like a regular mammogram, but displayed as a digital picture on a computer screen. The second image is taken in conjunction with a contrast dye that tries to "light up" areas of new blood vessel growth commonly associated with tumor development. The two images are laid on top of one another and the matching areas of both are subtracted or removed. What's left is very often the image of a tumor -- one that might otherwise be too small or too hidden within dense breast tissue to be seen, the researchers say.

For breast imaging specialist Dr. Michael Cohen, the technique -- and the new study -- represent a step toward the future of diagnosing breast cancer, particularly in women who may be at very high risk. "This is good science. He's taking a modality and applying some things we have done in the past, he's updated them, and he's laying the groundwork for what may be an exciting diagnostic option for certain women in the future," says Cohen, director of the Memorial Sloan-Kettering Guttman Diagnostic Center in New York City. The new research is classified as a "feasibility" study, says Cohen, meaning it is a scientific look at whether future research is warranted in this area. "The paper concludes that it is warranted, and I would definitely agree with that," Cohen says.

The small but important study involved 26 women whose traditional mammograms or breast exams found lumps or other abnormalities, indicating the need for a biopsy, but without verification of a malignancy. All 26 received the new dual, contrast-enhanced digital subtraction mammogram. Of this group, 14 of the women were ultimately shown to have cancer. Eleven of those cancers appeared as "strongly enhanced" images on the new high contrast mammogram, one appeared moderately enhanced, and two more were weakly enhanced. For the 12 women who were ultimately found to be cancer-free, the new mammogram showed either weak enhancement or no enhancement at all. Ultimately, Lewin says, the contrast dye mammograms "lit up" every malignancy and let doctors see tumors that were virtually invisible on traditional mammograms. Currently, there is no commercial machine available to perform this type of mammogram, and Lewin admits in the study he has not yet determined the precise level of radiation needed to obtain the clearest pictures.

And Cohen adds that even if the system should become commercially available, it would not be necessary for all women. "However, for those who could benefit -- someone with dense breasts for example, or when we can feel a lump, but it does not appear on a traditional mammogram -- this could one day be an excellent diagnostic tool that is fast and easy and may yield important, even lifesaving answers," Cohen says. Currently, the University of Colorado Health Sciences Center, the University of California at San Francisco, and Brigham and Women's Hospital in Boston are planning a joint clinical trial to study this new form of mammography, to determine which women it might help most. The trial is set to begin in October 2004. In the meantime, high contrast magnetic resonance imaging is available, though costly, as well as digital mammography without the use of contrast dye.

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Tamoxifen Works in Obese Women, Too-(HealthDayNews-01/10/2003)

Tamoxifen, the drug that blocks estrogen, works as well in obese women with early-stage, hormone-responsive breast cancer as in leaner women. The new research, published in the Oct. 1 issue of the Journal of the National Cancer Institute, refutes earlier studies that found an increased risk of cancer recurrence and death among obese women on tamoxifen compared to women who are leaner. But the other studies compared women in all stages of breast cancer, says James J. Dignam, the lead researcher from the University of Chicago. In the new study, Dignam says, "we looked at women with early-stage breast cancer, so-called node-negative, with totally localized tumors." The tumors were the type known to respond to tamoxifen, a drug taken orally which works by binding to estrogen receptors, thus preventing estrogen from binding to them. When this happens, the cancer cells that depend on estrogen to divide stop growing and thus die.

Dignam's team evaluated 3,385 women with early-stage breast cancer who were assigned to receive either tamoxifen or placebo after having surgery for the breast cancer. They looked at the association between obesity and the risk of breast cancer recurrence in the breast affected, in cancer in the opposite breast, of new cancers, and of overall death rates. After a median follow-up of nearly 14 years, they found that obese women had no higher risk of recurrence of the original breast cancer or death attributable to the breast cancer than did leaner women. Obese women are those with a body mass index (BMI) of 30 or above. A five-foot-five woman who weighs 180 pounds has a BMI of 30. "Obese and lean women got equal benefit in the reduction of the tumor," Dignam says. "But there were some negative consequences of obesity," he adds.

Obesity was associated with an increased risk of getting cancer in the opposite breast, of getting other cancers, and of dying from other causes, they found. During the follow-up period, obese women were 1.5 times more likely to get cancer in the opposite breast than were lean women, 1.6 times more likely to get cancers at other sites and 1.3 times more likely to die from all causes than leaner women. The study, Dignam says, points to the value of weight loss among breast cancer survivors who are obese, even though their obesity doesn't seem to affect how well the tamoxifen works. "Weight reduction and maintenance could have long-term benefits for breast cancer survivors," he says.

Another expert says the study findings will motivate her to urge her obese patients with breast cancer to lose weight. "Up until now, my main emphasis [to overweight patients] has been on not gaining weight," says Dr. Patricia Ganz, director of the Division of Cancer Prevention and Control at the UCLA Jonsson Cancer Center in Los Angeles. "Now, I will encourage them to lose weight. Losing weight may be an important part of the treatment strategy." This is one of the first studies that finds what a woman weighs when she is diagnosed with breast cancer has an influence on survival and how well she does, Ganz adds. Tamoxifen (sold under the brand name Nolvadex) is typically taken daily in pill form, usually for five years, according to the American Cancer Society. Its use after surgery can reduce the chances of the breast cancer coming back, several studies have shown.

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Global Breast Cancer Prevention Trial Launched-(Reuters-30/09/2003)

Scientists launched an international trial to determine if a drug used to treat breast cancer can prevent the disease in high-risk women. Anastrozole, which is made by AstraZeneca PLC under the brand name Arimidex, has already been shown to be as good or better than the drug tamoxifen in a trial of older women with hormone-sensitive tumors. Researchers will now test it against a placebo, or dummy pill, in 10,000 older women who have twice the normal risk of breast cancer to see if it can stop the disease from developing. Professor Jack Cuzick, of the charity Cancer Research UK and the University of London, said the new trial could have a dramatic impact on the disease and could reduce the risk of hormone-sensitive breast tumors by more than 50 percent. "It is about 1-1/2 times as good as tamoxifen in terms of treatment," he told a news conference to launch the trial, which will be run from 40 centers worldwide.

In an earlier study tamoxifen, which is the standard hormone treatment for estrogen-sensitive tumors, was shown to reduce the incidence of breast cancer by a third in women at a higher risk of the disease. "It is an important strategy for controlling breast cancer," said Professor John Forbes of the University of Newcastle in Australia, who will work on the 10-year trial.

Anastrozole belongs to a class of drugs called aromatase inhibitors. They suppress the production of the female hormone oestrogen in post-menopausal women. Tamoxifen works by preventing the action of oestrogen on the cells of the breast. Breast cancer is the most common cancer in women with more than one million cases diagnosed worldwide each year. A family history of the disease, early puberty, late menopause, delaying childbirth or not having children are risk factors. Cuzick, who will lead the international research team, said anastrozole has fewer side effects than tamoxifen, which can increase the risk of endometrial cancer, blood clots and hot flushes, so more women are able to take the drug. But there was a greater risk of bone fractures with anastrozole. Women in the trial will be closely monitored and those with low bone density will be given treatments to improve it. "All drugs have side effects but anastrozole has fewer than tamoxifen and in particular it doesn't show the slightly increased risk of blood clots or womb cancer," he said.

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Breast Cancer Deaths on the Decline-(ET-03/10/2003)

Among women in the US overall deaths from breast cancer continue to drop, according to a new report from the American Cancer Society. This improvement in survival is attributed to progress in both early detection and better treatments for the disease. But the survival gap between white and African-American women is widening. African-American women are 30% more likely to die of breast cancer than white women, according to Breast Cancer Facts & Figures 2003-2004. The latest figures show more than 90% of breast cancers are now diagnosed at a local or regional stage, when 5-year survival rates are 97% and 79%, respectively. However, since 1980, when breast cancer death rates were about equal between black and white women, black women have become increasingly more likely to die of breast cancer.

In addition, African-American women have:

ˇSlightly higher incidence of breast cancer among young women (under age 40) compared to white women (although incidence is very low in this age group among all ethnicities)
ˇ Higher incidence of large (+5cm) tumors and disease that has spread
ˇ Lower 5-year survival rate for disease that has spread (15 percent versus 25 percent for white women)

"The reasons for this disparity are not fully understood," said Michael J. Thun, MD, vice president, epidemiology and surveillance research for the American Cancer Society. "However, we do know that the widening disparity in death rates in large part reflects socio-economic factors. That is to say, more affluent women have greater access to high-quality early detection, particularly mammography, and appropriate treatment. Their breast cancers, therefore, are diagnosed at an earlier stage and treated more aggressively."

Other highlights from Breast Cancer Facts & Figures 2003-2004 include:

ˇ Breast cancer is the most frequently diagnosed cancer in U.S. women, with 211,300 invasive cases expected in 2003. It accounts for nearly one out of three cancers diagnosed in U.S. women.
ˇ Breast cancer is the second leading cause of cancer death in U.S. women; 39,800 deaths are expected in 2003, with an additional 1,300 deaths among U.S. men.
ˇ Other racial and ethnic groups have lower incidence rates than whites and African Americans.

The publication also presents breast cancer information for each state and the latest knowledge what influences survival, risk factors for the disease, including several factors that women have control over, and sections on prevention, early detection, and current breast cancer research.

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A Brisk Walk to Cut Breast Cancer Risk-(ET-29/09/2003)

A new study suggests it's never too late to start an exercise program to help prevent breast cancer. Researchers at the Fred Hutchinson Cancer Research Center and several other institutions found that postmenopausal women who exercised regularly reduced their risk of breast cancer by about 20%. Unlike some other studies, though, this one found that moderate exercise like walking was enough to provide a benefit. Previous research has suggested women need to engage in vigorous physical activity like jogging, tennis, or aerobics to reduce their risk of breast cancer. "We thought it was important to determine if moderate-intensity physical activities, such as walking, biking outdoors or easy swimming, when initiated later in life, can reduce the risk of breast cancer, since these types of activities are achievable for most women," said lead researcher Anne McTiernan, MD, PhD. McTiernan is a member of Fred Hutchinson's Public Health Sciences Division, and director of the organization's Prevention Center. Her findings were published in the Journal of the American Medical Association (Vol. 290, No. 10: 1331-1336). The study is in line with the American Cancer Society's guidelines for physical activity, said ACS deputy chief medical officer Len Lichtenfeld, MD. ACS recommends at least 30 minutes of moderate activity at least five days a week, though more strenuous exercise may be even better for lowering the risk of breast cancer.

McTiernan and colleagues based their conclusion on an examination of more than 74,000 women aged 50-79 who were participating in the Women's Health Initiative Observational Study, a long-term study of disease risk factors in American women. They asked the women about their current exercise habits, and about their exercise levels at ages 18, 35, and 50. Women whose current physical activity was equivalent to a couple of hours of brisk walking every week had an 18% lower risk of breast cancer than sedentary women. Women who got more than 10 hours of this type of exercise each week lowered their risk by about 22%. Although a greater amount of vigorous activity also reduced breast cancer risk, the amount of the reduction was not statistically significant. In an editorial accompanying the study, I-Min Lee, MBBS, ScD, said that the numbers may have not have been significant only because too few women in the study group engaged in strenuous activity, making it difficult to spot a statistical trend.

The greatest benefits from exercise were seen in lean women. Women whose body mass index (BMI) was less than 24.13 (normal weight is a BMI between 18.5 and 24.9; more than 25 is overweight, and more than 30 is obese) saw a 30% reduction in their breast cancer risk with a couple of hours of brisk walking each week. Women who were significantly overweight or obese (BMI over 28.44) did not lower their breast cancer risk by exercising. But that doesn't mean heavy women shouldn't exercise, McTiernan said. "There are many (reasons) for women of any weight to start exercising, like reducing their risk of heart disease and diabetes. But in terms of breast cancer risk, obese women will see most benefit once they start getting their weight down." That's because excess weight is thought to increase levels of hormones and growth factors (like estrogen and insulin) that may promote cancer development. "So even if a woman is exercising, if she's overeating and her body fat stays high, she's not going to get the same cancer-fighting protection as a woman with less body fat," McTiernan explained.

A second study published in the same issue of JAMA suggests that moderate physical activity -- 30 minutes, five days a week -- is enough to help women lose weight, as long as they watch what they eat, too. But once again, more may be better. The researchers, from the University of Pittsburgh, found that women who got even more exercise (40 minutes or more, five days a week) lost more weight than their moderately-active counterparts.

In McTiernan's study, the protective effect of exercise was seen even in women who were considered to be at higher risk of getting the disease, such as women with a family history of breast cancer, or who take combination estrogen-progesterone hormone therapy. Her findings indicate that even moderate activity begun later in life can have an effect, "suggesting that physical inactivity may be a modifiable breast cancer risk factor in older women," she said. Younger women also benefit from physical activity, though. Women who reported getting strenuous exercise at least three times per week at age 35 had a 14% lower risk of breast cancer compared to women who did not exercise vigorously at that age. Women who worked out vigorously at age 50 also had a slight risk reduction, but it was not statistically significant. All this points to a need for women to get up and moving, McTiernan said. Walking is one of the easiest activities to incorporate into a busy lifestyle because it doesn't require special training or equipment, she noted. "The main thing is for women to just get out there and do it, and make it something they enjoy."

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Diet, Exercise Advice for Cancer Survivors-(Reuters Health-01/10/2003)

The American Cancer Society has issued a "Guide for Informed Choices," designed to advise cancer survivors, their families, and their physicians about appropriate nutrition and physical activity during and after treatment. Dr. Jean K. Brown, of The State University of New York in Buffalo, and colleagues point out in the Guide that nearly two-thirds of Americans with cancer survive for more than five years after diagnosis. Appropriate weight, a healthful diet, and a physically active lifestyle are particularly important because survivors' risk for new cancers or other chronic illnesses are higher than normal. Published in CA: A Cancer Journal for Clinicians, the recommendations are based on new research findings since recommendations were first published in 2001.

One of the main differences in these new recommendations is that "there is more evidence about overweight/obesity and its potential to affect the recurrence of cancer and death from cancer," co-author Colleen Doyle told Reuters Health. Doyle, located in Atlanta, Georgia, is the Cancer Society's director of nutrition and physical activity. There has also been more research examining physical activity during treatment, after recovery, and in patients with advanced cancer, she added. Included with the recommendations are "Patient Pages," which answer many of the questions cancer survivors commonly have.

For example, strategies for dealing with loss of appetite and fatigue are discussed. The authors also address measures for dealing with lymphedema, the swelling in the arm or leg that sometimes occurs after cancer surgery or radiation. Physical activity is now recommended for most cancer patients. However, ability to exercise can be compromised by severe anemia or other problems, and specific precautions are advised when these factors are involved. The recommendations also include data regarding special dietary regimens and supplements. Balanced multivitamin-mineral supplements with up to 100% of "Daily Value" may be helpful. However, high doses should be avoided because of their potential to interfere with chemotherapy and radiation or to increase the risk of new cancer. "If patients are considering some type of alternative or complementary therapy, they absolutely should talk to their healthcare provider first," Doyle advises. Some can be outright harmful. And even when risk seems to be minimal, there is little or no evidence yet that such therapies are of any benefit to cancer survivors, she said.

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Treatment Options Better for Women Who Had Regular Mammograms-(ET-01/10/2003)

Many studies have shown that women who get yearly mammograms are more likely to find breast tumors while they're small and treatments are highly successful. New research confirms those findings and also shows that women who have yearly mammograms are more likely to be eligible for a lumpectomy - the breast-conserving surgery that removes the cancer, but not the entire breast. Study details were published in the journal Cancer (Vol. 98, No. 5: 918-925). "Most studies have assumed that would be the case," said lead researcher Gary Freedman, MD, of the Fox Chase Cancer Center in Philadelphia. "Ours was one of the few that was able to show that."

Freedman and his colleagues studied nearly 1,600 women age 40 and older who had been recently diagnosed with breast cancer. They divided the women into groups based on how frequently they got mammograms: 192 women had not gotten mammograms prior to being diagnosed with breast cancer; 695 women had gotten mammograms less than once a year; and 704 women had gotten mammograms at least once a year. Then the researchers compared details of the women's tumors and treatment options. All the women were evaluated by a multidisciplinary team at Fox Chase.

Among the women who were screened yearly, more than 81% were diagnosed with early stage breast cancer -- either ductal carcinoma in situ (DCIS), or a Stage I tumor. About 71% of women who had less frequent mammograms were diagnosed with early-stage disease, while just 48% of women who did not get screened had early breast cancer. Similar trends were also seen when the researchers looked only at women in their 40s. About 80% of those who were screened yearly were diagnosed with early stage breast cancer, compared to 68% of women who were screened less often, and 60% of women who did not get screened.

Mammogram history was also related to tumor size. 23% of women who were screened annually had tumors smaller than 1 cm, while just 8% of women who did not get mammograms had tumors that size. Among women in their 40s, the comparable figures were 18% and 7%. The American Cancer Society and many other organizations recommend annual mammograms for all women 40 and older, whereas some organizations recommend screening every 1-2 years beginning in the 40s. This study provides more evidence that starting mammograms at 40 is a good idea, Freedman said.

When the researchers looked at treatment options, they found that about 60% of women who got mammograms (either yearly or less frequently) were eligible for breast-conserving surgery. Among the women who were not screened, only about 40% were eligible for this less radical treatment. Treatment recommendations were not significantly different among women in their 40s. The researchers could not determine if this was because there were too few differences between the women in each screening group, or because there were too few women in this age group to draw a conclusion. Nevertheless, having more treatment options is a significant benefit for women. Women with DCIS and tumors smaller than 1 cm may not need chemotherapy after their surgery and radiation, Freedman noted. And women who have lumpectomies may adjust more quickly to a changed body image than women who have mastectomies, he said. That adjustment can be important for relationships and a good quality of life overall. "A lot of studies show women would choose lumpectomy over mastectomy if given the choice," he said.

Although the study did not investigate what happened to the women after treatment, women who have early stage breast disease and smaller tumors tend to have a better long-term prognosis than women with more advanced disease. That suggests that the women who had annual mammograms probably did better in the long run than women in the other two screening groups, he said. However, long-term follow-up of the women would be necessary to confirm that. Freedman admits his findings aren't "revolutionary," given how many studies have been conducted on mammography. "It adds additional confirmation that the older studies are still valid," he said. That confirmation is important, he added, because of a handful of studies in the past few years questioning the benefits of mammography. "It's further support for recommendations that support yearly mammography starting at age 40," Freedman said. "It needed to be said again. The message needed to be reiterated and confirmed again."

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Beating Back Aggressive Breast Cancer-(HealthDayNews-30/09/2003)

Disrupting two cell mechanisms in combination can suppress the growth of aggressive breast cancer in mice, scientists at Memorial Sloan-Kettering Cancer Center have found. That discovery is reported in a study in this week's issue of the Proceedings of the National Academy of Sciences. The research says that inhibiting both the proteins responsible for breast cancer growth and those responsible for the formation of new blood vessels slows the growth of aggressive tumors. The scientists also found that mice with a mutation commonly found in human breast cancers developed tumors that were able to grow despite a defect in new blood vessel formation (angiogenesis). When these mice with the mutation were also treated with a chemotherapy drug under development at Memorial Sloan-Kettering that inhibits a cell survival protein called Hsp90, the chemotherapy completely suppressed tumor growth. The findings suggest that combining agents that target the two cellular functions should be evaluated for treatment of advanced breast cancer.

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Study: Breast Cancer Drug Prolongs Life-(AP-24/09/2003)

The first comparison of two popular drugs has found that women with incurable breast cancer live a few months longer with one of them, but with more severe side effects. Experts said the findings, presented at a European cancer conference, do not necessarily mean all women with advanced breast cancer should be offered Taxotere, which had a better survival record. However, they said the insight would help patients and doctors weigh treatment options. "There's a huge amount of evidence that cancer patients have different attitudes to treatment," said Kathy Redmond, a patients' advocate based in Milan, Italy. "Different people are willing to trade off quality versus quantity of life. The most important thing is to give people the information and let people have a choice."

Women given Taxotere survived an average of 15.4 months, while those on Taxol survived an average of 12.7 months, said lead investigator Dr. Peter Ravdin, professor of medicine at the University of Texas Health Sciences Center at San Antonio. "Although that's a modest difference, for those people who lived longer it was important," Ravdin said. The study involved 449 women with advanced breast cancer which continued to spread despite chemotherapy. Half were given Taxol, or paclitaxel, and half were given Taxotere, or docetaxel. Both medications belong to a class of chemotherapy drugs called taxanes, which are widely used for several types of cancers and are administered by intravenous drip. The study was paid for by Aventis Pharmaceuticals, makers of Taxotere.

Taxol, developed in the United States from the Pacific yew tree and available since 1992, was the first drug of its type. Taxotere, a synthetic drug, was developed in Europe and made available in 1999. At least 25 percent of women diagnosed with breast cancer go on to develop metastatic disease, whereby the tumor spreads around the body. Nearly all such patients in industrialized countries will get a taxane during their treatment. The two taxane drugs work by interfering with cell division, but tests indicate not all cancer cells are equally affected by both agents. There are also differences in the way they are broken down and cleared from the body. In the study, there was no statistically meaningful difference between the drugs when it came to shrinking tumors. The average time before the breast cancer progressed was 5.7 months for the women on Taxotere, compared with 3.6 months among those on Taxol. The longer survival was noted whether the women were pre-menopausal or post-menopausal, Ravdin said.

However, women who received Taxotere reported more side effects, including loss of strength, abnormal fluid accumulation, diarrhea, vomiting, mouth ulcers, a reduction in infection-fighting white blood cells and more infections. Among women on Taxotere, 15 percent had fever while their white blood cell counts were low, compared with 2 percent of those treated with Taxol. The side effects mostly disappear shortly after the treatment finishes. Dr. Martine Piccart, head of chemotherapy at the Jules Bordet Institute in Brussels, Belgium, said the findings were not definitive. Both drugs were used once every three weeks in the study, but doctors have since started to give weekly infusions of Taxol. Upcoming studies are expected to clarify how the two drugs compare on that basis, said Piccart, who was not involved with the research.

Dr. John Smythe, professor of medical oncology at the University of Edinburgh in Scotland, said treating a patient involves more than balancing survival and side effects. "Some patients may prefer oral drugs, which they can take at home, and some patients travel for hours each time they have to come to the hospital," he said. "A one-hour infusion, I warn my patients, means half a day at the hospital. Half a day at the hospital means you are sitting there for hours watching people with cancer, some of them less well than you."

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Breast cancer risk higher in mothers of children with cancer-(AFP-24/09/2003)

Mothers of children who develop certain types of cancer run a greater risk of developing breast cancer, according to a new study presented to the European Cancer Conference The younger the child with a solid-type cancerous tumor is, the higher the risk for the mother, notably if the child is a boy, the study showed. Dong Pang, an epidemiologist at the Royal Manchester Children's Hospital where the research was compiled, told the conference the study was thought to be the first one to demonstrate any link between breast cancer in women and solid tumors -- other than sarcoma, meaning in bones, muscles or cartilage -- in their offspring. "The increased risk of breast cancer among mothers of children with solid tumors might be due to some form of mother-fetal interaction during pregnancy, and that hormones might play a role," Pang said. "The fetus itself is actively involved in the production and regulation of estrogen, a hormone that is an established risk factor for breast cancer," he said. Pang told cancer experts attending the conference that the Manchester study of 2,604 children under 15 diagnosed with a solid malignant tumor, there were 95 mothers who developed breast cancer -- "a third higher than the expected number of 73.5."

Among mothers of cancerous children, "the risk of breast cancer is higher during the early years following the birth of the child who subsequently develops cancer." The doctors who carried out the British research found that certain gene mutations, notably of the tumor suppressor p53, can heighten the risk of breast cancer in young women as well as certain tumors in children. "We think that a combination of disruption of the normal role of p53 in cell cycle control and hormonal disruption during pregnancy contributes to the development of breast cancer in the mother and cancer in the child," Pang said. Breast cancer, which sees a million new cases around the world every year, claimed the lives of 372,969 women in 2000, according to estimates of the International Agency for Research on Cancer.

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Study Ties Stress to Breast Cancer-(HealthDayNews-24/09/2003)

Contrary to several previous studies, new research out of Sweden claims stress can increase a woman's chance of developing breast cancer. But even the study's lead author, Dr. Östen Helgesson, cautions the findings left many things unknown, including how much stress might signal danger. Helgesson, a researcher at Sahlgrenska Academy in Goteborg, Sweden, presented his findings Sept. 24 at the European Cancer Conference in Copenhagen, Denmark. One of the problems with studying stress in relation to cancer is that the effects of stress don't manifest that quickly. While there have been some studies that show stress makes a difference in the functioning of the immune system, no one knows how that connects with the development of cancer, says Frank Baker, a psychologist and vice president for behavioral research at the American Cancer Society. "There has been a belief that breast cancer is related to stress for hundreds of years, if not thousands of years," Baker says. "We have not been able to establish conclusive linkages between experiences of stress and the occurrence of breast cancer in studies that are prospective."

The current study is a prospective one, which is one of its strengths. Prospective means that researchers followed a group of healthy women going forward, as opposed to selecting a group of women with breast cancer and delving into their past experiences. Helgesson and his colleagues followed 1,462 Swedish women, aged 38 to 60, for 24 years. In 1968 and 1991, the women had physical exams, filled out questionnaires, and were asked by a physician whether they had been under stress for a month or longer. The definition of stress in this case included tension, fear, anxiety or sleep disturbances connected with conflicts in the family or at work. The women had follow-up examinations in 1974-75, 1980-81 and 1992-93, but were not asked about stress again. Complete data was available for 1,350 of the women. The stress experience related to this study was during the five-year period leading up to the 1968-69 examination.

Women who said they were experiencing stress during this period had about double the risk of developing breast cancer than women who reported that they were not stressed. The absolute numbers, however, were low: 24 of the stressed women developed breast cancer and 432 did not. Of the unstressed women, 23 developed breast cancer and 871 did not. The study authors say they adjusted for confounding factors such as alcohol consumption, smoking, body mass index, education, family history of breast cancer and more. Overall, all the women still fell in the ballpark of low risk, says Dr. Paul Tartter, a breast surgeon at St. Luke's/Roosevelt Hospital Center in New York City. "This group of women have a relatively low risk overall compared to American women," he says.

The women in the study also did not develop cancer at an earlier age than would be expected in the population at large. "The good thing is the findings are not biased at all," says Helgesson, who is with the department of primary health care at Gothenberg University in Sweden. "Most other studies have been made on women who already have a lump in their breast and they're worried about death. They don't feel good." Although parts of the methodology are strong (namely, the fact that it is a prospective study), there are also weaknesses. As the lead author himself points out, the questionnaire used, for instance, has not been validated as an accurate way of measuring stress. If more research were to be done, Helgesson says, "we would need a better stress scale. We didn't know much about this in 1968 so we produced this simple questionnaire. This is a weakness of this study." "It's not a standardized measure of stress," Baker adds. "This research would need to be replicated with better measures of stress." "It's intriguing," Tartter adds. "And it's what we all want to hear, that stress contributes to cancer, because we can control stress."

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Lack of Oxygen May Not Halt Cancer's Spread-(HealthDayNews-18/09/2003)

A sad fact of cancer is that some tumor cells spread, signaling a worse prognosis for the patient, while others don't. An enduring question in cancer research has been, "Why?" "If you look at the public health problem of cancer, it's mostly due to cancer that has spread," says Dr. Max Sung, medical director of the Ruttenberg Cancer Treatment Center at the Mount Sinai Medical Center in New York City. "If there's a mechanism by which these cancer cells that have spread can be destroyed, that would be wonderful. The next best thing is to see if we could prevent the primary tumor from spreading in the first place." An article appearing in the Sept. 18 issue of Nature looks into just this issue: why tumor cells spread and how that deadly process can be prevented.

Scientists already knew tumor cells that don't have enough oxygen, a condition known as hypoxia, have a greater tendency to spread than those with a regular supply of oxygen. Now scientists have shown that tumor cells that are deprived of oxygen also seem to have the ability to zoom in on certain organs, which explains why certain types of cancer tend to spread to certain parts of the body. Breast cancer, for instance, has a preference for bone marrow, lungs and the liver. "This adds a novel dimension to our insight. It has shown that, not only do tumor cells acquire the ability to spread, but they also acquire the ability to home in on certain organs," says Rene Bernards, author of an accompanying article in the journal and a professor of molecular carcinogenesis at The Netherlands Cancer Institute in Amsterdam.

When faced with hypoxia, tumor cells respond by increasing production of a protein called hypoxia-inducible factor (HIF), which in turn binds to and activates different genes. The von Hippel-Lindau (VHL) tumor suppressor gene produces proteins that prevent cells from becoming malignant. It is also part of the oxygen-sensing machinery of the cell that controls the levels of the HIF. "The question is 'What is the relationship of this gene to the tumor cells spreading?'" Sung says. In this study, the researchers introduced VHL into kidney cancer cells (which normally lack a copy of this gene) and then looked for changes in the activity of thousands of other genes under conditions of adequate oxygen. To their surprise, they found that VHL reduced the production of a receptor protein called CXCR4, which is known to be over-expressed in those breast cancer cells that spread to the bone. The CXCR4 acts as a sort of homing system. "Now it turns out that if tumor cells become starved of oxygen, that they begin to express CXCR4, which allows tumor cells to migrate specifically to other organs," Bernards explains.

The findings do open up the possibility of gene therapy to correct the situation sometime in the future. At the same time, the results cast doubt on the concept of angiogenesis, which posits that cutting off blood supply to a tumor will shrink or kill it. Oxygen is carried via the bloodstream. "Although the concept that oxygen deprivation promotes tumor metastasis is not altogether novel, this is still an interesting and important study," says Charles Graham, assistant professor of anatomy and cell biology at Queen's University in Ontario. "The idea of using angiogenesis inhibitors to deprive tumors of their blood [and hence oxygen] supply as a therapeutic approach has been around for quite a while. However, this and other studies. . . indicate that reducing the blood supply to a tumor may have unintended consequences, as it may promote the spread of malignant cells."

There are other unresolved issues. "A key question that follows is whether these changes have already taken place in the primary tumor, allowing it to spread to a specific secondary site, or whether primary tumor cells that are carried to secondary organs undergo these changes after they have been exposed to the new environment," Bernards writes in his commentary. The current results seem to suggest the changes leading to this deadly cascade happen early on. This supports research that Bernards and his colleagues previously conducted that was also published in Nature. "We showed that breast cancer comes in two flavors even if they are small primary tumors, either of good prognosis or bad prognosis. Even if the primary tumor is still small, it has either already decided very early in its life that it will become malignant and aggressive and metastatic or has started out on a relatively benign path," he says. "In a way, that is good news for cancer patients because you can determine up front whether a cancer is likely to metastasize to other parts of the body or not, and we can adjust the chemotherapy requirements to this insight."

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Estrogen Blamed in Weight-Linked Cancer-(Reuters-19/08/2003)

Older women who are obese have a much higher risk of breast cancer because their fat cells release too much estrogen, researchers said. The international study comparing obese women to women of normal weight confirms what doctors have long suspected -- that fat cells release the hormone into the blood, allowing it to help turn normal cells cancerous. "There was clear hypothesis that the mechanism for the effect of obesity might be high blood estrogen levels, but no one has been able to test that directly," said Dr. Tim Key of the Cancer Research U.K. Epidemiology Unit at Britain's Oxford University.

The researchers, who report their findings in the Journal of the National Cancer Institute, said they are good news -- giving women a way to reduce their risk of breast cancer. "Women's risk is affected by many fixed factors -- a family history of the disease, the number of children they have, the age they have their children, when they start their periods and when they stop," Key said. "But obesity is something that women have a level of control over. Put simply, maintaining a healthy weight avoids extra breast cancer risk for these women."

Key and colleagues in Britain, Italy, Japan and the United States studied eight different groups of women who were past menopause -- when the risk of breast cancer rises dramatically. None of the women had cancer and none were taking hormone replacement therapy when their blood samples were first taken. The researchers then watched the women for between two and 12 years to see which ones developed breast cancer. During the study, 624 women developed breast cancer. Hormones in their blood were compared with the hormones from 1,640 cancer-free women of the same age. The more the women weighed, the higher their risk of cancer. And the more the women weighed, the higher their levels of a form of estrogen called estradiol. A woman who was obese, with a body mass index of 30 or more, had an 18 percent higher chance of developing breast cancer than a woman with a BMI of 25 -- just on the border of being overweight. "If we had made a comparison at a BMI of 22, which is relatively slim, you'd have a bigger effect," Key said in a telephone interview.

Body mass index compares weight to height, giving a broad range of healthy weights. A BMI of 22 is considered optimal, while over 25 is overweight, 30 is obese, meaning the risk of diseases is greatly increased, and 40 is morbidly obese. With 40 percent of U.S. women now obese, breast cancer, already the No. 2 cancer killer of women after lung cancer, could become an even worse problem. "Obesity is a risk factor for other diseases such as heart disease and diabetes," Joanne Dorgan, an epidemiologist at Fox Chase Cancer Center in Philadelphia who worked on the study, said in a statement. Researchers have found in other studies that a low-fat diet -- especially a diet low in animal and other saturated fats -- can reduce the risk of breast cancer. A woman's lifetime risk of breast cancer is one in nine. Heart disease is an even bigger killer, killing more than 500,000 U.S. women a year. According to the World Health Organization, 1.2 million women globally will develop breast cancer. It will kill 40,000 people in the United States this year.

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New Australian research links breast cancer to a virus-(AFP-18/08/2003)

Research strongly linking a large percentage of breast cancer cases to a new virus was unveiled by Australian scientists who say it may open up the possibility of a vaccine. Researchers from Sydney's University of New South Wales and Prince of Wales Hospital found more than 40 percent of breast cancer samples had the virus, although it was found in only two percent of normal breast samples taken from cosmetic surgery. Breast cancer is the most common form of cancer among women in many countries and affects one in 11 women in Australia. But while many risk factors have been identified, no clear causes of breast cancer have been defined until now.

The research, described at the Fresh Science 2003 forum in Melbourne and in the latest edition of the Journal of Clinical Cancer Research, showed the new virus, known as HHMMTV, to be a human equivalent of the mammary tumour virus which causes more than 95 percent of breast cancer in mice. Not only does the study demonstrate a strong link between the HHMMTV virus and breast cancer, it suggests an association between the virus and more severe forms of breast cancer, researcher Caroline Ford said. "If this virus does in fact play a role it opens up the possibility of a preventative vaccine," said Ford, a PhD student at the university and winner of the Fresh Science award. She described the discovery as "exciting" but said more work had to be done to prove the link.

The virus, usually only found in the cancerous tissue and not in the normal breast tissue from women with breast cancer, may also play an important role in male breast cancer, with over 50 percent of male samples testing positive for HHMMTV. A large number of non-cancerous diseases of the breast that are thought to increase the risk for subsequent cancer have also been shown in the study to be positive for the virus. "Many people believe that breast cancer is purely a hereditary disease, yet hereditary breast cancer is estimated to account for only five percent of all cases of breast cancer," said Ford. "In other words, we have little idea what causes 19 out of 20 cases. Our preliminary research indicates that a virus may be involved. "This new research supports the link between this virus and breast cancer in Australia. If it can be shown that this virus causes cancer, the possibility of a preventative vaccine for breast cancer would be of enormous consequence." The Fresh Science forum, which is part of the government sponsored Science Week, is a national program aimed at drawing attention to the achievements of young Australian scientists.

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Immune Cells Tied to Fatigue in Cancer Survivors-(Reuters-06/08/2003)

Nearly a third of women who survive breast cancer will develop fatigue that lasts long after their disease has been cured. Now, new research suggests that certain immune cells may play a role in this fatigue. "Many cancer patients get fatigue during treatment, but we decided to focus our research on those patients whose fatigue really doesn't improve after treatment has ended," Dr. Julienne E. Bower, from the University of California at Los Angeles, told Reuters Health. "Specifically, we've been interested in the role the immune system plays."

Previously, Bower and colleagues had shown that blood levels of certain chemicals that signal inflammation are increased in breast cancer survivors with fatigue. The current findings add to this by showing that particular immune cells, called T cells, are also involved. The results, which are reported in the Journal of the National Cancer Institute, are based on a study of 20 breast cancer survivors with fatigue and 19 similar survivors without fatigue. Fatigued survivors had T cell numbers that were 31 percent higher, on average, than those of non-fatigued survivors. In contrast, the two groups did not differ in the number of other types of immune cells. Interestingly, the more T cell numbers rose, the greater the increase in levels of an inflammatory marker linked to fatigue in the authors' earlier study.

The results suggest that there is some ongoing inflammation problem that causes fatigue in these patients, Bower said. The problem, however, must be relatively mild, since these patients don't have any symptoms other than fatigue, she added. The new findings could lead to treatments, such as drugs that block inflammation chemicals, for this type of fatigue, she added. Bower said her group is currently involved in a study comparing fatigue in cancer survivors with fatigue in non-cancer patients.

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Women Turn to New Breast Cancer Treatment-(AP-25/08/2003)

Thousands of breast cancer patients are opting for a week of radiation instead of the usual six weeks, thanks to new methods that target cancer-killing beams at the tumor site instead of the whole breast. Although early research is promising, nobody has proved the faster treatment keeps women cancer-free as long as the old-fashioned kind - or identified who are the best candidates to try it. Now the National Cancer Institute is racing to start a massive study this fall to test those questions, seeking answers before patient demand for the easier therapy becomes overwhelming. "This is the golden opportunity," says Dr. Frank Vicini of William Beaumont Hospital in Royal Oak, Mich., a pioneer of the one-week approach who is helping to plan the research. "If we don't do it now, it's not going to happen."

The hurry is in hope of avoiding past mistakes when enthusiasm outpaced evidence for new treatments. For example, doctors for years urged hormone therapy after menopause, until women were studied carefully enough to tell that long-term use actually is risky. Already, the new radiation approach, called partial-breast radiation, is rapidly gaining in popularity. More than 2,200 patients have been treated by one method of partial-breast radiation alone - a machine called the MammoSite that places a radioactive seed inside the breast. Some 267 health care centers now offer MammoSite, and untold others offer other forms of partial-breast radiation. Some patients choose it for convenience, others because they live too far from a radiation facility to make getting the traditional six, sometimes seven, weeks of daily treatments doable. "If radiation resources are virtually inaccessible to you, then maybe the shortened course would be preferred," acknowledges Dr. Paul Wallner of the NCI. But, he stresses, "patients should be aware this has not withstood the test of time."

About 70 percent of the 203,000 women estimated to be diagnosed with breast cancer this year will qualify for a lumpectomy - removing just the tumor, not the whole breast. Radiation afterward is crucial to kill any stray cancer cells lurking nearby. With proper follow-up care, lumpectomies have proved as good at curing early-stage breast cancer as breast-removing mastectomies are. But because traditional whole-breast radiation takes so long, doctors say many women choose a more disfiguring mastectomy - or forego radiation, thus running a big risk of the cancer returning. Partial-breast radiation takes only about five days, packing in larger doses because a much smaller amount of tissue is being beamed. Doctors either focus standard external radiation equipment to where the tumor was excised, or they use a method called brachytherapy - inserting radioactive seeds into the tumor site through spaghetti-like tubes. Doctors can either hand-place the seeds or use MammoSite.

A handful of studies - including one published last week by Vicini - have tracked small numbers of patients for five years and suggest that both partial- and whole-breast radiation are equally effective. Those studies typically restrict partial-breast radiation to carefully selected women - those with very small tumors that, upon removal, showed wide margins of cancer-free tissue and no signs of spread. The women also tend to be in their 40s or older, although doctors disagree on age cutoffs. Vicini says about a third of lumpectomy patients meet those criteria. One big question is whether it's OK for more women to try partial-breast radiation. That's a question the NCI-funded study should help answer. It will enroll at least 6,000 women, comparing the two radiation approaches for long-term effectiveness. NCI hopes to begin the study this fall, when it will announce how to volunteer. Also, MammoSite's maker plans to track 2,500 recipients to see how they fare long-term; 450 are enrolled in this registry so far. Until the final proof is in, what should physicians tell women? "I consider it an option for women, and I tell them that because we haven't been doing brachytherapy as long as whole-breast radiation, there are still some unknowns," says Dr. Troy Scroggins of New Orleans' Ochsner Clinic Foundation, which has treated about 200 patients.

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Node Search Avoids Major Breast Cancer Surgery-(Reuters Health-06/08/2003)

A relatively simple procedure to find out if breast cancer has spread can help patients avoid a much bigger operation with debilitating complications, new research indicates. To determine the best treatment for breast cancer patients, doctors need to figure out how far it has spread. The first place this cancer usually goes is to lymph nodes in the armpit. Traditionally, surgeons would remove a big piece of tissue in the armpit in an attempt to get as many nodes as possible. While this operation, known as axillary dissection, was useful in determining if the cancer had spread, it can also be painful and cause a chronic arm-swelling problem called lymphedema.

In the last decade, a new technique, known as sentinel-node (SN) biopsy, was developed as an alternative to axillary dissection. This technique is based on the belief that when breast cancer spreads to armpit nodes it goes to one node--the sentinel node--before any others. Therefore, if the sentinel node doesn't show cancer then none of the other nodes will. With SN biopsy, the surgeon injects blue dye or radioactive material into the breast with cancer and then follows these chemicals into the patient's armpit to find the sentinel node. Unlike axillary dissection, only the sentinel node is removed. If the sentinel node shows cancer, axillary dissection is still needed to determine exactly how many nodes have cancer. In contrast, if there is no cancer in the sentinel node -- and often times there isn't -- then axillary dissection is not needed. The new findings, which are reported in The New England Journal of Medicine, show that SN biopsy is a safe and accurate way of determining if breast cancer spread to the lymph nodes in the armpit.

Dr. Umberto Veronesi, from the Istituto Europeo di Oncologia in Milan, Italy, and colleagues evaluated SN biopsy in 516 patients with breast cancers that were no greater than 2 cm in diameter. All of the women underwent SN biopsy, but in some axillary dissection was always performed, whereas in others axillary dissection was only done if the sentinel node showed cancer. The team found that SN biopsy was very accurate in predicting if cancer had spread to the other nodes. Most importantly, SN biopsy never falsely indicated that cancer was absent. This study "provides evidence justifying the use of SN biopsy as part of the assessment of the stage of breast cancer," the authors conclude. When SN biopsy indicates no cancer in the sentinel node, axillary dissection can be avoided, thereby reducing postoperative complications and hospital costs, they add.

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Breast Cancer Doesn't Preclude Pregnancy-(HealthDayNews-11/08/2003)

There's no increase in the risk of death if a woman conceives and delivers a baby after she's diagnosed with breast cancer. That's the claim of a study in the journal Cancer.

Researchers at the Fred Hutchinson Cancer Research Center compared death rates among 438 women with breast cancer who had children after their diagnosis and 2,775 women with breast cancer who didn't have children after being diagnosed with cancer. All the women were younger than age 45. The median follow-up time for the women after delivery ranged from four to nine years. Women who had children at least 10 months after their breast cancer diagnosis actually had a decreased risk of death compared to women who did not have children, the study says. Despite that, the researchers say that finding should not be seen as an indication that pregnancy offers a protective effect. The study also found an increased risk of death among subgroups of women who were pregnant when they were diagnosed with breast cancer. These subgroups included women who delivered babies within three months of their cancer diagnosis, those 35 years or older at diagnosis, and those with certain disease characteristics. The authors note their finding of a decreased risk of death in women who gave birth 10 or more months after being diagnosed with breast cancer is similar to findings of some previous studies.

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Nipple Fluid May Be Good Breast Cancer Screen-(Reuters Health-25/07/2003)

Fluid expressed from the breast carries proteins that may indicate the presence breast cancer. Moreover, the fluid can be obtained with relatively little discomfort. Dr. Richard Zangar, of the Pacific Northwest National Laboratory in Richland, Washington, and associated looked at a new method for obtaining "nipple aspirate fluid" in which the woman massages the breast, applies gentle heat, and then uses a patented breast pump. Among 121 healthy, non-lactating volunteers, more than 90% were successful in producing fluid, the team reports in the medical journal Breast Cancer Research and Treatment. As Zangar told Reuters Health, "Women find this more acceptable than ductal lavage," an irrigation procedure. When the fluid samples were collected, sensitive testing identified a total of 64 proteins. Nearly a quarter of the proteins are altered in blood or tumor specimens from women with breast cancer, previous research has shown, and so represent "biomarkers" of breast cancer. "Now we need to do a systematic comparison between healthy women and women with early stage breast cancer to identify candidate proteins in nipple aspirate," Zangar said. He expects that his group will identify patterns of proteins that point to different types of cancer, and which could thus be used both for diagnosis and to guide treatment.

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Method to Gauge Breast Cancer Risk May Be Flawed- (HealthDayNews-17/07/2003)

A research tool commonly used to determine links between diet and breast cancer could be seriously flawed. That's the conclusion of a research letter that appears in The Lancet. The method in question is known as the "food-frequency questionnaire," or FFQ. Researchers say defects in the basic methodology behind the questionnaire could mean it fails to reveal the association between dietary fat and the development of malignant breast tumors. "We believe that, in the past, finding links between breast cancer and fat intake has been hampered by imprecise research methods which appear to have obscured a link between the two," says lead researcher Dr. Sheila Bingham, deputy director of the Medical Research Council Dunn Human Nutrition Unit in Cambridge, England.

A food-frequency questionnaire requires patients to rely on their memory to answer a series of questions designed to reveal their dietary habits during a specific time period. When combined with health history and medical data, the dietary information is analyzed and used to postulate links between what people eat and their risk of disease. An alternate method of dietary calculation is the "food diary." Here, patients write down everything they eat for a specific period of time. That information is then used by researchers to calculate food-disease risk factors. The food diary is the better way to go, Bingham's research contends. "We believe that the comprehensive food diaries that our participants completed give a more accurate picture of eating habits compared to other methods," Bingham says.

Bingham's report comes on the heels of a July 17 report in the Journal of the National Cancer Institute. In that study, researchers used a series of food and lifestyle questionnaires -- not diaries -- that were completed over several years to document a positive association between high fat diets and breast cancer. However, previous studies using similar reporting systems have yielded conflicting results, causing a lot of controversy and leading some researchers to question if a link between dietary fat and breast cancer even exists. For New York University breast cancer expert Dr. Julia Smith, Bingham's research letter offers an important new slant on why past research has met with such diverse results. And, she says, it may even help to explain how the controversy concerning study results started. "We have always suspected a link between fat intake and breast cancer, but somehow the science could never fully verify that it was so," says Smith, a clinical assistant professor at the university.

The new study involved some 13,000 women. At the start of the study, they each completed a food-frequency questionnaire, and most also submitted a more precise diary that listed everything they ate for seven days. The data were collected between 1993 and 1997. By the year 2000, 168 of the women had developed breast cancer. At the time of their diagnosis, doctors analyzed the dietary data collected at the start of the study and compared it to data generated by the women in the study who remained healthy. In looking just at the food diaries, Bingham found that the women who consumed the most fat (about 90 grams a day) were more than twice as likely to develop breast cancer than those who consumed fewer fatty foods (about 40 grams a day).

The surprising twist to the research became apparent when Bingham looked at the food-frequency questionnaires also completed by the women. Based on these answers, there appeared to be no association between dietary fat and cancer, even though Bingham says the women's food diaries -- and their medical history -- told a different story. The only obvious conclusion, she says, is that the food-frequency questionnaires were simply not an accurate reflection of what the women were eating -- and more importantly, masked the obvious link between high-fat diets and breast cancer. According to the entries in the diaries, the foods most likely to increase the risk of breast cancer include saturated fats -- which are found mostly in high-fat milk, butter, and meat -- as well as biscuits, cakes and other baked goods, Bingham says.

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Hormone therapies increase breast cancer risk: new research-(ET-07/08/2003)

Hormone replacement therapies place women at increased risk of developing breast cancer, according to a study involving more than a million women and published in the British weekly medical journal The Lancet. The comprehensive study bears out previous suspicions of a link between combination (progestagen-oestrogen) hormone replacement therapies (HRTs) and the development of breast cancer. The use of HRT by British women aged between 50 and 64 has caused an estimated 20,000 extra breast cancers over the past decade, 15,000 of which are likely to be associated with combination HRT therapies, the study found. The study is also the first to report that HRT increases the risk of dying from breast cancer.

The 'Million Women Study' led by Valerie Beral from Cancer Research UK's Epidemiology Unit in Oxford, southern England, focused on the effects of specific types of HRT on breast cancer. Beral monitored 1,084,110 British women aged between 50 to 64, from 1996 to 2001, half of whom had followed HRT at some point in their lives. Of the women surveyed, 9,364 developed breast cancer after an average 2.6 years, with 637 women dying of the disease after an average of 4.1 years.

Current users of all types of HRT were at an increased risk of developing breast cancer, and faced a 22 percent increased risk of dying from the disease. Use of combination HRT caused a four-fold increase in the risk of developing the disease compared to oestrogen-only HRT, the study shows. The study found that the risk of breast cancer rose in proportion to the length of the HRT use, but that the increased risk appeared to wear off a few years after discontinuing the therapy. Commenting in The Lancet, Beral said: "Combined HRT is usually prescribed for women who still have a uterus, to avoid the increased risk of cancer of the uterus caused by oestrogen-only therapy". "Since our results show a substantially greater increase in breast cancer with combined HRT, women need to weigh the increased risk of breast cancer caused by progestogen against the lower risk of uterine cancer." "Comparing the risks is by no means simple," Beral added, "and women may well want to discuss their options with their doctor."

The implications for medical practitioners are discussed in a commentary by a Dutch scientist published alongside Beral's article. To Chris van Wheel from the University of Nijmegen, the Netherlands, the problem lies with women who are already taking HRT -- an estimated 20 to 50 percent of all Western women aged between 45 and 70. Van Wheel recommended that this group discontinue HRT use as soon as possible, although practitioners should introduce the issue in a positive, supportive way in order to avoid panic reactions. The Dutch scientist also sees "a great need for a public information campaign", with the medical profession in the lead, with current evidence of increased risks stated "in clear but unsensational wording".

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Fatty Foods Tied to Breast Cancer in Younger Women-(Reuters Health-15/07/2003)

Younger women who regularly eat foods containing certain types of fat may be increasing their chances of developing breast cancer, new research suggests. This is the first study to link fatty foods with breast cancer in women who have not yet reached menopause, lead author Dr. Eunyoung Cho, from Harvard Medical School in Boston, told Reuters Health. Previous studies, which have focused mainly on postmenopausal women, have not tied fatty foods to cancer. The current findings are based on a study of more than 90,000 premenopausal women who were followed for 8 years. When the study began in 1991 and again in 1995, the women were surveyed regarding how often they ate various fatty foods. The results are published in the Journal of the National Cancer Institute.

During the study period, 714 women developed breast cancer. According to Cho, "most of these women were still premenopausal at the time of diagnosis." The total amount of fat consumed was not linked to breast cancer, but eating certain types of fat was, Cho said. Eating animal fat, which is usually found in red meat and high-fat dairy foods, increased the risk of cancer, while eating vegetable fats did not. Women who ate high amounts of animal fat were up to 54% more likely to develop breast cancer than women who ate the lowest amounts, the findings indicate.

Exactly how fatty foods raise the risk of breast cancer is unclear, Cho said. After being eaten, fat is thought to raise body levels of certain hormones that could promote breast cancer. Still, this doesn't explain why eating animal fats, but not vegetable fats, made cancer more likely. "We suspect there is some present only in animal fats that increases the risk of breast cancer," she added. Cho noted that her team plans to follow the current group for a few more years to see if fat intake before menopause affects the risk of cancer after menopause.

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Value of Radiation Confirmed in Early Breast Cancer-(ET-23/07/2003)

A new British study confirms that women with the earliest stage of breast cancer, ductal carcinoma in situ (DCIS), have fewer recurrences if they get radiation therapy after having the cancerous tissue removed. In the United States, most women with DCIS who have a lumpectomy also get radiation. This latest study should reassure women that their radiation treatments are appropriate and effective. It could also reassure doctors, according to study co-author Joan Houghton, of the UK Coordinating Committee on Cancer Research. "These results are important because many surgeons, especially in the (United Kingdom), think that radiotherapy is not required if the disease is completely removed in surgery," she said in a statement. DCIS is cancer that is confined to the milk ducts and has not spread into the surrounding breast tissue -- although there is a chance it could spread. More cases of DCIS are being detected in the United States thanks to wider use of screening mammography, which can identify this cancer before it becomes large enough to be felt.

Writing in The Lancet (Vol. 362, No. 9378: 95-102), Houghton and colleagues report the results of a study of about 1,700 women who had lumpectomy for DCIS. Some of the women received no additional treatment after having the cancer removed from their breast, while others got either radiation therapy or tamoxifen, or a combination of the two. The researchers found that women who got radiation therapy lowered their risk of getting DCIS again in the same breast by more than 60% compared to women who did not receive radiation. The risk of getting invasive cancer in the same breast decreased by more than 50% in women who got radiation compared to those who did not. That translates to one invasive tumor prevented for every 36 women who get a five-week course of radiation, the researchers said. Radiation did not reduce the risk of getting cancer in the other breast.

This study supports the results of two other large trials that found similar reductions in risk with radiation. However, the researchers say some questions still remain about which women may be best suited to radiation treatment. They say longer follow-up is needed to determine whether all DCIS patients should get radiation, or whether women at low risk of recurrence can go without. More research is also needed to determine how tamoxifen may impact disease recurrence in women with DCIS, according to the study authors. In this study, tamoxifen appeared to have little impact on recurrence, regardless of whether the women taking it had gotten radiation or not. The authors say long-term follow-up may clarify how beneficial tamoxifen actually is. They also recommend studies of newer drugs, such as aromatase inhibitors, which have been shown in previous research to be as effective as tamoxifen and possibly even better.

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Gene Identified May Explain Racial Differences in Outcomes of Breast Cancer-(ET-15/07/2003)

According to a recent article published in Breast Cancer Research, researchers have identified a gene that may explain the differences in survival between black women and white women who are treated for breast cancer. Breast cancer is diagnosed in over 200,000 women and claims the lives of approximately 40,000 women annually in the United States alone. Researchers are trying to determine specific genetic or biological characteristics that may be associated with the development of breast cancer in order to identify women at a high risk of developing the disease and/or to identify specific targets for novel therapeutic approaches.

Data has shown that survival outcomes have remained worse for black women treated for breast cancer compared to white women. Researchers have attempted to explain this disparity through the compilation and evaluation of data; however, no differing variables had been discovered to clarify this survival difference. Researchers from the George Washington University Medical Center recently discovered a gene that may be, at least in part, responsible for the different survival outcomes between black and white women diagnosed with breast cancer.

These researchers examined samples of breast cancer tissue and normal breast tissue. Of these samples, the gene known as BP1 was expressed in 80% of cancerous tissues, while only 15% of normal tissue specimens expressed low levels of the gene. Furthermore, 89% of black women had cancer that expressed BP1, compared to only 56% of white women. BP1 expression was significantly associated with estrogen-receptor negative (ER-negative) breast cancer and did not display a correlation between cancer size, aggressiveness of spread to lymph nodes. The researchers conclude that BP1 may be a potential target for treatment and early detection of breast cancer. In addition, BP1 may be responsible for the differences in survival between black and white women with breast cancer. Further studies are warranted to confirm these findings.

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High-Dose Chemo for Breast Cancer a Mixed Bag-(HealthDayNews-02/07/2003)

Two new studies seem to have reached vastly different conclusions on how to best treat aggressive, recurring breast cancer. The first report, out of Northwestern University's Feinberg School of Medicine in Chicago, concludes that adding high-dose chemotherapy with bone-marrow transplantation to traditional chemotherapy offers little benefit to women suffering from breast cancer. Not only that, but several women on the high-dose regimen died of leukemia or other disorders. The second study, out of the Netherlands, found exactly the opposite: high-dose chemotherapy and bone-marrow transplantation did improve relapse-free survival for certain patients. Both findings appear in the July 3 issue of the New England Journal of Medicine. A debate has long simmered over whether high-dose chemotherapy might improve the odds for women with aggressive, recurring breast cancer. Because the high-dose treatment destroys marrow, the procedure is accompanied by bone-marrow transplantation. Both studies looked at women who had positive lymph nodes and who had undergone surgery to remove the primary tumor.

The Northwestern researchers randomly assigned 540 women to receive either six cycles of standard chemotherapy or standard chemotherapy followed by high-dose chemotherapy with bone-marrow transplantation. The women were enrolled between 1991 and 1998 and were followed for a median of just over six years. After assessing 511 women, the authors found the six-year overall survival rate was 62 percent in the group that received standard chemotherapy alone and 58 percent in the group that received high-dose chemotherapy, a difference not considered statistically significant. Also at six years, 48 percent of the patients in the standard group were free of recurrence versus 55 percent in the high-dose group -- again, not a significant difference. But, 18 of the women getting the high-dose chemotherapy died.

The Dutch study looked at 885 women. All patients had five courses of a standard chemotherapy, followed by radiotherapy and tamoxifen, while one group also received high-dose chemotherapy with bone-marrow transplantation. The five-year, relapse-free survival rates were 59 percent in the conventional group and 65 percent in the high-dose group. Among women with at least 10 positive lymph nodes, the recurrence-free survival rates were 51 percent in the conventional group and 61 percent in the high-dose group.

Just as the studies reach different conclusions, experts too are divided on their significance. "When I look at the overall evidence [from these and other studies], I don't think high-dose chemotherapy is an accepted standard regimen," says Dr. Jeffrey Abrams, associate chief of the clinical investigations branch at the National Cancer Institute. "It may still be an area of investigation" for the future, he adds, "but with that said, I don't think it should be part of standard treatment."

However, Dr. George Somlo, associate director of high-dose chemotherapy in the division of medical oncology and therapeutics research at City of Hope National Medical Center, understandably has a different perspective. "The study from the Netherlands is the one I would consider more meaningful," he says. "The Dutch study to me is a better study in terms of design and credibility. Clearly they found that in those with 10 or more lymph nodes -- high-risk characteristics -- there was a definite advantage, in my mind."

"Both studies show no difference in overall survival between those that got high dose and those got conventional chemotherapy, so the only thing they show is that there may be a decrease in relapse rates in those who got the high dose," says Dr. Avi Barbasch, an associate clinical professor of medical oncology at the Mount Sinai School of Medicine in New York City. "It took a little bit longer for the disease to come back."

Another question is whether high-dose chemotherapy with bone-marrow transplantation has been supplanted by other therapies in the years since these studies were begun. "For people who have 10 or more nodes, I think the treatment today would be quite different," Barbasch says. Growth factors stimulate the body to make white blood cells. "One of the things that's getting a lot more play is doing it more frequently, dosing weekly or every two weeks with growth-factor support in between so the patient can withstand more intensive treatment," he adds. "People were hoping that given how toxic the [high-dose chemotherapy] treatment was that we would see a rather major effect, and the effect that we're seeing is not different than the types of improvements that we've seen by the simple addition of a new drug like Taxol to standard regimens, or a recent study that gave the standard treatment every two weeks instead of every three weeks," Abrams says. "Improvements are in the range of 5 to 10 percent, but those kinds of improvements haven't necessitated these high doses, which are extremely expensive and have severe side effects."

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Five Years of Tamoxifen Best for Most Women-(ET-26/06/2003)

A new study confirms that taking tamoxifen for five years better protects most breast cancer patients from a recurrence of the disease than a shorter regimen. Although the drug has been used for 25 years to treat women with breast cancer, there has been some dispute over just how long to continue treatment. Researchers in Italy compared a two-year regimen with a five-year regimen in women with early-stage breast cancer. They reported their results in the Journal of Clinical Oncology (Vol. 21, No. 12: 2276-2281). The researchers studied 1,901 women between the ages of 50 and 70 who had undergone surgery for early stage invasive breast cancer (some had also had radiation therapy). All began taking tamoxifen soon after their initial treatment to try to prevent recurrence. After two years, about half the women stopped taking tamoxifen; the rest continued taking the drug for three more years, for a total of five years.

The researchers followed the women for more than four years after the first group stopped tamoxifen treatment. Overall, they found little difference between the two groups when they looked at how many women had died and how many women had a recurrence of their disease. But when they examined only women with estrogen-receptor positive tumors, they found a significant difference. More than 28% of these women who took tamoxifen for just two years had a recurrence of their cancer (166 women), compared to 23.5% among the five-year tamoxifen group (131 women).

Tamoxifen works by blocking the effect of estrogen, which promotes the growth of ER-positive tumors. Women in the five-year group experienced more blood clots than women in the two-year group, but the researchers determined that the cancer protection they received from the tamoxifen outweighed this risk. The researchers say one way to address the problem of blood clots is to give women at high risk for clots newer drugs like anastrozole, which are effective but have lower incidence of this side effect. The debate over how long to continue tamoxifen use has centered on the fact that it has potentially harmful side effects. Previous research has shown it can increase the risk of blood clots in the legs and lungs, as well as cancers of the uterus. Because of this, doctors have looked to see if they could lower this risk while maintaining the same level of protection against breast cancer recurrence.

"Previous studies have shown the five-year mark to be about optimal, and this study confirms it," says Rick Alteri, MD, a medical editor for the American Cancer Society. The fact that the results were better in women with estrogen-receptor positive tumors was not a surprise, he adds, and is in line with current practice in the United States. "Most doctors have breast cancer specimens tested for estrogen receptor status, and only prescribe tamoxifen if it is positive. This study also validates the wisdom of this approach."

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Hormone Pills May Spur Breast Cancer-(AP-25/06/2003)

More negative fallout from a landmark government study suggests breast cancer linked to estrogen-progestin pills may be fast-growing and hard to detect, clarifying risks for millions of women still using hormone treatment. "Hopefully, it will convince women to reconsider," said Dr. Susan Hendrix of Wayne State University in Detroit, a co-author of the new analysis. "We've got to find a better way to help women with their menopausal symptoms." Some previous studies suggested breast tumors might be less aggressive in hormone users; other studies indicated the opposite. Previous research also suggested that hormones might make breast tissue more dense, hindering the detection of tumors.

Seeking more definitive answers, the researchers took a closer look at data from the government's landmark Women's Health Initiative study, which was halted last summer after it was found that estrogen-progestin pills raise the risk of heart attack, strokes and breast cancer. While last summer's findings led many women to stop taking hormones, Hendrix said an estimated 3 million women still use them, primarily to relieve hot flashes and other symptoms of menopause. The latest findings appear in the Journal of the American Medical Association. The analysis involved 16,608 women ages 50 to 79 who used either combined hormone treatment or dummy pills for an average of five years. As of January, breast cancer had developed in 245 women who used the combined hormone treatment and in 185 women who had taken dummy pills. Hormone users' tumors were larger at diagnosis, 1.7 centimeters on average versus 1.5 centimeters in placebo women. Tumors had begun to spread in 25.4 percent of hormone users, compared with 16 percent of placebo women.

The researchers said this appears to mean that in women on estrogen-progestin, the tumors both grow faster - that is, they are more aggressive - and escape detection longer. Overall, women on both hormones faced a 24 percent increased risk of breast cancer - equal to eight extra cases of cancer per year for every 10,000 women taking the pills. The increased risk did not appear in the first two years of treatment. But Hendrix said the tumors may have been present early on but were not detected until later because of hormone-induced breast density. The new analysis did not examine breast density. But researchers think progestin may be the culprit because it can cause breast cells - both normal and abnormal - to proliferate, an effect that may be accentuated when the hormone is combined with estrogen.

Wyeth Pharmaceuticals, maker of the Prempro pills used in the study, said hormones remain an appropriate therapy when used at the lowest possible dose for the shortest possible time. The latest analysis is by far the most conclusive, said Dr. Peter Gann, an associate professor of preventive medicine at Northwestern University who was not involved in the study. It "further worsens the news for long-term hormone replacement therapy. It suggests the excess breast cancer risk is not trivial," Gann said. Last summer's Women's Health Initiative findings shattered long-held beliefs that hormones are good for women's hearts. Last month, another analysis of data from the study found that instead of sharpening the mind, hormones may double the risk of Alzheimer's and other forms of dementia.

A second, smaller study in the journal also confirmed a link between combined hormone treatments and breast cancer and suggested estrogen-only treatment may be safer. The study involved 975 Seattle-area women ages 65 to 79. The greatest breast cancer risk was in women who used estrogen-progestin for at least five years, even if they took the progestin component only some days a month. Those who used estrogen alone, even for 25 years or longer, showed no appreciable increased risk, according to the study, led by Dr. Christopher Li of Fred Hutchinson Cancer Research Center in Seattle. Estrogen alone is recommended only for women with hysterectomies because it can cause uterine cancer unless balanced by progestin. The researchers said more definitive answers will come from the continuing estrogen-only part of the Women's Health Initiative study.

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Diabetes Tied to Increased Risk of Breast Cancer-(Reuters Health-27/06/2003)

Women with diabetes may have a slightly elevated risk of developing breast cancer, new study findings suggest. "We found there is a small but statistically significant association," said study author Dr. Karin B. Michels, an associate professor of epidemiology at Harvard Medical School in Boston. The results, drawn from the ongoing Nurses' Health Study, showed that women with type 2 diabetes were 17 percent more likely to develop breast cancer than those without diabetes. Type 2 diabetes, the most common form of the disease, usually develops in adulthood though it is on the rise in children, who are increasingly becoming overweight. In their analysis, Michels and colleagues accounted for various factors that may have influenced the results, such as heavy alcohol consumption, obesity and a family history of breast cancer.

The research involved 116,488 female nurses who were ages 30 to 55 when the study began in 1976. They were followed for the next two decades, during which time there were 6,120 cases of type 2 diabetes and 5,605 cases of breast cancer. Of those who developed breast cancer, 202 had diabetes. The link between diabetes and breast cancer was apparent in postmenopausal but not premenopausal women, according to findings reported in the June issue of the journal Diabetes Care. Michels said the explanation for the association between the two diseases is not clear. "How all of this works mechanistically we're not entirely sure," she told Reuters Health. Some investigators have speculated that elevated levels of insulin in the blood of diabetics may somehow promote breast cancer, the study authors note in the report.

Insulin is a hormone produced by the pancreas that allows glucose, or blood sugar, to enter cells to be converted into energy. This process is impaired during insulin resistance, when the body becomes less sensitive to the effects of insulin, prompting the pancreas to pump out more insulin to try to compensate. Efforts to prevent diabetes by encouraging people to exercise regularly, control their weight and eat a healthful diet may have a new, added benefit for women, according to Michels. "Maybe we can prevent some breast cancers as well," she said.

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Breast cancer risk nearly halved by frequent miso soup intake-(ET-18/06/2003)

The risk of developing breast cancer was nearly halved among Japanese women who had miso soup at least three times a day compared with those who had one or less bowl of the traditional soya-based dish per day. A team of Japanese researchers concluded that "frequent miso soup and isoflavone consumption was associated with a reduced risk of breast cancer," in the study published in the US-based Journal of the National Cancer Institute.

Miso is pureed steamed soybeans, mixed with salt and other fermenting agents. The research team, headed by Shoichiro Tsugane of Japan's National Cancer Center, tracked 21,852 Japanese women, aged 40 to 59 years old, across Japan over 10 years from 1990 and studied their consumption of soyabean products, such as miso soup and tofu. On average, 0.098 percent of those who had one or less bowl of miso soup developed breast cancer every year, while the incidence was reduced to 0.057 percent among those who had at least three bowls per day, the study found. "Consumption of miso soup and isoflavones ... was inversely associated with the risk of breast cancer," said Seiichiro Yamamoto, a researcher at the Japanese institute and leading author of the study.

Laboratory studies have already shown that isoflavones, a group of compounds that the soyabean contains in abundance, inhibit breast cancer. Until now, however, various epidemiological studies had shown inconsistent associations between the breast cancer risk and consumption of soyabean and isoflavones, Yamamoto said. The study could not show statistically significant evidence that other soyabean products are associated with reduced breast cancer risk, Yamamoto said. "The tendency for lowered breast cancer risk (associated with other soyabean products) was observed but we need to do further studies to confirm it," he said. Researchers also believe frequent miso soup consumption may reduce the risk of prostate cancer (news - web sites) among men, Yamamoto said. But Yamamoto cautioned that miso is no miracle food, as it contains a lot of salt, which can cause stomach cancer and high blood pressure, among other diseases. He added, though, a balanced diet containing a lot of soyabeans "is healthy overall" and was believed to reduce the risk of developing cancer. "Very generally speaking there is a perception that the traditional Japanese diet is healthy. We will study what part of it had what kind of effect on people. Some were good, some were bad," Yamamoto said.

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Selenium May Guard Against Breast Cancer-(HealthDayNews-17/06/2003)

Selenium may help guard against breast cancer in people who are genetically predisposed to the disease. That's what University of Illinois at Chicago researchers report in the June 15 issue of Cancer Research. Selenium is a trace element found in foods such as liver, kidneys and certain kinds of nuts. "For over 20 years, animal studies have shown that tiny amounts of selenium in the diet can suppress cancer in several types of organs. The animal data is very strong, but human data is just emerging," study co-author Alan Diamond, professor and head of human nutrition, says in a news release.

It's unclear just how selenium might help prevent cancer. "We believe there are certain proteins in mammalian cells that contain selenium that can mediate the protective effects, but proving that is difficult," Diamond says. In this study, he and fellow researcher Jun Hu examined the role played in breast cancer by a selenium-containing protein called glutathione peroxidase, which is selenium-dependent and acts as an antioxidant. They did this by looking at a particular selenium-containing gene that encodes for selenium-containing proteins. Using tissue samples, they compared the genes from 517 people who were cancer-free with the genes of 79 breast cancer patients. They found there's a difference in the frequency of different versions of the genes of the cancer patients, compared with those without cancer. They also found those differences have a functional consequence. That suggests a person with a certain version of the gene may require more selenium in their diet to get the cancer-prevention benefits. By identifying what version of the gene a person has, doctors may someday be able to prescribe an appropriate amount of selenium to provide protection against cancer.

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Vitamin D May Aid Breast Cancer Treatment-(HealthScoutNews-06/06/2003)

Vitamin D could hold a clue to more effective breast cancer treatment. That's the suggestion put forward by a group of Dartmouth researchers in a report in the June issue of the Journal of Clinical Cancer Research. The study, which involved the treatment of breast cancer tumors in mice, adds to a growing body of evidence that a derivative of vitamin D known as EB1089 may yield some powerful anti-cancer properties, particularly when combined with radiation therapy. "When compared to other cancer treatments, the vitamin D analog is much less toxic and, at least preliminarily, it appears to aid radiation therapy in impacting the growth of tumor cells," says lead author Sujatha Sundaram, a research assistant professor at Dartmouth Medical School.

An analog is a synthetic, laboratory-made derivative of a parent compound -- in this case vitamin D -- that is genetically engineered by adding or removing certain chemical elements. In the instance of EB1089, it was necessary to modify vitamin D because "at the dose you need to give to have an effect on cancer, it could cause some side effects," Sundaram says. Those side effects would include an overload of calcium, a condition known as hypercalcaemia. The analog used in the study, Sundaram says, has little or no toxic reaction, even in high doses. Adding the vitamin D to the treatment regimen is thought to enhance the ability of the radiation to bring about apoptosis -- or cell death. It also reduces the proliferation, or growth of cancer cells, in the tumor itself, Sundaram explains. "These are all things that radiation therapy can accomplish on its own. But the EB1089 appears to make the treatment more effective, possibly reaching pockets of cells that might otherwise be missed, or in encouraging apoptosis in cells that for one reason or another might be stubborn or resistant to the effects of the radiation," Sundaram says.

While the finding in this particular study is unique, previous research on vitamin D found it was effective against both prostate and breast tumors. Currently, a large European trial is testing EB1089 on human cancer patients. For radiation oncologist Dr. Victor Ayzenberg, the study results and the compound offer hope. "It's a very good study, with important information. It would be great if we can use it with patients," says Ayzenberg, a clinical professor of medicine at the Mount Sinai School of Medicine in New York City. It's a simple idea, he adds, but it clearly has merit.

The new study was small, involving just eight mice, each implanted with human breast cancer cells. When tumors reached approximately 200 millimeters in size, half the mice received an infusion pump with a continuous flow of EB1089 for eight days. The other mice received a pump containing a harmless solvent solution.After a few days rest, both groups of mice received three "fractions" -- or doses -- of radiation therapy over the course of three days. The tumors were then monitored for 25 to 30 days, checking for both size and spread. The result: The mice treated with EB1089 had a far faster rate of tumor regression, with tumors shrinking to a much smaller size. In the final analysis, the tumors in the mice receiving EB1089 plus radiation were approximately 50 percent smaller than those receiving radiation alone. In addition, Sundaram says, there was less cancer cell proliferation -- or cell growth -- in the mice treated with the vitamin D analog. This, she says, indicates that EB1089 not only helped encourage apoptosis of the tumor cells, it also blocked new tumor cell growth. As encouraging as the findings are, Sundaram stresses cancer patients should not assume that vitamin D supplements will have the same effect. And she warns that overloading on supplements could be dangerous.

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Detecting Breast Cancer: An Image Problem-(HealthDayNews-16/06/2003)

In the high-stakes world of breast cancer, the traditional mammogram often finds itself pitted against the newer, more technologically savvy magnetic resonance imaging (MRI) as the best way to identify malignant tumors. Now, a study in the June 15 issue of Cancer shows a woman's risk of the disease could be an important factor in determining whether she benefits from an MRI. "Our research shows that the benefits of MR screening in low-risk women are small, while the disadvantages of such a screening in this group are high," says study co-author Dr. David Dershaw, director of breast imaging at Memorial Sloan-Kettering Cancer Center in New York City. Conversely, says Dershaw, for women at high risk for breast cancer, an MRI screening can be an important tool. "The goal here is to know, going into the screening, who is at high risk and who is not, so you know who will benefit from an MR and who will not," Dershaw says.

Because an MRI can be ultra-sensitive in picking up what looks like breast abnormalities, a false-positive finding can be common in women at low risk for cancer. This, he says, often leads to an unnecessary biopsy. And since biopsies result in scar tissue that can compromise future imaging, the unnecessary treatment is detrimental on two fronts. New York University oncologist Dr. Julia Smith agrees. "As more tests become functionally based, the more scar tissue you have, the more difficult it can be to sort out what is going on," she says. Moreover, says Smith, the psychological and emotional trauma of a false-positive diagnosis can be great. "You don't want to be unnecessarily putting women through something this dramatic unless it's going to have a positive impact on their health and their health care," says Smith, a clinical assistant professor at New York University's School of Medicine.

The new study is a retrospective look at the medical records of 367 women at high risk for breast cancer. None of the women reported any symptoms, and each had a normal mammogram result. These same women subsequently underwent their first MRI screening. It was during the MRIs that breast abnormalities were discovered. Ultimately, a diagnosis of "probably benign" was given to 89 of the 367 women who had the MRI -- equal to about 24 percent. After a second follow-up MRI (on average within 11 months), 20 women had biopsies. Of those 20 women, malignancies were found in 9, constituting 45 percent of the women who underwent biopsy and 10 percent of the original 89 diagnosed with "probably benign" lesions.

The bottom line: "The study showed that women at high risk for breast cancer would benefit from an MR, but women at low or normal risk would not," Dershaw says. Further, he says that knowing a woman's risk profile before MRI screening is the best way to determine how accurate that diagnosis will be. Smith says it's this kind of information that ultimately will give every woman the opportunity to get the most accurate screening result possible, regardless of her risk status. "This study was the first step towards establishing a more personalized screening criteria, one from which all women ultimately will benefit," says Smith.

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Elderly Do Well After Breast-Sparing Cancer Surgery-(Reuters Health-12/06/2003)

Older breast cancer patients who undergo surgery that spares the breast may enjoy a better quality of life than those who have a mastectomy, a new study suggests. According to the study authors, older age has not been considered a deterrent to breast-sparing surgery, but research suggests older women are less likely to receive this more conservative treatment. They say their findings suggest doctors should offer older women the breast-sparing approach as a "reasonable alternative" to mastectomy more often than they traditionally have.

For the study, Dr. J. C. J. M de Haes, of the Academic Medical Hospital in Amsterdam, the Netherlands, studied survival, treatment preference and quality of life among patients having either a mastectomy or removal of the tumor only. Women in the latter group were also treated with the drug tamoxifen. All patients were at least 70 years old. The authors found that although there was no difference in survival between the two groups, those who got breast-sparing surgery had fewer arm problems and tended to have a more positive body image. And more of these patients thought the treatment they received was preferable to the alternative -- 72 percent, versus 62 percent in the mastectomy group. The findings are published in the European Journal of Cancer. "The results of this study," the authors conclude, "suggest that surgeons should propose (tumor removal) and tamoxifen to older breast cancer patients as a reasonable alternative to mastectomy in a more systematic manner than is currently the case."

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Cancer May Spread Earlier Than Thought-(HealthDayNews-09/06/2003)

Individual breast cancer cells may escape from the original tumor and travel to other parts of the body at an earlier stage than originally thought. This finding from German researchers, which appears in this week's issue of the Proceedings of the National Academy of Sciences, could change the way health experts think about approaches to cancer. "It's definitely a new paradigm," says Christos Patriotis, an associate member of the Fox Chase Cancer Center's department of medical oncology in Philadelphia. "There's always been a suspicion among scientists that advanced metastatic disease is not necessarily the same disease as the primary disease."

The classic paradigm for cancer metastasis holds that cells in the primary tumor undergo a long series of genetic changes before leaving that tumor and heading off to other parts of the body. "So far, we have thought that probably the most advanced cell within the primary tumor will leave the primary site and found a metastasis," says study author Dr. Christoph Klein. The new research, which focused on breast cancer but could apply to other types of cancer, raises the possibility that there are actually two different routes by which the disease can spread: the classic one and this entirely new way. The idea could affect how doctors find metastatic cancer, which is cancer that has spread from one part of the body to another. "Many people are using primary tissue from the original breast tumor and exploring it, looking for indicators of spread. And what this [the new research] says is the changes you find in that breast tissue cancer may, in fact, not be the full changes that you get when there's metastatic disease," says Dr. Clifford Hudis, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York City. "The genetic changes that scientists have been looking for may not occur until late in the game, so don't be surprised when your preliminary looks at genetic instability don't yield impressive results. It is really interesting and it's not what anybody expected," Hudis adds.

The new concept also has implications for treatment. "In most of the cases where there is a very clear in situ disease [one that has not spread], then the strategy is to have minimum surgery and treatment, as little as necessary," Patriotis says. "You treat the primary disease and ignore any other disease that has already escaped because you believe there is no such disease." But in breast cancer and also prostate cancer, there have been cases where the initial cancer is seemingly "cured," yet a secondary tumor develops years later. "We see cases where we treat the primary disease, we think that we are clean and out, then three to four years down the line we get relapses with metastatic disease," Patriotis explains.

Ideally, the study authors say, treatment should take into account any differences between primary tumors and cells that have dispersed. "We think if you want to perform adjuvant therapy you have to know the characteristics of the target cells," Klein says. "Clinicians are administering drugs to patients to kill these [metastasized] cells but they don't know anything about them. That was why we decided to investigate these cells."

Klein and his colleagues at the Institut fur Immunologie, Ludwig-Maximilians Universitat in Munich, took bone marrow from breast cancer patients and analyzed individual cells that had migrated to the marrow from the primary tumor. The sample group included both patients whose cancer had spread or metastasized and those whose cancer was still localized. "We were quite surprised about the genetic findings," Klein says. "It seems that the cells leave the primary tumor very, very early. We found [the dispersed cells] had even less changes than the primary tumor, meaning they leave at an early stage of genetic development, even before the primary tumor has accumulated certain changes." The majority of these wandering cells won't develop into a tumor, but there's always that potential. "That's why time is against us," Patriotis says. "The longer you live and the longer you have those cells around, the higher the risk that cells will accumulate the necessary mutations and really take off to become tumors."Which is why it's vital to find them as quickly as possible. The results of this study may lead to new clinical practices, such as sampling bone marrow even when a patient has localized disease.

"Their [the study authors'] point is that looking for genetic indicators of metastatic potential might not help us much right now because genetic changes might occur late in game," Hudis says. "We have to look differently." There may also be a drive to find new signs of single metastatic cells in patients with early-stage cancer, Patriotis adds. Researchers would then need to see if the drugs that are used on primary tumors will also be effective on these errant cells. "Companies that develop new therapies should try to validate whether or not their compounds can work on these cells," Klein says. "They cannot rely on the data of the primary tumor." Investigations are already under way to see if the same process is at work in other cancers, such as prostate cancer, Klein says.

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UK Breast Cancer Cases at Record Levels-(Reuters Health-02/06/2003)

The number of British women diagnosed with breast cancer each year has reached its highest level ever, topping 40,000 for the first time, according to new figures released on Monday by a leading charity. Cancer Research UK said the number of cases would keep increasing for some time, but screening and improved treatments meant more women are being successfully treated than ever before. Currently, three out of four women diagnosed with the disease survive for five years or more, and annual death rates have dropped 21 percent over the past 10 years to around 13,000 in 2001.

"Tamoxifen has been in use for 20 years and the screening program has been up and running for the last 15. These two advances alone account for significant improvements in survival," said Professor Jack Cuzick, head of Cancer Research UK's epidemiology, mathematics and statistics department at the Wolfson Institute for Preventive Medicine in London. He said the reasons for the increasing number of cases were harder to understand, but were related to levels of the female hormone estrogen. "We know that obesity in post menopausal women is a risk factor and that it can raise the levels of estrogen. We also know that levels of obesity have been rising steadily in the past decade and this may be contributing to the upward trend."Genes also play a role, as do late menopause and the early onset of periods, which can also increase exposure to the hormone, he said.

The charity's clinical director Professor Robert Souhami said research was beginning to uncover the factors that affect risk. "In the meantime, early detection remains very important in preventing deaths from breast cancer and it is essential that women are aware of this and attend for screening when they are invited."

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The Use of Taxotere(R) in Treating Breast Cancer Highlighted at American Society of Clinical Oncology Annual Meeting-(MARKET WIRE-02/06/2003)

TaxotereŽ (docetaxel) Injection Concentrate, an active chemotherapy agent, shows positive results in various treatment regimens in early and advanced breast cancer according to numerous phase II and III clinical studies presented at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO). Among the studies involving TaxotereŽ at this year's ASCO, several focused on the use of TaxotereŽ to treat women with early stage breast cancer before (neoadjuvant) or after (adjuvant) surgery, as well as women with advanced disease.

Improvement in Disease-Free Survival with Adjuvant TC: Three-year results of a prospective, randomized trial of adjuvant therapy among patients with stage I-III operable, invasive breast cancer showed a 21 percent reduction in the risk of recurrence in patients given TaxotereŽ and cyclophosphamide (TC) versus those given doxorubicin and cyclophosphamide (AC). At a median follow-up of 43 months, TC was also better tolerated than the standard AC adjuvant regimen. "Since many patients are unable to receive anthracycline-based chemotherapy, it is important that we try to establish the efficacy and tolerability of non-anthracycline-based adjuvant regimens for the treatment of breast cancer, especially in early stage disease.

The trial included 1,016 patients who were randomized to receive either four courses of the standard dose of AC, 60/600-mg/m2, or four courses of TC, 75/600-mgs/m2, each given every three weeks preceding adjuvant radiation therapy and tamoxifen if indicated.

Benefits in First-Line Treatment of Metastatic Breast Cancer: Researchers from the Magee-Women's Hospital and the University of Pittsburgh Cancer Institute also reported phase II study results that showed the combination of TaxotereŽ, carboplatin and traztuzumab (herceptin) (TCH) is an extremely effective first-line treatment for Her 2 Neu (+) metastatic breast cancer (MBC). Forty previously untreated patients with MBC participated in this study.

TCH was administered on day one every three weeks for up to nine cycles. Evaluation of responses was done after three and six cycles. The overall response rate was 82 percent and the overall one-year survival was 93 percent. Thirty-seven percent of patients had a complete response (CR) and 45 percent showed partial response (PR). Fourteen percent of patients had stable disease (SD) after chemotherapy, and three patients maintained their SD for more than six months. Seventeen patients with a CR, PR or SD are still being followed. In four patients, there was no evidence of progression for greater than 30 months.

"Previous studies suggest a synergy between TaxotereŽ, carboplatin and traztuzumab. The findings of this study confirm that the TCH combination resulted in a response rate among the highest yet achieved for Her 2 Neu positive metastatic breast cancer. These findings are extremely encouraging, and we hope will lead to a new, effective treatment option for advanced breast cancer patients," said study author Adam Brufsky, MD, PhD, assistant professor of medicine and director of the Magee Breast Program of the University of Pittsburgh Medical Center Cancer Centers. "The high response rate seen in this patient population may have positive implications for the use of TCH as adjuvant non-anthracycline containing chemotherapy for early-stage Her 2 Neu positive breast cancer as well."

Additionally, researchers from North Central Cancer Treatment Group presented favorable phase II study results that showed the combination of TaxotereŽ and carboplatin is an active regimen that provides comparable efficacy to other combination regimens used in the treatment of MBC with low levels of serious neurotoxicity. Fifty-three patients with MBC were enrolled in the study. TaxotereŽ and carboplatin was administered on day one every three weeks. Median number of treatment cycles completed was six. The overall response rate was 60 percent and the one-year survival rate was 64 percent. The median time to progression was 9.8 months with median survival not yet reached (33 of 53 patients are still alive as of April 2003). Six patients are still receiving treatment on this study protocol. Notably, ninety-six percent of patients did not experience serious neurotoxicity (grade 3/4) during treatment.

"The results of this study show that TaxotereŽ plus carboplatin is a very active regimen as a first-line therapy for metastatic breast cancer with low levels of neurotoxicity," said Edith A. Perez, MD, Professor of Medicine, Mayo Medical School, and Director, Breast Cancer Program and the Cancer Clinical Study Unit, Mayo Clinic in Jacksonville, Florida. "The combination warrants further investigation in metastatic breast cancer as well as in the neoadjuvant setting."

Survival Benefits and High Response Rates Seen With Taxotere in Neoadjuvant Setting: Updated response and survival data from a multi-center study examining the use of TaxotereŽ in the neoadjuvant setting showed a high pathological complete response (pCR) rate of 10 percent (breast + axilla). In this phase II study, patients with stage III breast cancer were treated with four cycles of TaxotereŽ followed by surgery and adjuvant doxorubicin and cyclo-phosphamide.

Patients were evaluated for both clinical response (tumor reduction) and pathological response (microscopic analysis of breast tissue). A pathological complete response indicates that the tumor is no longer present in the breast or the adjacent lymph nodes. At a median follow-up of five years, the disease free survival among the 42 patients eligible for response was 79 percent and overall survival was 81 percent.

About TaxotereŽ: TaxotereŽ, a drug in the taxoid class of chemotherapeutic agents, inhibits cancer cell division by essentially "freezing" the cell's internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. TaxotereŽ promotes their assembly and blocks their disassembly, thereby preventing cancer cells from dividing and resulting in cancer cell death. TaxotereŽ is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with cisplatin, who had not received prior chemotherapy. It also is approved for patients with locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy.

The most common severe side effects associated with TaxotereŽ include low blood cell count, fatigue, fluid retention and mouth sores. The most common non-severe side effects included hair loss, neurosensory, cutaneous, nail changes, nausea and diarrhea. These side effects are generally reversible and manageable. A premedication regimen with corticosteroids is recommended in order to prevent or reduce hypersensitivity and fluid retention. TaxotereŽ is not appropriate therapy for patients with significant liver impairment or a low white blood cell count. Patients 65 years of age or older may experience some side effects more frequently.

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Early Puberty Linked to Breast Cancer(HealthScoutNews-04/06/2003)

Early puberty makes some women more likely to develop breast cancer later in life, says a study that provides new clues in the ongoing hunt for genes involved in the disease. Those as yet unknown genes seem to make women more sensitive to the ill effect of hormones at one important time of life, puberty, explains study author Ann S. Hamilton, an assistant professor of preventive medicine at University of Southern California Keck School of Medicine. Female hormones are known to be involved in the risk of breast cancer, Hamilton says, and research has focused on the effects of lifetime exposure. The new study results indicate the hunt should also include genes that affect "this critical time period, genes that make hormones more important at that time."

Hamilton and another Keck faculty member, Dr. Thomas M. Mack, made that finding with 1,811 pairs of female twins, one or both of whom had breast cancer. Some were identical twins with the same set of genes, some were fraternal twins whose genes differed slightly. They were questioned about a number of factors that could affect breast cancer risk -- number of children, age when the first child was born, age of menopause, and age of puberty. Among the 209 pairs of identical twins who both had breast cancer, the one who began puberty earlier was more than five times as likely to get breast cancer first. Indicators of puberty were first menstruation, when menstruation became regular, and breast development. The effect was strongest for the women who began menstruating before age 12, says a report in the June 5 issue of the New England Journal of Medicine.

What's true for these twins is probably true for some other women, Hamilton says. "Women with this particular genetic susceptibility are affected at the time of puberty," she says. "And the gene-environment interaction is strongest when puberty occurs earlier." A couple of genes, designated BRCA1 and BRCA2, are known to increase the risk of breast cancer, Hamilton says, but there are a number of reasons to believe they are not responsible for the puberty effect. Hamilton and Mack have begun to study possible genetic factors in the twins, a study that promises to be a long one, she says.

The study is "very provocative, something that should be followed up," says Patricia Hartge, deputy director of the epidemiology and biostatistics program at the National Cancer Institute, who wrote an accompanying editorial. There is room for a shade of doubt, because the number of women in the study was relatively small, Hartge says, but she believes "the puberty finding will hold up." It was an ingenious idea to study twins, Hartge says. "They understood that if you have identical twins and they both develop breast cancer, they probably have some of the genes we are looking for." Now comes the hard part, Hartge says: finding the genes. "We don't know what those genes are," she says. "In the next stage of research, we want them to be identified."

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Predicting Breast Cancer on a Molecular Level-(HealthScoutNews-03/06/2003)

The Mayo Clinic will lead a national study to search for molecular predictors of breast cancer. The scientists intend to research biomarkers that may help identify women with benign breast disease who are at risk for developing breast cancer. Women who have a breast biopsy with benign findings are defined as having benign breast disease. "We know that some women with benign breast disease have an increased risk of eventually developing breast cancer and that the cancer can occur in either breast," principal investigator Dr. Lynn Hartmann says in a news release. "What we lack are good research studies that identify these women so they can receive the necessary screening and risk-reduction strategies," Hartmann says.

Each year, more than 200,000 women in the United States are diagnosed with benign breast disease. But few tests can pinpoint which women have a greater risk of developing breast cancer. This study will examine benign tissue specimens taken from 700 women who had breast biopsies at the Mayo Clinic between 1967 and 1991 and later developed breast cancer. Their tissue samples will be compared to benign tissue samples taken over the same time period from 700 other women who didn't develop breast cancer. The researchers will compare molecular tissue markers in the tissue samples from the two groups of women.

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Femara(R) Demonstrated Early Survival Advantage Over Tamoxifen in Advanced Breast Cancer-(MARKET WIRE-29/05/2003)

The largest study ever to evaluate a hormonal therapy in advanced breast cancer demonstrated that FemaraŽ (letrozole tablets) showed superior time to disease progression, objective tumor response rate, and reported an early survival advantage, compared with tamoxifen in postmenopausal women with locally advanced or metastatic breast cancer. The study was published in the June 1, 2003, issue of the Journal of Clinical Oncology (JCO). The data are from a Phase III study evaluating Femara and tamoxifen as first-line treatments in patients with advanced breast cancer. They show that, compared with tamoxifen, Femara demonstrated higher one- and two-year survival rates.

The study included a cross over to the alternate therapy if patients were deemed to be appropriate candidates for further treatment with hormonal therapy. Thus, an analysis was done to isolate the impact of first-line therapy. This showed patients treated on Femara survived 12 months longer than those treated with tamoxifen. Femara, a leading aromatase inhibitor, is a once-a-day oral, first-line treatment for postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. It is also approved for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. "Demonstrating a survival advantage has been an important goal of breast cancer research for a long time," said Henning Mouridsen, M.D., Rigshospitalet Department of Oncology, Copenhagen, Denmark. "Now that we have evidence that Femara offers a significant early survival advantage over tamoxifen in the first-line setting, it may become the standard of care for patients in whom hormonal therapy is appropriate."

The randomized, double blind study of 907 postmenopausal women was designed to compare Femara (453 patients) with tamoxifen (454 patients) as first-line therapy in women with locally advanced or metastatic breast cancer. Survival rates at one and two years show Femara offers a statistically significant survival advantage compared with tamoxifen (1 year P=0.004; 2 years P=0.02). The median overall survival for Femara was 35 months vs. 32 months for tamoxifen (P=0.514). At the discretion of the investigator, the study design allowed patients to cross over to the other therapy upon progression. Approximately 50% of all randomized patients remained on the same therapy throughout the study. At the end of the trial (median follow-up of 32 months), 48% of the patients receiving first-line Femara remained free of tumor progression, compared with 27% of the patients receiving first-line tamoxifen. In addition, the odds of responding to treatment were 78% greater with Femara (P=0.0002) than with tamoxifen, and the risk of progression was 28% less with Femara than with tamoxifen (P < 0.0001).

Equally important, patients treated with Femara rather than tamoxifen experienced a significantly longer interval until they needed chemotherapy (median time-to-chemotherapy 16 vs. 9 months, P=0.005). The reported data also confirm earlier findings that use of Femara significantly delayed progression of the disease for a median of 9.4 months, compared with a median of 6.0 months for tamoxifen (P < 0.0001).

As breast cancer advances, it often affects a woman's ability to function and perform routine daily activities. In the reported trial, researchers measured women's daily performance by using the Karnofsky Performance Score, a standard clinical measurement tool based on a 100-point scale (100 being the top performance point). A change of 20 points or more on the KPS-scale is considered clinically relevant. The investigators found that significantly more women taking Femara were able to maintain their original level of performance for a longer period of time than those treated with tamoxifen.

Femara is contraindicated in patients with known hypersensitivity to Femara or any of its excipients. Femara is generally well tolerated and adverse reaction rates in the first-line study in which Femara was compared with tamoxifen were similar with those seen in second-line studies. The most commonly reported adverse events for Femara vs. tamoxifen were bone pain (22% vs. 21%), hot flushes (19% vs. 16%), back pain (18% vs. 19%), nausea (17% vs. 17%), dyspnea or labored breathing (18% vs. 17%), arthralgia (16% vs. 15%), fatigue (13% vs. 13%), coughing (13% vs. 13%), constipation (10% vs. 11%), chest pain (6% vs. 6%) and headache (8% vs. 6%).

Femara may cause fetal harm when administered to pregnant women. There is no clinical experience to date on the use of Femara in combination with other anticancer agents. The incidence of peripheral thromboembolic events, cardiovascular events, and cerebrovascular events was 3-4% in each treatment arm.

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Cancer Drug's Heart Risk Underestimated-(HealthScoutNews-19/05/2003)

Doctors have known a common cancer drug causes heart failure in some patients, forcing them to stop treatment and in rare cases requiring an organ transplant, but a new study says that risk may be significantly greater than previously believed. The drug, doxorubicin, is used in the treatment of many cancers, from leukemia and breast tumors to lung and testicular cancers. The new research doesn't second-guess the therapy. However, experts say it should prompt cancer specialists to be especially vigilant about budding congestive heart failure, particularly in patients most vulnerable to the problem, such as children, the elderly and those who've had radiation therapy. "What this paper has demonstrated is that while we thought we had a pretty good idea of exactly what the risks are of doxorubicin, we have to be a little more cautious" in using it, says study co-author Dr. Michael Ewer, a heart expert at the University of Texas' M.D. Anderson Cancer Center. "If you have signs of decreasing function then you do need to stop the drug right away, but that's usually a little later than you wished you would have stopped it."

A report on the findings appears in the June 1 issue of Cancer. The work was funded by Pharmacia, which makes a version of doxorubicin called Adriamycin. Ewer's group, led by Dr. Sandra Swain of the National Cancer Institute, reviewed three earlier studies of doxorubicin, also known as Rubex, and heart failure in patients with lung and breast cancer. Of the 630 subjects, 32 were diagnosed with congestive heart failure. The risk of the complication rose with the cumulative dose of the drug. Heart failure occurred in 1.7 percent of patients taking a low dose -- measured in milligrams per meters squared -- but it occurred in 26 percent of people on a moderate to high regimen. Nearly half of patients on the highest doses developed the condition.

The overall rate of heart failure in people on doxorubicin was roughly 5 percent at a medium dose, higher than the rate reported in the most recent study to examine the effect. In addition to the greater prevalence of heart problems, Ewer's group noted two other areas of concern with the cancer drug. People over age 65 were about 20 percent more likely than younger patients to suffer the complication. And a heart output test doctors have been using to monitor heart function in people taking doxorubicin doesn't seem to be of much use. Some patients with no problems have abnormal test results, while others with failing pumps go undetected. "It's just an imperfect test," Ewer says

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