BREAST CANCER

Breast Cancer in Pregnancy: Chemo OK. Researchers Say Aggressive Treatment Is Safe for the Babies of Pregnant Women (WebMD Medical Newsv - 18/04/2008)


Facing a diagnosis of breast cancer is challenging enough, but facing breast cancer during pregnancy can be nothing short of devastating. Can I have chemotherapy? Will the treatment hurt my baby? New research helps to answer these questions, and the findings should serve to reassure patients and their doctors. In a German study examining outcomes among 122 pregnant breast cancer patients, researchers concluded that pregnant patients can often be treated as aggressively as 
non-pregnant patients, with little evidence of ill effects to their babies. The findings were presented this week at the 6th European Breast Cancer Conference in 
Berlin. Sibylle Loibl, MD, of the University of Frankfurt, tells WebMD that it is now clear that most pregnant breast cancer patients do have options. "The evidence now shows that women who are pregnant are often good candidates for standard breast cancer treatments," she says. 

Breast Cancer and Pregnancy 

The patients in the study were enrolled in a registry of women diagnosed with breast cancer while pregnant. All were diagnosed between April 2003 and December 2007. Their average age at diagnosis was 33 and the average gestational age of their babies was 21 weeks. While a few women terminated their pregnancies, most did not, Loibl says. A total of 33% had surgery alone, 43% had surgery and chemotherapy, 5.4% had chemotherapy alone, and 2.7% had no treatment. The health problems reported among the babies during their first month of life were generally minor and outcomes among babies born to mothers who had chemotherapy were similar to those of babies born to mothers who did not. Loibl adds that some of the children in the registry have now been followed for five years, with little evidence of developmental delays or learning issues.

Chemotherapy During Pregnancy

Much of the pioneering research on breast cancer treatment during pregnancy has been done over the past two decades at Houston's University of Texas M.D. Anderson Cancer Center. M.D. Anderson clinicians were among the first to treat pregnant women with standard chemotherapy protocols. Some of the children born to these women are now in their late teens, and oncologist Jennifer Litton, MD, tells WebMD they are doing quite well. "There haven't been significant cardiac effects or learning disabilities," she says. Chemotherapy is not given at M.D. Anderson during the first trimester of pregnancy, when vital organs are still forming and the risk of birth defects is highest. "The birth defect rate is as high as 20% when chemotherapy is given in the first trimester, but that rate drops to around 1.3% when chemotherapy is given later," she says. "That is on par with the national average," she says. Chemotherapy-treated patients usually get a combination of three drugs -- fluorouracil, doxorubicin, and cyclophosphamide.

The American Cancer Society estimates that about one in 3,000 pregnant women are 
diagnosed with breast cancer, and the number is expected to grow as more women have babies in their late 30s and 40s, says Litton. Litton agrees that pregnant breast cancer patients usually do have options, but they may not hear about them unless they are treated at a major cancer center like M.D. Anderson. "Studies like this one are getting the message out to community physicians, but it is slow," she says. "This is a case where seeking a second opinion may make a big difference."

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Novel Xeloda(R) Dosing Schedule May Offer Well-Tolerated Alternative For Treatment Of Advanced Breast Cancer ( Yahoo News- 19/04/2008)


A novel biweekly dosing schedule of Xeloda(R) (capecitabine) enabled safe delivery of higher daily doses in the treatment of advanced breast cancer, according to an investigational study published in the April 10, 2008 issue of the Journal of Clinical Oncology. The data showed that a seven-days-on/seven-days-off (7-on/7-off) regimen, called "dose dense," was generally well-tolerated up to 2,000 mg twice daily (4,000 mg/day), providing a potential alternative to the standard Xeloda dosing of 14 days on and seven days off (14-on/7-off). "As we predicted using the Norton-Simon mathematical model -- the basis for the dose dense approach to therapy that was pioneered at MSKCC -- these results demonstrate that a biweekly regimen of capecitabine appears to be well-tolerated, at dosing levels that are higher than previously thought possible," said Tiffany A. Traina, M.D., a medical oncologist in 
the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and lead author of the study. "We're currently conducting later-phase trials to determine the efficacy of this 7-on/7-off dosing schedule." Efficacy of the 7-on/7-off schedule using Xeloda is being determined in a Phase II clinical trial 
program in patients with advanced breast cancer and is also being tested in combination with Avastin(R) (bevacizumab).

Breast cancer is the most common cancer among women, other than skin cancer. According to the American Cancer Society (ACS), about 182,460 women in the United States will be found to have invasive breast cancer in 2008. Breast cancer is the second leading cause of cancer death in women, after lung cancer -- about 40,930 women will die from the disease this year. Metastatic breast cancer, or cancer that has spread from the breast to other parts of the body, has an especially poor prognosis, with a five-year survival rate of 27 percent. Currently, there are two and a half million breast cancer survivors in the United States. According to the ACS, breast cancer death rates are going down; the decline may be the result of early detection and treatment.

About the Study

Prior to study initiation, the Norton-Simon mathematical model (Norton et al, AACR 2005) -- which explores how the growth characteristics of a cancer affect response to chemotherapy -- was applied to determine that the maximum impact of Xeloda treatment in breast cancer patients occurs after seven days. Based on this finding, the single-center, open-label phase I/II trial was designed to determine the maximum tolerated dose (MTD) of Xeloda administered orally for seven days, followed by a seven-day rest (7-on/7-off), in patients with advanced-stage breast cancer. MTD was defined as the highest dose for which the incidence of dose-limiting toxicity (DLT) is less than 33 percent. DLT was defined as grade 3/4 hematologic toxicity lasting greater than two weeks despite growth factor support, or any grade 3/4 nonhematologic toxicity.

The Phase I study dose escalation scheme was a standard "3+3" design, using flat dosing that begins at 1,500 mg twice daily and increases by 500 mg/dose level until the MTD is reached. All patients in a cohort were observed for 28 days before enrollment to the next level is permitted to monitor for delayed toxicity. The study showed that the dose dense regimen was well-tolerated in patients with advanced 
breast cancer, allowing safe delivery of higher daily doses than routinely used in practice. Of the 21 patients recruited for the trial, 18 were treated with Xeloda and reached a maximum tolerated dose of 2,000 mg twice daily. There were no grade 4/5 toxicities and grade 3 toxicities (which included one dose-limiting incident of hand-foot syndrome at 2,000 mg twice daily and two at 2,000 mg/2,500 mg, and one dose-limiting incident of diarrhea at 2,000 mg/2,500 mg) were transient and medically manageable. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29 percent), leukopenia/neutropenia (24 percent) and fatigue (19 percent).

About XELODA (capecitabine)

Xeloda is the only FDA-approved oral chemotherapy for both metastatic breast cancer and adjuvant and metastatic colorectal cancer. Inactive in pill form, Xeloda is enzymatically activated within the body; when it comes into contact with a naturally occurring protein called thymidine phosphorylase, or TP, Xeloda is transformed into 5-FU, a cytotoxic (cell-killing) drug. Because many cancers have higher levels of TP than does normal tissue, more 5-FU is delivered to the tumor than to other tissue.
A clinically important drug interaction between Xeloda and warfarin has been demonstrated; altered coagulation parameters and/or bleeding and death have been reported. Clinically significant increases in prothrombin time (PT) and INR have been observed within days to months after starting Xeloda, and infrequently within one month of stopping Xeloda. For patients receiving both drugs concomitantly, frequent monitoring of INR or PT is recommended. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.
Xeloda is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil, and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Xeloda is contraindicated in patients with severe renal impairment. For patients with moderate renal impairment, dose reduction is required. The most common adverse events (greater than or equal to 20%) of Xeloda monotherapy were diarrhea, nausea, stomatitis and hand-foot syndrome. As with any cancer therapy, there is a risk of side effects, and these are usually manageable and reversible with dose modification or interruption.

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Acupuncture eases hot flushes in breast cancer patients taking tamoxifen (Yahoo News - 19/04/2008)

Acupuncture can effectively ease hot flushes among women taking anti-oestrogen tamoxifen after breast cancer surgery, says a new study. Mrs Jill Hervik, a physiotherapist and acupuncturist at the Vestfold Central Hospital (Tonsberg, 
Norway) revealed that patients who received traditional Chinese acupuncture had a 50 pct reduction in hot flushes, both during the day and the night, and that this effect continued after the acupuncture ceased. Hervik along with supervisor, Dr Odd Mjoland conducted single-blind, controlled trial on 59 postmenopausal breast cancer patients. They were either given ten weeks of traditional Chinese acupuncture or sham (minimal) acupuncture between March 2003 and December 2006. All were taking tamoxifen following the surgery. Mrs Hervik delivered both the real and the sham acupuncture to the patients, and maintained a neutral treatment atmosphere.

Both the acupuncture and the sham acupuncture were given twice a week for the first five weeks and then once a week for the next five weeks. "Acupuncture is increasingly used in western countries to treat the problem of hot flushes in healthy post-menopausal women, so we wanted to see whether it was effective in women 
with breast cancer suffering from hot flushes as a result of their anti-oestrogen medication," said Mrs Hervik. The patients were asked to record the number of hot flushes they experienced for four weeks before the treatment, during the treatment and during a 12-week follow-up period. The real acupuncture was given using needles inserted at varying depths to a maximum of 3cms at several well-known acupuncture points. For the sham acupuncture, the needles were not inserted so deep (a maximum of 3mm) and in places well way from acupuncture points.

"During the treatment, hot flushes were reduced by 50 percent, both day and night, in the acupuncture group," Mrs Hervik said. "Three months after the last treatment a further reduction was seen. No significant changes were seen in the sham group during the day. At night there was a slight reduction during the treatment period but, once treatment had ceased, the number of hot flushes increased again. "Acupuncture has two advantages over other treatments for hot flushes: it is cheap and does not cause adverse side-effects," she added. 

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Standard Chemo Works Better Against Metastatic BRCA1/2 Breast Cancer Than Against Sporadic Tumors (Yahoo News- 20/04/2008)

The first study to investigate the effects of chemotherapy on metastatic breast cancer in women with the BRCA1 or BRCA2 gene mutation has shown that standard chemotherapy works better in these patients than in women without the BRCA1/2 mutation. The authors of a study presented at the 6th European Breast Cancer Conference (EBCC-6) in Berlin found that women with BRCA2-associated breast cancer had a significantly higher response rate, a longer time without the disease progressing, and a longer overall survival when treated with anthracycline-based regimens than did women with sporadic breast cancers that were not associated with BRCA1/2. Women with BRCA1-associated breast cancer also did better than women with sporadic breast cancer, but the rates were not statistically significant. 
Researchers at the Daniel den Hoed Cancer Centre/Erasmus Medical Centre (Rotterdam, The Netherlands) conducted the study. They matched 112 women with BRCA1-associated metastatic cancer and 29 women with BRCA2-associated metastatic cancer with 141 women with sporadic breast cancers. The women had been treated with anthracycline-based or taxane-based regimens, CMF (cyclophosphamide, methotrexate and fluorouracil 5FU) or other chemotherapy regimens. BRCA2 women had a higher response rate to chemotherapy (89% versus 50%), a longer progression-free survival (nearly a third better) and a longer overall survival (47% better) than did women with sporadic cancers. When the researchers looked more closely at the type of chemotherapy the women had received, they found that the improved progression-free survival mainly occurred in patients on anthracyclines and disappeared for those treated with CMF. 

The lead author of the study, Dr Mieke Kriege, an epidemiologist and project researcher at the Rotterdam Family Cancer Clinic, said: "It is difficult to make firm conclusions about response to different treatments from our results so far, but it does seem that the higher sensitivity to treatment by BRCA2-associated patients is especially caused by the anthracycline regimen." The project leader, Professor Jan Klijn, medical oncologist and chairman of the Rotterdam Family Cancer Clinic, said: "Our findings show that various standard chemotherapy regimens are clinically effective in the treatment of metastatic BRCA1/2-associated breast cancer. The observation of the high efficacy of anthracycline-based regimens is especially reassuring. However, we would like to emphasise that larger, additional studies are urgently needed to investigate further newer regimens containing taxanes and platinum compounds." Dr Kriege said: "Currently, there are very few studies on the efficacy of chemotherapy in BRCA1/2-associated breast cancer - mainly a few, very small studies with less than 44 patients in the neo-adjuvant setting. Our study is the only one in metastatic disease and, with 141 BRCA1/2 gene mutation carriers included, it is by far the largest study in the world." 

The authors believe that an explanation of why chemotherapy seems to work better in BRCA1/2 breast cancers than in sporadic cancers is due to the lack of a working BRCA1/2 protein. "Functional BRCA1 and BRCA2 proteins are involved in DNA repair," said Dr Kriege. "Most chemotherapeutic agents are active by damaging DNA (especially anthracycline-based regimens). In BRCA1 and BRCA2 mutation carriers, who have no functional BRCA1 and BRCA2 proteins respectively, DNA repair after chemotherapy might be worse than in sporadic patients resulting in better treatment responses. Pre-clinical studies showed that BRCA1 and BRCA2 mutated cells are especially sensitive to chemotherapeutic agents that cause double-strand DNA breaks (such as anthracyclines and platinum)." The researchers now plan to investigate the effects of adjuvant and neo-adjuvant treatments in women with BRCA1/2-associated breast cancers, and to evaluate taxane and platinum therapies further. 

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Falling breast cancer rates seen only in whites (Reuters - 15/04/2008) 

New research shows a sharp drop in U.S. breast cancer cases in recent 
years was limited to white women, possibly because they abandoned hormone replacement therapy in greater numbers than minority groups. Many women stopped using hormone replacement therapy after a large study suggested in 2002 that the combination of estrogen and progestin used to treat menopause symptoms 
raised the risk of breast cancer and heart disease. White women had been more likely to use hormone therapy, and were also the most likely to abandon the drugs after U.S. regulators warned about the cancer link in 2003, according to Dr. 
Dezheng Huo of the University of Chicago and the study's lead investigator. "The sharp reductions seen in Caucasians aged 50 to 69 years were not seen among other ethnic groups," Hou told the American Association for Cancer Research.
According to the American Cancer Society, the overall incidence of female breast cancer fell 3.9 percent a year from 2001 through 2004. The researchers said the decline has been mainly among women older than 50 with estrogen-receptor positive cancer.

Using data from the National Cancer Institute's database, they calculated breast cancer rates between 2000 and 2004 to determine whether or not the trends were similar across racial and ethnic groups. The researchers found that in the first two years, the rate of invasive breast cancer among whites was stable. However, toward the end of 2003, it started falling by as much as 2.4 percent per quarter while continuing to grow by 0.7 percent per quarter among black women. Rates for American Indians and Alaskan Natives fell 0.14 percent and among Asian Americans by 0.46 percent. "The finding ... suggests that exogenous estrogen serves as a promoter rather than an initiator of breast cancer," the researchers said.

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Radiation Beneficial For Older Breast Cancer Patients (Yahoo News- 12/04/2008)


A breast cancer patient's age alone should not determine whether or not she receives 
standard breast-conservation treatments, including a lumpectomy and radiation therapy; however, if additional health problems (comorbidities) are present, treatments should be individualized based on age and the type of comorbidities, according to a study in the April 1 edition of the International Journal for Radiation Oncology Biology Physics, the official journal of the American Society for Therapeutic Radiology and Oncology. The occurrence of breast cancer in women increases as women age. According to the National Cancer Institute's SEER Cancer Statistics Review, women between the ages of 75 and 79 have the highest incidence of breast cancer diagnoses at 497 cases per 100,000 people. Along with cancer, most women in this age group are dealing with additional health problems. According to a 1999 women's health and aging study in the Journal of Clinical Epidemiology, the majority of older patients diagnosed with cancer have at least one other medical condition and more than half of patients with cancer over the age of 65 have three or more associated medical conditions.

This study, conducted by the departments of Radiation Oncology, Biostatistics and 
Epidemiology, and Medicine, Division of Geriatrics, at the University of Pennsylvania School Of Medicine in Philadelphia, sought to determine the impact of these additional medical problems on breast cancer patients who receive the same standard treatments as patients with no additional medical problems and if old age is a reason to deny some standard treatments. Most randomized trials that compare outcomes of breast-conserving surgery with and without radiation consistently show more positive outcomes when radiation is used; however, most of the trials exclude women older than 70 years old so there is not a lot of data on the impact of radiation on older women. Between 1979 and 2002, 238 women, 70 years old and older, with Stage I or II invasive carcinoma of the breast received breast-conservation therapy and their outcomes were compared by age groups and comorbidities. Most of the patients studied had mild comorbidities.

The researchers found that the number of deaths from breast cancer among the patients studied was similar to the number seen among all age groups of patients without additional medical problems. The researchers also found that the majority of elderly women with early-stage breast cancers and mild comorbidities actually benefited from the use of radiation and had minimal side effects. The overall survival rates for the patients in the five- and 10-year follow-up periods were 80 percent and 50 percent, respectively; however, more deaths during the 10-year period were 
caused by intercurrent diseases than breast cancer. "Doctors need to understand that comorbidities should be the determining factor in deciding an older patient's course of treatment, not age," said Eleanor Harris, M.D., clinical director of radiation oncology at the Moffitt Cancer Center in Tampa, Fla. "There is a sense in the field that elderly women need less treatment than younger women, but we should not be under treating women simply because they have passed the age of 70." ASTRO is the largest radiation oncology society in the world, with 9,000 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to improving patient care through education, clinical practice, advancement of science and advocacy.

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Trans-fats linked to breast cancer risk in study (Reuters- 11/04/2008)


Trans-fats, which are being phased out of food because they clog arteries, may raise the risk of getting breast cancer, European researchers reported on Friday. They found that women with the highest blood levels of trans-fats had about twice the risk of breast cancer compared to women with the lowest levels. "At this stage, we can only recommend limiting the consumption of processed foods, the source of industrially produced trans-fatty acid," the researchers wrote in the American 
Journal of Epidemiology. Trans-fats or trans-fatty acids are made in creating artificially hardened fats -- in the process of hydrogenization, for instance. They were, ironically, meant to be healthful replacements for artery-clogging saturated fats such as butter and lard. But the process of making vegetable oil behave like butter made it as unhealthful as butter. New York and California have banned trans-fats in restaurant foods. Canada and Britain have considered it and countless food companies have dropped them as an ingredient.

Veronique Chajes of the French national scientific research center at the University of 
Paris-South and colleagues studied women taking part in a large European cancer trial. They looked at blood samples collected between 1995 and 1998 from 25,000 women who had volunteered to report on their eating and lifestyle habits and then be followed for years to see if they developed cancer. They studied 363 women diagnosed with breast cancer, comparing their blood levels of fatty acids with those of women without cancer. The higher the levels of trans-fatty acids, the more likely a woman was to have cancer, Chajes and colleagues found. Women with higher levels of omega-3 fatty acids, being studied for their potential benefits to health, were not any less likely to have breast cancer, the researchers found.

Obese women are more likely to develop breast cancer, among other types of cancer, and high-fat diets are also linked with breast cancer. Trans-fats can be found in cooking fats, baked goods, snacks and a variety of other prepared foods. Omega-3 fatty acids are found in fatty fish such as salmon, walnuts and leafy green vegetables.

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Study by American Roentgen Ray Society (Yahoo News- 11/04/2008)

Newly diagnosed breast cancer patients benefit from use of USFNA of lymph nodes
Ultrasound-guided fine needle aspiration (USFNA) of the lymph nodes is a safe, useful, and minimally invasive procedure for diagnosing metastatic disease in patients who are undergoing preoperative staging for breast cancer, according to a recent study conducted by researchers at the Rhode Island Hospital/Warren Alpert Medical School of Brown University in Providence, RI. “We wanted to determine which patients with newly diagnosed breast cancer would benefit most from preoperative fine needle aspiration of the axillary lymph nodes,” said Martha Mainiero, MD, lead author of the study. “This quick and minimally invasive procedure can assist the surgeon in determining what type of axillary surgery is best for patients with breast 
cancer. Unfortunately many centers do not routinely perform this procedure as there is not yet consensus on who will benefit from it,” she said. 

The study consisted of USFNA of axillary lymph nodes in 224 breast cancer patients. The researchers measured the cortical thickness of each lymph node that was aspirated. They found that using a cortical thickness measurement of 3mm to determine who gets USFNA would result in the most optimum combination of diagnosing metastatic disease preoperatively while minimizing unnecessary USFNA. Patients in the study had primary tumor sizes ranging from 0-12 cm with a mean of 1.9cm and included 159 tumors that measured less than or equal to 2 cm and 65 tumors that were greater than 2 cm. The use of USFNA was positive in 52 patients (23%). If USFNA were limited only to axillary lymph nodes with a cortical thickness of 3 mm or more, USFNA positivity would have increased to 49%. “With these results, this procedure may become more widely used and save patients unnecessary surgery,” said Dr. Mainiero. “This cut-off provided the most optimum combination in detecting metastatic disease while minimizing negative USFNA results,” she 
said.

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Alcohol consumption and risk of breast cancer in postmenopausal women: the NIH-AARP Diet and Health Study (Yahoo News- 12/04/2008)

One of the largest studies of its kind has found that alcohol is a substantial risk factor for development of the most common type of breast cancer – the 70 percent of tumors that are classified as positive for both the estrogen and progesterone receptors (ER+/PR+). Researchers report that even moderate alcohol consumption, defined as one or two drinks per day, increased risk of developing this kind of cancer, and the more a woman drank, the higher her risk. Compared to women who did not drink at all, women who had three or more glasses of alcohol daily had as much as a 51 percent increased risk of ER+/PR+ breast cancer. “This suggests that a woman should evaluate consumption of alcohol along with other known breast cancer risk factors, such as use of hormone replacement therapy,” said the study’s first author, Jasmine Q. Lew, a fourth-year medical student at the University of Chicago who is conducting this research as a recipient of the Howard Hughes Medical Institute-National Institutes of Health Research Scholarship at the National Cancer Institute’s (NCI) Division of Cancer Epidemiology and Genetics. 

Lew and her research colleagues from NCI say their analysis could not support a definitive conclusion as to whether alcohol influences development of other breast cancer tumor types. “But we have enough numbers to study alcohol’s influence on ER+/PR+ breast cancer,” she said. Epidemiologic studies have long suggested that use of alcohol may increase a woman’s risk for developing breast cancer, and laboratory studies have shown that alcohol increases the amount of estrogen metabolites available in a woman’s body, which can then act as a fuel for 
hormone-sensitive breast cancer. But few studies have looked at alcohol’s effect on tumor type. In this study, the researchers reviewed data from the NIH-AARP Diet and Health Study, which began in 1995. Lew and her colleagues analyzed 184,418 postmenopausal women who enrolled in this cohort study, and who answered questions about their daily alcohol consumption. During an average of seven years of follow-up, they found that 70 percent of women in the study drank alcohol; the average amount was a little less than a drink a day. Overall, the authors found that moderate drinking in women increased risk of developing breast cancer. They then identified 5,461 cases of invasive breast cancer, for which they had tumor type information on 2,391 cases. In all, they analyzed data on 1,641 ER+/PR+, 366 ER-/PR-, 336 ER+/PR-, and 48 ER-/PR+ cases of invasive breast cancer. 

The researchers found that ER+/PR+ cancers showed a stronger association with alcohol than that seen in the overall group. Compared to non-drinkers, women who consumed less than one drink daily, one to two drinks, and three or more daily drinks, the increase in relative risk for developing ER+/PR+ breast cancer was 7 percent, 32 percent, and 51 percent, respectively. Although the data suggested increased risks among the women with ER+/PR- breast cancer, the number of cases was relatively small, and this finding was not statistically significant. The increased risk of invasive breast cancer was observed across different types of alcohol consumed. “Our study at this point provides evidence for the notion that alcohol affects estrogen metabolism, which increases risk of hormone sensitive breast cancer,” Lew said. “Still, more study is needed to clarify the effect of alcohol on other tumor types.” Association Between ADH1B and ADH1C Haplotype Tag SNPs and Breast Cancer Risk, and the Interaction with Alcohol Drinking: Abstract 5814

Specific variations within two genes involved with alcohol metabolism are associated with an increased risk for breast cancer in postmenopausal women, according to a new study. The work, conducted by research groups led by Peter Shields, M.D., professor of medicine and oncology at Georgetown University’s Lombardi Comprehensive Cancer Center and Jo Freudenheim, Ph.D., chair of social and preventive medicine at the State University of New York at Buffalo, indicates that sequence variations within the genes. ADH1B and ADH1C may as much as double a postmenopausal woman drinker’s risk for breast cancer. “We found that variations in two genes coding for the alcohol dehydrogenase enzyme increase the risk of breast cancer among women who drink,” said lead author Catalin Marian, M.D., Ph.D., a research instructor of cancer genetics and epidemiology at Georgetown. “The 
higher their alcohol consumption, the higher their risk.”

Marian and colleagues evaluated data from participants in the Western New York Exposure and Breast Cancer (WEB) Study, a population-based case-control study of breast cancer conducted by Freudenheim in women ages 35 to 79 from two western New York counties between 1996 and 2001. Women with primary, histologically confirmed breast cancer served as cases. Healthy control participants were randomly selected and matched to cases by age, race and county of residence. The research team analyzed DNA samples taken from 991 women with breast cancer and 1,698 controls. They found that variations within the DNA sequences rs1042026 in the gene ADH1B and rs1614972 in the gene ADH1C were associated with an increased breast cancer risk for postmenopausal women. Within the rs1042026 sequence, the risk of breast cancer for women who had a variant form of the gene and who drank alcohol was nearly twice that of women who abstained. The risk of breast cancer increased with the level of alcohol consumption.

Within the rs1614972 sequence, the variant form of the gene offered a protective effect against breast cancer that varied inversely proportional with the drinking level. The more alcohol women drank, the less protective the effect and the higher their risk of developing breast cancer. Marian cautions that the work needs to be explored further and replicated by other studies, as the research showed these sequence variations were associated with increased risk of breast cancer but were not necessarily biologically responsible for this effect. “These two genes encode for enzymes involved in the metabolization of alcohol, so variations in these genes can increase or decrease the rate of alcohol metabolism,” Marian said. “We have to keep in mind that the gene sequence variations we observed are not located directly 
in coding regions, but they may be associated and inherited together with other variations that have this effect on the enzyme function.”

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Breast Cancer Lymph Node Biopsy May Need Closer Look (HealthDay - 9/04/2008)


 A new long-term analysis of breast cancer patient survival suggests it might be time to update the way pathologists test lymph node biopsies. A team of New York City physicians found about one in four patients originally declared to be free of cancerous cells in their sentinel lymph nodes were actually not cancer-free, and that tiny cancer remnants called micrometastases reduced the women's survival over a 20-year 
period. These findings address a long-standing question among breast cancer researchers: Are such micrometastases prognostically significant? "This is the first study to show that there is a survival impact for the detection of micrometastases," said Dr. Stephen F. Sener, a professor of surgery at Northwestern University Feinberg School of Medicine in Chicago. The results are published in the April 10 issue of the Journal of Clinical Oncology. In the study, a team led by Dr. Hiram S. Cody III, a professor of clinical surgery at Memorial Sloan-Kettering Cancer Center in New York City, analyzed a population of 368 patients who were originally diagnosed with breast cancer in the 1970s. At the time, these patients were judged to be free of cancerous cells on the basis of a single tissue slice (standard procedure at that time). As a result of that diagnosis, these patients received no follow-up treatment for their disease.

Each of these patients was then monitored over the following 20 years or so. Cody and his team retrospectively reanalyzed the decades-old tissue samples using modern techniques. They then assessed how many of the slices did, in fact, contain cancerous cells, and whether those stray cancerous cells had affected the women's survival.  "What we found was that among these patients, 23 percent were converted to node-positive [cancer status], and among those who were converted, their survival was worse than among patients who remained node-negative," said Cody. "The 23 percent number is very significant, because it argues that if pathologists just do one section, you may want to ask them to do more," he explained. "We think the information you get by doing more is significant." According to Cody, 30 years ago the standard of care for breast cancer patients was complete dissection of the axillary lymph nodes (those found under the armpit) followed by cell-shape analysis using a single tissue slice from each node. Such a surgery would typically collect 15 to 20 nodes, on average. Today, however, a different, less traumatic approach called sentinel node biopsy is used. In sentinel lymph node (SLN) biopsy, a patient's tumor is injected with a combination of dye and radioactive tracer molecules. The following day, only those lymph nodes to which the tracer molecules migrated (the SLNs) are biopsied and analyzed. So, instead of harvesting 15 to 20 nodes, on average only two are three are collected using the new technique.

That reduction in work per node has a real payoff, because pathologists can delve much deeper into each sample, Cody explained. "Because you remove fewer nodes, you can study them more carefully, and we argue that the information you get by doing that is prognostically significant," he said. Current guidelines from the College of American Pathologists recommend analyzing one tissue slice per biopsied lymph node, Cody noted. Yet for years, he said, physicians have known that the more carefully one looks, the more cancerous cells one can find. The problem has always 
been one of balancing the additional work and expense required against the likelihood of success -- some studies have suggested a pathologist would need to analyze as many as 1,600 additional sections to find a single additional node-positive case. In the current study, Cody's team took four sections per node, analyzing two each for cell shape (morphology) and the presence of a molecular marker of cancer. Nine percent of patients were found to be node-positive using morphological criteria alone; the other 14 percent were detected using molecular markers. In both cases, survival was poorer than in patients who remained node-negative. "What we are suggesting is that perhaps the staging system for lymph node metastases should be reevaluated in the next edition of the AJCC [American Joint Committee on Cancer] 
staging," he said.


Many sites already analyze more than one slice per node, he added. Sener's facility, for instance, uses 10. According to Sener, the current findings underscore the need for additional systemic therapy, such as chemotherapy, in patients with SLN micrometastases. But he also noted that SLN micrometastases do not necessarily require surgical excision, as most patients with positive lymph nodes do not develop cancer under the arm. Sener hypothesized that could be because each metastasizing cancer cell has a sort of molecular ZIP code, which governs where it can go. Under this hypothesis, the decreased survivability associated with micrometastases has less to do with the lymph nodes per se, than with what those positive nodes say about metastases elsewhere in the body. "It may be that the presence of micrometastases in these lymph nodes may be a bystander phenomenon," Sener said, "a surrogate marker for the presence of the lung or liver ZIP code in these cells." Cody noted one "significant caveat" to this study: Because breast cancer survival and treatment regimens have changed so dramatically over the past 30 years, this study says nothing about the prognostic implication of micrometastases discovered today. That will require prospective studies, several of which are ongoing. Nevertheless, he said, "because we don't know the results of those studies yet, studies like our own may be the best available evidence at present, and our study suggests these micrometastases are prognostically significant."

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Chemotherapy-induced anemia increases risk of local breast cancer recurrence (Yahoo News)

Patients with breast cancer who developed anemia during chemotherapy had 
nearly three times the risk of local recurrence as those who did not, according to a study published in the April 1 issue of Clinical Cancer Research¸ a journal of the American Association for Cancer Research. “We speculate that there may be an interaction between chemotherapy/radiotherapy and anemia,” said lead researcher Peter Dubsky, MD, a senior consultant in the department of surgery at the Medical University of Vienna, Austria. “Both treatment modalities have been shown to be less effective in anemic patients. Since we do not see the effect in terms of relapse-free survival, the interaction with local adjuvant treatment may play a more important role.”
Dubsky and his colleagues from the Austrian Breast and Colorectal Cancer Study Group examined data from a randomized, clinical trial comparing adjuvant hormonal treatment and tamoxifen with the standard treatment of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). All women in the trial were premenopausal and had positive estrogen and/or progesterone receptor status. Patients who underwent breast-conserving surgery received mandatory radiation. Radiation was optional in women who underwent modified radical mastectomy.

For the current analysis, the researchers focused on anemia data from the 424 patients in the CMF arm, as the rates of anemia among those who received the hormonal treatment were low. They examined local relapse-free survival, relapse-free survival and overall survival. Anemia occurred in 18.2 percent of patients who received CMF chemotherapy. Anemia was defined as an incidence of at least one serum hemoglobin level below 12 g/dL during chemotherapy through the first follow-up date three months after adjuvant treatment concluded. After a median follow-up of 61 months, 39 local relapses occurred: 6.9 percent in patients without anemia and 19.5 percent in patients with anemia. The 5-year rates of relapse were 8.2 percent among nonanemic patients and 19.6 percent among anemic patients. Patients without anemia experienced a significantly longer local relapse-free survival than patients 
with anemia, according to the study. Other factors that significantly increased local relapse-free survival were younger age at diagnosis and negative lymph node status. Any relationship between anemia and tumor size, postoperative radiation or type of surgery did not have an effect on local relapse-free survival, researchers say. 

Relapse-free survival did not differ significantly with the presence or absence of anemia. “There seemed to be no difference when distant or contralateral events were part of the analysis,” said Dubsky. “The effect was limited to local recurrences. Any explanation of the limit is pure speculation.” No difference in overall survival was evident, but Dubsky says he doubted one would be seen given the number of patients and the length of follow-up. Follow-up of 10 to 15 years would be needed to observe any significant differences, he says.

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Breast Cancer More Aggressive Among Obese (Yahoo News)

Women with breast cancer have more aggressive disease and lower survival 
rates if they are overweight or obese, according to findings published in the March 15 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research. “The more obese a patient is, the more aggressive the disease,” said Massimo Cristofanilli, MD, associate professor of medicine in the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center. “We are learning that the fat tissue may increase inflammation that leads to more aggressive disease.” Cristofanilli and colleagues observed 606 women with locally advanced breast cancer. These women were classified by body mass index into the following three groups: normal/underweight (24.9 or below), overweight (at least 25 but less than 30) or obese (more than 30). Body mass index is calculated by dividing a person’s weight by their height. At five years, overall survival was 56.8 percent among obese women, 56.3 percent among overweight women and 67.4 percent among normal weight women. The 10-year survival rate was 42.7 percent among obese women, 41.8 percent among overweight women and 56.5 percent among normal weight women.

The rate of inflammatory breast cancer, previously shown to have worse outcomes than non-inflammatory breast cancer, among obese women was 45 percent compared with 30 percent in overweight women and only 15 percent in women considered normal weight, researchers found. Risk of breast cancer recurrence was also higher in obese or overweight women. By five years, 50.8 percent of obese women reported a recurrence compared with 38.5 percent of normal weight women. By 10 years, the rate of recurrence was 58 percent among obese women and 
45.4 percent among normal weight women. “Obesity goes far beyond just how a person looks or any physical strain from carrying around extra weight. Particular attention should be paid to our overweight patients,” Cristofanilli said.

Cristofanilli said physicians need to pay close attention to breast cancer patients because commonly used drugs, such as tamoxifen, tend to increase weight gain during treatment. “We have actually become quite good at managing acute side effects such as nausea in our chemotherapy patients and it goes away within a couple of days,” Cristofanilli said. “Following the nausea, our patients tend to overeat, which further increases their risk of weight gain. We need to impalement lifestyle modifications interventions and develop better methods to follow these patients closely.” The study was funded by the Susan G. Komen Foundation, the Nellie B. Connally Fund for Breast Cancer Research and the Inflammatory Breast Cancer Research Group.

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Hormones Can Raise Breast Cancer Risk (AP- 19/04/2008)

New Government Research Finds Menopause Hormones Can Raise the Risk of Breast Cancer. New government numbers give some of the strongest evidence yet that menopause hormones can raise the risk of breast cancer. Rates of the disease leveled off in 2004 after plunging in 2003, the year after millions of women stopped taking hormones because a big study tied them to higher heart, stroke and breast cancer risks. New U.S. government numbers showed that breast cancer rates leveled off in 2004 after plunging in 2003 the year after millions of women stopped taking hormones because a big study tied them to higher heart, stroke and breast cancer risks. Experts said the leveling off shows that the 2003 drop in the cancer rate was real and not a fluke.

From 2001 to 2004, breast cancer rates fell almost 9 percent a dramatic decline, researchers report in Thursday's New England Journal of Medicine. The trend was even stronger for the most common form of the disease tumors whose growth is fueled by hormones. Those rates fell almost 15 percent among women ages 50 to 69, the group most likely to have been on hormone pills. At the same time, a study of nearly 1 million women in the United Kingdom showed that those who took hormones after menopause were 20 percent more likely to develop ovarian cancer 
or die from it than women who never took the pills. That study was published online by the London-based journal The Lancet. For consumers, the new research doesn't change the advice to use the lowest dose for the shortest time possible for hot flashes and other menopause symptoms that can't otherwise be controlled.

For cautious scientists, the new breast cancer numbers were more evidence of the 
hormone-breast cancer link. "The story has gotten stronger," said Dr. Peter Ravdin, a biostatistician at the University of Texas M.D. Anderson Cancer Center in Houston who led the research. Some were skeptical several months ago when Ravdin and National Cancer Institute researchers first reported the 2003 drop in the breast cancer rate. The new numbers, which add 2004, prove this was no fluke, said Dr. Julie Gralow, a spokeswoman for the American Society of Clinical Oncology and cancer expert at the University of Washington in Seattle. Because it didn't bump back up again," it supports the idea that the rate has stabilized at a new lower level, said Gralow, who had no role in the study.

Brenda Edwards, one of the journal authors who is a National Cancer Institute researcher, agreed. "Now we have a statistically significant decline" over three years and clear proof of a trend, she said. Although some recent analyses suggest heart risks from menopause hormones are not as great as had been believed for younger, newly menopausal women, the statistics out this week add to the worries about cancer. After rising steadily through the 1990s, the breast cancer rate dipped from 2001 to 2002, from 138 cases to 135 cases per 100,000 women. After the federal Women's Health Initiative study reported in July 2002 on the health risks of hormones, use of the pills plunged. So did the breast cancer rate the following year to 126 cases per 100,000 women. It was the steepest fall since the government started keeping records in the 1970s.

The drop was seen in all of the cancer statistics registries reviewed in the study, and no other cancer rate changed as dramatically strong signs that hormones were playing a role, specialists said. The 2004 rate held steady at about 126 cases per 100,000. Stopping hormone use may have stopped some cancers from growing and caused them to disappear, scientists speculate. Or it may have just slowed them down so that they won't appear until years later, said Ahmedin Jemal, an American Cancer Society researcher. Only time will tell which is true, he said. Wyeth Pharmaceuticals, which makes top-selling hormone pills Prempro and Premarin, criticized the study as overly speculative. Company spokesman Dr. Joseph Camardo said hormone prescriptions continued to fall in 2004 but breast cancer rates did not decline proportionately. Ravdin said the company's criticism does not invalidate the cancer trends. Breast cancer is the most common major cancer in American women and the second leading cause of cancer deaths in women. About 180,000 new cases are expected to occur in the United States this year and more than 1 million worldwide.

Ovarian cancer is far less common. The British study found that even with the 20 percent greater risk from hormones, the actual risk was very low: 2.6 of every 1,000 hormone users developed ovarian cancer over five years compared to 2.2 in 1,000 non-hormone users. Hormone use has declined already, and the new report should cause it to fall further, Dr. Steven Narod of the University of Toronto wrote in an editorial accompanying the study in The Lancet. "We hope that the number of women dying of ovarian cancer will decline as well," he wrote. Camardo, Wyeth's spokesman, said hormone labels already warn about an elevated risk of 
ovarian cancer.

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Can we please stop the mandated lying to women now? (Yahoo News- 24/04/2007)


A Harvard University research study just out confirms what the National Cancer Institute said in 2003:
There is no link between abortion and breast cancer. There is no link between miscarriage and breast cancer. The Harvard study followed more than 100 thousand women for ten years (part of the huge Nurses Health Study that has yielded so much info about women's health). It's merely one more study that comes to the same conclusion, one which is held by the American Cancer Society, as well. As the vice president for epidemiology and surveillance research at the American Cancer 
Society, Dr. Michael Thun said:
"There is no evidence that having had an abortion increases the risk of breast cancer. This is a subject that has received a lot of visibility; something that has been looked at repeatedly. There is strong scientific consensus this is the case." Ah, yes, scientific consensus, but of course, not political consensus. 

The Coalition on Breast Cancer/Abortion immediately rejected this study, like all the previous ones, as flawed. They describe the 2003 finding by the world's top cancer experts that there is no linkage between abortion and breast cancer "a political sham." The politicization of women's health has been unstoppable for the last six years. Four states require doctors to tell women about a potential link to breast cancer as part of pre-abortion counseling, and similar efforts to legislate through phony scare tactics are under way in other states as well. What's it going to take for states to stop mandating that doctors lie to their patients? Those of us who have taken our rights for granted since Roe v. Wade got a huge wake up call from the Supreme Court last week. But the alarm has been ringing for years.

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Couples to test embryos for cancer gene (UPI - 27/04/2008)

Two British couples want to use an embryo selection technique to eradicate a breast cancer gene that runs in their families. Scientists say screening for the defective BCRA1 gene would reduce the likelihood of cancer, The (London) Guardian reported Friday. The London Times said an application to test for the breast cancer gene was submitted Thursday by a doctor at University College Hospital. The newspaper said Britain's Human Fertilization and Embryology Authority has already agreed to it in principle. The application is expected to be approved within four months. The couples will have in vitro fertilization, and a single cell will be removed from the embryos at the eight-cell stage and tested for the BRCA1 gene. Only unaffected embryos would be transferred to the women's wombs, The Guardian said.

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Tamoxifen Protects Certain Women at High Risk for Breast Cancer (HealthDay News - 2/5/2007)

Tamoxifen helps prevent breast cancer in women at high risk for the disease who have also had their ovaries removed as part of a hysterectomy, researchers report. The new study, "reaffirms that tamoxifen is still a tremendous drug for prevention of breast cancer in women who are at a high risk for development of the disease," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. He was not involved in the trial. The study -- an extended follow-up of the Italian Randomized Tamoxifen Trial -- is published in the May 2 issue of theJournal of the National Cancer Institute. The initial findings of the trial found tamoxifen offered no reduction in women's risk for breast cancer. Nor had some other European trials, some of which looked at women with different risk profiles.

But an earlier and much larger study, the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial, had shown that tamoxifen could cut the risk of estrogen-receptor-positive breast cancer -- tumors that grow in the presence of estrogen. In fact, that trial was halted early, because the risk reduction in invasive breast cancer was so striking. Here, the authors presented 11-year follow-up data on more than 5,400 women who had undergone a hysterectomy (including having both ovaries removed) and who had been randomly assigned to receive tamoxifen or a placebo for five years. Ovaries make estrogen, so removing them ensures that no extra estrogen -- which can fuel some breast cancer tumors -- is being produced. For women at low risk for breast cancer, disease rates were similar whether or not they took tamoxifen, the researchers reported. The situation was different for higher-risk women. In that case, women taking tamoxifen had lower rates of hormone-receptor-positive breast cancer than those taking a placebo: 1.5 per 1,000 women-years in the tamoxifen group versus 6.26 per 1,000 women-years in the placebo group. There was also a greater reduction in risk for tumors that were both progesterone- and estrogen-receptor positive, than for tumors which were estrogen-receptor positive and progesterone-receptor negative.

Women in the tamoxifen group also had more side effects, including hot flashes and heart problems. These are noted side effects of the drug. A woman's cardiac risk needs to be assessed before she is started on tamoxifen, the authors stated. The new study "reaffirms the pioneering work that the NSABP did back in the '90s," Brooks said. "Tamoxifen is still an excellent drug for prevention of breast cancer and is underutilized," he added. Another expert said newer drugs can help, too. "Tamoxifen does decrease the risk of invasive breast cancer," said Dr. Alison Estabrook, chief of breast surgery at St. Luke's-Roosevelt Hospital in New York City. "We're hoping that the new aromatase inhibitors which are being tried now for prevention will reduce the risk of breast cancer, which they should." Aromatase inhibitors, which lower the amount of estrogen in the body by blocking a key enzyme, have far fewer side effects than tamoxifen. Another drug, raloxifene, also has fewer side effects but does not prevent noninvasive breast cancer, whereas tamoxifen works on both, Brooks said.

In other findings, reported in the same issue of the journal, a team at Baylor College of Medicine in Houston used a three-drug combo to block the growth of aggressive breast cancers in mice. The team added two cancer drugs, gefitinib and pertuzumab, to Herceptin (trastuzumab) to help slow the growth of tumors with higher levels of a protein called HER-2. Herceptin was designed to block HER-2 but proved much more effective with the addition of the other two agents, the researchers found. A clinical trial will begin soon, said co-investigator Dr. Kent Osborne, director of the Breast Center and Dan L. Duncan Cancer Center at Baylor. "We are very excited to see if our laboratory results can be translated to patients with the more aggressive types of breast cancer," he said in a statement.

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Ovarian Drugs to Treat Breast Cancer? (Yahoo News- 18/05/2007)


Drugs that affect the ovaries may help treat some women with hormone-sensitive breast cancer, researchers report in The Lancet. They included Jack Cuzick, PhD, who works in London at Cancer Research U.K. Cuzick and colleagues focused on a class of drugs called LHRH agonists, which can reduce the amount of estrogen produced by the ovaries. Examples of LHRH agonists include Zoladex and Lupron. About two-thirds of women with breast cancer have estrogen-sensitive breast tumors, meaning that those tumors are fueled by estrogen. Curbing estrogen helps fight those cancers. Breast cancer drugs that target estrogen include tamoxifen and aromatase inhibitors. Those drugs work differently from LHRH agonists. Cuzick's team pooled data from 16 studies of about 11,900 premenopausal women with hormone-sensitive breast cancer. Relatively few women only took LHRH agonists. Others just got chemotherapy and/or tamoxifen. Still others got LHRH agonists in addition to chemotherapy and/or tamoxifen.

Study's Results

Cuzick's team found that LHRH agonists, taken alone, were comparable to chemotherapy in reducing the odds of breast cancer recurrence or death from breast cancer recurrence. Adding LHRH agonists to chemotherapy and/or tamoxifen lowered recurrence by nearly 13 percent and lowered death after recurrence by about 15 percent. Those effects were strongest in women less than 40 years old. However, it's too soon to recommend the addition of LHRH agonists for all premenopausal women with hormone-sensitive breast cancer, according to an editorial published in The Lancet. "In women with higher-risk disease, chemotherapy followed by tamoxifen should still be the standard approach, with the addition of an LHRH analogue [agonist] a reasonable consideration for those who remain premenopausal," write the editorialists. They included Nicholas Wilcken, MBBS, PhD, FRACP, who works in Sydney, Australia, in the medical oncology department of Westmead and Nepean Hospitals and the University of Sydney. The Lancet notes that Cuzick is a statistical consultant for the drug company AstraZeneca, which makes Zoladex, but that work is unrelated to the drugs in this study.

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Researchers find big batch of breast cancer genes -(Reuters- 28/05/2007) 


A genetic mutation that raises the risk of breast cancer is found in up to 60 percent of U.S. women, making it the first truly common breast cancer susceptibility gene, researchers report. Reports from several teams around the world identified changes in four other genes that raise the risk of breast cancer significantly. Several are found in many men and women. More than 60 percent of the women in the United States probably carry at least one of the mutations in one of the genes, called FGFR2, the researchers said. "This is a truly landmark breakthrough for breast cancer research, because these genes are the first confirmed common genetic risk factors for breast cancer," said Jianjun Liu of the Genome Institute of Singapore, who took part in one of the studies. The researchers, reporting in the journals Nature and Nature Genetics, said the discoveries are the most important genes associated with breast cancer since BRCA1 and BRCA2 were identified. Women with faulty copies of BRCA1 or BRCA2 have a 50 percent to 85 percent chance of getting breast cancer in their lifetimes. But they are rare genes, and account for only 5 percent to possibly 10 percent of breast cancer cases. Researchers have been testing women for other genes associated with breast cancer, to find its causes, to understand how and why it develops, and to make more effective treatments. Better techniques to analyze DNA, and the publication of the human genome, the map of all DNA in the body, have made this a much faster and easier process. David Hunter of Harvard University and a team at the U.S. National Cancer Institute looked at more than 2,200 women of European ancestry. Common gene, big risk. They found four common mutations in FGFR2 associated with the breast cancer in women after menopause who do not have known relatives with breast cancer.

The mutations raise the risk of breast cancer risk by 20 percent if they carry one 
copy of the gene and by 60 percent if they carry two copies. And close to 60 percent 
of the women they studied carried at least one copy. The findings do not yet have any real relevance for women, Hunter stressed. "It is premature to recommend screening women for these gene variants, at least until the scientific community has further combed through the genome-wide findings and found all the variants that are associated with increased risk," Hunter said in a statement. Douglas Easton of Britain's University of Cambridge led a team of researchers around the world to look at tiny changes in the DNA code called single nucleotide polymorphisms or SNPs -- pronounced "snips" -- in the DNA of 21,860 people with breast cancer and 22,578 people without it. They found mutations in four genes that were more common in the people with breast cancer -- FGFR2, TNRC9, MAP3K1 and LSP1. FGFR2 may be a logical candidate for a breast cancer gene -- it is a receptor, a kind of molecular doorway, for compound called tyrosine kinase which is involved in several cancers. In a third study, a team at deCODE genetics, the University of Nijmegen in the Netherlands and elsewhere studied 22,000 people to find two other gene mutations associated with breast cancer. One is also near TNRC9. "DeCODE estimates that these two variants are contributing factors in one quarter of breast cancer cases in women of European origin," the company wrote in a statement. Breast cancer kills 500,000 people a year globally according to the World Health Organization, and 1.2 million men and women are diagnosed with it every year.

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The recent drop in the rate of the cancer is tied to a sharp decrease in hormone replacement therapy, records indicate. -( Los Angeles Times- 24/07/2007) 



Patient treatment records from a large HMO show that the recent decline in breast 
cancer rates is linked to a sharp drop in use of hormone replacement therapy and not 
to declines in mammography, as many researchers had speculated, researchers said Monday. Dr. Andrew G. Glass and his colleagues at Kaiser Permanente Northwest in Portland, Ore., found a drop in breast cancer rates among their patients from 2003 to 2006 even though mammography rates remained virtually constant, they reported in the Journal of the National Cancer Institute. A lowered mammography rate means fewer breast cancers are detected. Researchers are not sure why that rate declined. By using a patient population for whom the mammography rate remained constant, "we were able to disentangle mammography from hormones," Glass said. 
In an editorial in the same journal, Dr. Donald A. Berry and Dr. Peter M. Ravdin of the University of Texas M.D. Anderson Cancer Center in Houston agreed that declines in 
mammography could not be responsible for the bulk of the decline in breast cancer. 
"The only known factor that would seem to explain the precipitous drop in incidence is 
the sharp decrease in use of menopausal hormone therapy," they wrote. No one is suggesting that estrogen triggers the formation of breast tumors. Rather, most researchers think that it accelerates the growth of existing tumors. Stopping hormone replacement therapy slows the growth of small tumors, delaying their detection and producing an apparent decline in incidence, Berry and Ravdin speculated. Prescriptions for estrogen and progestin fell by nearly half in 2003 after 2002 results from the Women's Health Initiative linked an increased breast cancer risk to hormone replacement therapy.

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Researchers Identify Gene Involved In Breast Cancer -( AP Medical Writer- 28/07/2007) 



Researchers at the University of Michigan Comprehensive Cancer Center have identified a gene linked to the development of an aggressive form of breast cancer. The researchers found that the gene, FOXP3, suppresses tumor growth. FOXP3 is located on the X chromosome, which means a single mutation can effectively silence the gene. This is unusual, as only one other gene linked to cancer has been found on the X chromosome. When one copy of the FOXP3 gene is silenced, the researchers found in studying mice, 90 percent of the mice spontaneously developed cancerous tumors. The researchers also looked at FOXP3 in human breast tissue cells, comparing cancerous and non-cancerous cells. FOXP3 was found to be either deleted or mutated in a substantial portion of the cancer sample: about 80 percent of the cancer tissues studied did not express the gene at all. In addition, the researchers found FOXP3 to be a repressor of HER-2, a protein that typically marks a more aggressive form of breast cancer. The researchers believe FOXP3 suppresses the HER-2 gene. HER-2 can be activated by many different factors, but the researchers found that when FOXP3 is normal, it keeps HER-2 levels low; when FOXP3 is missing or mutated, HER-2 levels are likely to rise. The researchers have shown that FOXP3 was reduced or missing in about 80 percent of the more than 600 cases of breast cancer tissue examined. At this point, the researchers do not know if FOXP3 can predict breast cancer risk, like the BRCA1 and BRCA2 genes, both of which are linked to a higher risk of breast cancer. "FOXP3 defects promote cancer development. We do not know whether this is a genetic defect that puts women at higher risk. For treatment, this gene could be quite important, but for diagnosis, it's too early to tell," says study author Yang Liu, Ph.D., deNancrede Professor of Surgery at the U-M Medical School and co-director of the cancer immunology program at the U-M Comprehensive Cancer Center. Results of the study appear in the journal Cell. Initially, the researchers were studying FOXP3's role in autoimmune disease, when they noticed that female mice with one copy of the mutated form of the gene were developing breast cancer. Moreover, the tumors expressed high levels of ErbB2, the mouse equivalent of HER-2. Breast cancer is rare in mice, and ErbB2-positive breast cancer is even more rare.

"FOXP3 is the first X chromosome-linked gene that suppresses breast cancer and 
represses the HER-2/ErbB2 oncogene. Given the significant role HER-2 plays in breast cancer and the widespread defects we found on FOXP3, it is likely that this gene play an important role in suppressing breast cancer," says Pan Zheng, M.D., Ph.D., associate professor of surgery and pathology at the U-M Medical School. The research is still in early stages. No predictive or diagnostic test is available involving this gene finding. More than 180,000 women will be diagnosed with breast cancer this year, and 40,900 will die from the disease, according to the American Cancer Society. In addition to Zheng and Liu, U-M study authors were Lizhong Wang, Xing Chang, Huiming Zhang, Weiquan Li, Yan Liu, Yin Wang, Bae Keun Park and Cun-Yu Wang. Additional authors are Tao Zuo, Carl Morrison, Michael W.Y. Chan, Jin-Qing Liu, Chang-gone Liu, Rulong Shen, Xingluo Liu, Tiany Yang, Tim H.-M. Huang, and Richard Love from Ohio State University; and Virginia Godfrey from the University of North Carolina, Chapel Hill. Funding for the study was from the National Institutes of Health and U.S. Department of Defense. The University of Michigan has filed a patent application on this research technology, and is currently looking for a corporate partner to help bring the technology to market.

Reference: Cell, Vol. 129, issue 7, pp. 1275-1286

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