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Breast Cancer Risk Factors

by Hans R. Larsen, MSc ChE

Vitamin D and breast cancer
Hans Larsen SAN DIEGO, CA. A report has just appeared in the Journal of Steroid Biochemistry & Molecular Biology by Garland et al that addresses the issue of vitamin D and breast cancer risk with a pooled analysis of studies that determined the vitamin D status from serum 25-hydroxyvitamin D (25(OH)D) levels. The list of authors includes both well-known vitamin D experts and nutritional epidemiologists. The authors were only able to find two studies that met their requirements for inclusion in their pooled analysis, but together they involved 1760 individuals. Both studies covered a wide range of 25(OH)D levels and exhibited a high level of inverse correlation between breast cancer risk and the serum level of this vitamin D marker. When pooled analysis was carried out, the odds ratios for the lowest to highest quintile of 25(OH)D levels were 1.00, 0.90, 0.70, 0.70 and 0.50, i.e. the highest vitamin D status provided a 50% reduction in risk. The authors present a graph of risk (odds ratio) against serum 25(OH)D levels with an amazing correlation coefficient of 0.94 (a statistical measure of the goodness of fit to the model, in this case a straight line, and 1.00 represents a perfect fit), a correlation coefficient that would please those trained in the physical sciences and in fact a correlation very rarely seen in plots presented in the medical literature.

The authors discuss the level of intake that would accomplish the 50% level of risk reduction. If a person were to start at a serum level of 24 nmol/L (10 ng/mL) it would require supplementation of 4000 IU/day to achieve the required level of 120 nmol/L. This exceeds the current upper limit of 2000 IU/day. However, as they point out, a proposal has been made to raise this limit to 4000 IU/day. Levels of 24 nmol/L are not uncommon among US women in the winter months. An alternative they explore is to take 2000 IU/day orally and make up the balance by judicious sun exposure. They estimate that 12 minutes of sun exposure for 50% of the skin would produce the missing 2000 IU. However, this would not happen in the northern latitudes in the winter months. The authors hammer home their point regarding the importance of vitamin D by calculating that, based on their data, an intake of 4000 IU of vitamin D per day would, in the U.S., prevent over 100,000 cases of breast cancer per year. Intake of 2000 IU/day was estimated to prevent 66,000 cases. In this paper, vitamin D refers to vitamin D3.
Garland, C. F. et al. Vitamin D and the Prevention of Breast Cancer; Pooled Analysis. Journal of Steroid Biochemistry & Molecular Biology, 2007, Vol. 103, pp. 708-711.

Weight gain and breast cancer risk
NEW YORK, NY. Over the years there has accumulated considerable evidence concerning the association between indicators of body size and postmenopausal breast cancer. However, little is known about the importance of the timing of weight gain in adult life. This issue has recently been addressed in a large international population-based case control study. Included were 1166 cases of primary histologically confirmed postmenopausal breast cancer and 2105 controls matched on age, race and country of residence. Data on weight gain and fat distribution were collected through in-person interviews and questionnaires. Participants were asked to recall their body weight for each decade from age 20 to one year before diagnosis for cases and to 1 year before interview for controls. Information was also collected on weight gain during first pregnancy and body shape at menarche. Current height, weight and measures of central adiposity (abdominal fat collection) and hip and waist circumferences were also noted. For the cases, the estrogen and progesterone status of the breast cancer was obtained from pathology reports.

For lifetime adult weight gain it was found that there was a 4% increase in risk of postmenopausal breast cancer for each 5 kg (11 lbs) increase in adult weight, In addition, there was a tendency for a stronger association for those with a higher waist circumference which suggested that fat accumulation around the waist was of greatest significance. Only those with estrogen/progesterone positive tumors exhibited weight-related increases in risk. Weight gain from age of first pregnancy to assessment was also associated with increased risk, but the trend with the amount of weight gain was not significant. However, weight change from age of first pregnancy to age of menopause was associated with increased risk with a significant trend associated with the amount of weight gain. Other than this, there were no significant associations with the time of life in which weight gain occurred. This study also confirmed what others have observed, i.e. there is a protective effect of higher body weight at age 20, with women in the highest quartile having a significant reduced risk of 27% as compared to those in the lowest quartile. No association was found for weight gain during pregnancy and the risk of postmenopausal breast cancer.
Han, D. et al. Lifetime Adult Weight Gain, Central Adiposity, and the Risk of Pre- and Postmenopausal breast cancer in the Western New York Exposures and Breast Cancer Study. International Journal of Cancer, 2006, Vol 119, pp. 2931-37

Weight gain during adulthood increases breast cancer risk
ATLANTA, GEORGIA. Breast cancer in postmenopausal women has previously been linked to carrying excess weight. However, questions remain over the links between weight gain and breast cancer, and the specific types of breast cancer which may be involved. Researchers from the American Cancer Society set out to answer these questions by analyzing data from a group of 44,161 postmenopausal women enrolled in the society's Cancer Prevention Study II Nutrition Cohort. The women, none of whom were on hormone therapy, were divided into categories by weight gain since the age of 18. Of the women, 1,200 had been diagnosed with invasive breast cancer.

Overall, the women who gained weight in adulthood faced a higher lifetime risk of all types of breast cancer after menopause. The greater the amount of weight gained, the greater the risk of breast cancer of all types, stages, and grades. Specifically, women who gained over 60 pounds had an 89 per cent higher risk of ductal type tumors than women who gained 20 pounds or less during adulthood, and 54 per cent higher risk of lobular type cancers. The likelihood of metastatic disease (cancer which spreads to other organs) was more than three times higher among women who gained over 60 pounds. When hormone receptors in the breast cancer cells were examined, it was found that weight gain was linked exclusively to tumors with estrogen receptors present (ER-positive). This is predicted by earlier findings that breast cancer risk is linked to increased lifetime levels of circulating estrogen. Fat tissue increases estrogen levels, contributing to the risk. Obese women may have the chance of mitigating their breast cancer risk by taking hormone replacement therapy, the researchers explain. They add that current weight is not as important as weight gained since the age of 18. These data underline the importance of maintaining a healthy body weight throughout adulthood, they conclude.
Feigelson, H. S. et al. Adult Weight Gain and Histopathologic Characteristics of Breast Cancer among Postmenopausal Women. Cancer, published online May 22, 2006.

Vitamin D, breast and ovarian cancer
LONDON, UK. Exposure to solar ultraviolet B radiation (UVB) has been found to correlate with age-adjusted incidence of ovarian cancer in a study involving 175 countries and based on data from 2002. Not only was an inverse relationship found, but when the correlation with stratospheric ozone, which reduces UBV, was examined, a positive association was found consistent. These results are consistent with earlier studies that found a north-south gradient for age-adjusted mortality rates for ovarian cancer. In another recent study, serum levels of the vitamin D metabolite, 25-hydroxyvitamin D, were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 of which had early stage cancer and 75 of which had locally advanced or metastatic disease. Patients with early stage disease had significantly higher circulating levels of 25-hydroxyvitamin D than those with advanced disease. The authors suggest that these results lend weight to the hypothesis that the growth of breast cancer in vivo is inhibited by vitamin D.
Garland, C.F. et al. Role of Ultraviolet B Irradiance and Vitamin D in Prevention of Ovarian Cancer. American Journal of Preventive Medicine., 2006y, Vol 31, No. 6,pp. 512-14. Palmieri, C. Serum 25-Hydroxyvitamin D Levels in Early and Advanced Breast Cancer. Journal of Clinical Pathology, 2006, published on line ahead of print.

Breast cancer risk from magnetic fields investigated
SEATTLE, WASHINGTON. The possibility that magnetic fields may increase the risk of breast cancer has recently been investigated by scientists at the Fred Hutchinson Cancer Research Center. They suggest that exposure to magnetic fields may interfere with the usual rise in melatonin levels at night. Melatonin is a hormone that is secreted by the pineal gland in the brain in response to darkness, and is important for the regulation of circadian rhythms. As melatonin is thought to be an oncostatic agent (i.e. a deficit can lead to an increased risk of cancer), the researchers speculate that disruption to melatonin production could raise breast cancer risk either by direct oncostatic action, or by increasing circulating levels of reproductive hormones related to the development of breast cancer. Support for their theory comes from animal studies, which show that exposure to magnetic fields can disrupt the nocturnal release of melatonin. They examined whether exposure to a 60-Hz magnetic field was associated with a decrease in melatonin among 115 women ages 20 to 40 years, as measured by levels of 6-sulfatoxymelatonin in the urine at night. They also measured levels of the reproductive hormones luteinizing hormone, follicle-stimulating hormone, and estrogen. The women were exposed to 60Hz magnetic fields 5 to 10mG (milligauss) above normal background levels for five consecutive nights, after which a nighttime urine sample was taken. Magnetic field exposure was linked to decreased melatonin levels, but not to a significant degree until certain participants were excluded (on grounds of eligibility). No changes in the reproductive hormones were found. However, the authors propose there may be subgroups of individuals who are more susceptible to the effects of magnetic field exposure on hormone levels, such as obese women, those on certain medications, and women during a menstrual cycle in which they do not ovulate. The authors conclude that, on the basis of this study, any breast cancer risk posed by magnetic fields through lowered melatonin levels does not occur via corresponding changes in reproductive hormones.
Davis, S. et al. Effects of 60-Hz Magnetic Field Exposure on Nocturnal 6-Sulfatoxymelatonin, Estrogens, Luteinizing Hormone, and Follicle-stimulating Hormone in Healthy Reproductive-age Women: Results of a Crossover Trial. Annals of Epidemiology, published online February 2, 2006

Breast cancer linked to depression
TEHRAN, IRAN. Many women believe that stress and depression increase the risk of breast cancer. Iranian researchers have now confirmed this belief. Their study involved 3000 women attending a breast cancer screening clinic in Tehran during the period 1997-1999. Data were collected regarding age, education, marital status, age at first menstruation, age at first full-term pregnancy, family history of breast cancer, menopausal status, oral contraceptive use, presence of depression and anxiety, and overall health. A diagnosis of breast cancer was made for 243 patients. The data for these patients were combined with that from 486 cancer-free controls and analyzed.

The researchers confirmed that early age at first menstruation (menarche) and a family history of breast cancer are potent risk factors for breast cancer. However, they also found a strong association between depression, anxiety, a feeling of hopelessness, and loss of interest and pleasures and the risk of breast cancer. Women who were depressed and hopeless had almost twice the risk of developing breast cancer than did more cheerful and upbeat women even after allowing for other known risk factors.
Montazeri, A, et al. The role of depression in the development of breast cancer: analysis of registry data from a single institute. Asian Pacific Journal of Cancer Prevention, Vol. 5, No. 3, July-Sept. 2004, pp. 316-19

Breast cancer linked to stress
SZCZECIN, POLAND. Polish researchers report that psychological stress is a powerful risk factor for the development of breast cancer. Their study involved 257 women who had undergone breast cancer surgery during the period 1993-1998 and 565 controls who were free of breast cancer. The participants were questioned in detail about their diet, lifestyle, and reproductive history and also reported exposure to major stressful life events, stress of daily activity, and work-related stress. After adjusting for age and other known risk factors, the researchers concluded that women whose daily life was stressful, who had experienced major stressful life events (divorce, loss of spouse, etc) and suffered from depression had a 3.7 times higher risk for breast cancer than did women who did not experience such stress. Work-related stress, on its own, was associated with a statistically non-significant increase in breast cancer risk of 16%.
Kruk, J and Aboul-Enein, HY. Psychological stress and the risk of breast cancer: a case-control study. Cancer Detection and Prevention, Vol. 28, No. 6, 2004, pp. 399-408

Breast cancer linked to use of antibiotics
SEATTLE, WASHINGTON. Antibiotics are effective in treating bacterial infections, but have no effects on viral and other non-bacterial infections. Yet, in 1995 over 22 million prescriptions for antibiotics were issued for non-bacterial, acute respiratory infections in the United States alone. It is clear that antibiotics are being vastly over prescribed and this makes the possibility of an association between breast cancer and antibiotics use of even greater concern.

Researchers from the University of Washington and the Fred Hutchinson Cancer Research Center recently reported a clear association between the risk of breast cancer and exposure to antibiotics. Their study involved 2266 women with primary, invasive breast cancer and 7953 randomly selected age- matched controls. The researchers found that women who had been exposed to antibiotics for 1-50 days had a 45% greater relative risk of developing breast cancer and dying from breast cancer than did women who had never used antibiotics. Women who had used antibiotics for more than 1,000 days in their lifetime had double the risk.

The researchers point out that it is not clear whether the observed association is due to the fact that antibiotics actually promote breast cancer or whether the increased risk stems from the underlying condition (infection, inflammation) that is being treated with the antibiotic. Antibiotics are known to disturb the intestinal microflora and interfere with the metabolism of phytochemicals that may help prevent cancer. The antibiotic tetracycline may be associated with an increased production of inflammatory prostaglandins. The researchers found no difference in association between breast cancer and antibiotic- use among premenopausal versus postmenopausal women and the type of antibiotic used did not alter the strength of the association either. They conclude that their findings lend further support to oft- repeated warnings to limit the prescription of antibiotics as much as possible and not prescribe them for non-bacterial infections.
Velicer, CM, et al. Antibiotic use in relation to the risk of breast cancer. Journal of the American Medical Association, Vol. 291, February 18, 2004, pp. 827-35
Ness, RB and Cauley, JA. Antibiotics and breast cancer - what's the meaning of this? Journal of the American Medical Association, Vol. 291, February 18, 2004, pp. 827-35

Editor's comment: It seems to me that the observed association could well involve candida overgrowth. Frequent and prolonged use of antibiotics will almost certainly lead to an overgrowth of candida (yeast infection). Candida, like alcohol, is a potent generator of aldehyde and both alcohol itself and its metabolite, acetaldehyde, have been linked to an increased risk of breast cancer. I have seen no medical evidence of a possible candida connection, but to be on the safe side it is a good idea to take probiotics (acidophilus) when taking antibiotics unless there is a specific reason not to.

Electric blankets linked to breast cancer.
A study involving 304 African-American women diagnosed with breast cancer and 305 matched controls concludes that the use of an electric blanket or mattress pad is associated with a 50% increase in the risk of breast cancer. The risk increases the more often the heating device is used and with the number of years it is used. Women who used it more than one of the 4 seasons had a 4-fold increase in risk and those who used it for 10 years or more had a 6-fold risk increase. Risk was substantially reduced it the heating device was only used to warm the bed and was then turned off. Overall risk was higher in premenopausal women than in post menopausal women.
American Journal of Epidemiology, Vol. 158, October 15, 2003, pp. 798-806

Cancer trends in the USA
ATLANTA, GEORGIA. The annual report on the status of cancer in the United States has just been released. The report is a joint effort of the American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries. Overall cancer incidence rates were essentially stable between 1995 and 2000, but may be increasing slightly if allowing for reporting delays. Overall cancer death rates have remained steady from 1998 to 2000. More than half of all cancer diagnoses and deaths involve lung cancer, breast cancer, prostate cancer or colorectal cancer (cancer of the colon or rectum).

Lung cancer
Lung cancer incidence and mortality have been declining among men since 1991, but have increased among women. This is no doubt due to the fact that smoking control programs have been far more effective among men than among women. The average annual death rate from lung cancer was 56.8 per 100,000 for men and 40.7 for women (1996-2000). Lung cancer rates were lowest in Utah, the state with the lowest adult prevalence of smoking (13%) and the highest in Kentucky, the state with the highest adult smoking prevalence (31%).

Breast cancer
The incidence of female breast cancer has increased continually since 1986 particularly among white women. Death rates, however, have decreased steadily since the early 1990s possibly due to the more extensive use of mammography screenings. The average annual death rate from breast cancer (1996- 2000) was 27.7/100,000 with slightly higher rates observed among black women.

Prostate cancer
The incidence of prostate cancer has increased by 2.3% per year since 1994 and more recently by 3.0% per year among white men and by 2.3% per year among black men. Death rates, on the other hand, have been steadily declining and now stand at 32.9/100,000 (30.2 among white men and 73.0 among black men). Some experts argue that the increased use of PSA testing is responsible for the decline in mortality; however, the subject of screening for cancers is a highly controversial one. Dr. M.J. Quinn of the UK National Cancer Intelligence Centre points out that the use of the prostate specific antigen (PSA) test for screening purposes is not recommended by the US Preventive Services Task Force or in the European Code Against Cancer. He is clearly opposed to the use of PSA testing for screening purposes and points out that it may lead to unnecessary biopsies and dangerous treatments without any proven reduction in mortality.

Cancer of the colon and rectum
The incidence of colorectal cancer has stabilized since 1995 for both men and women and death rates have declined. Overall mortality rate for the period 1996-2000 was 21.2 per 100,000, but was particularly high among black men at 34.6/100,000.

The report concludes that overall cancer incidence and death rates began to stabilize in the mid to late 1990s, but have lately shown signs of increasing again.
Weir, Hannah K, et al. Annual report to the nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control. Journal of the National Cancer Institute, Vol. 95, September 3, 2003, pp. 1276-99 Quinn, MJ. Cancer trends in the United States - A view from Europe. Journal of the National Cancer Institute, Vol. 95, September 3, 2003, pp. 1258-61

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No benefits of hormone therapy
SAN FRANCISCO, CALIFORNIA. In 1995 researchers at the Harvard Medical School reported that estrogen or combined estrogen/progestin therapy increased the risk of breast cancer in postmenopausal women. The fact that unopposed estrogen therapy increases the risk of breast cancer had been reported in 1992. Shortly thereafter a large clinical trial was begun to see if estrogen/progestin therapy (HRT) would be of benefit to postmenopausal women with heart disease. This trial, the Heart and Estrogen/Progestin Replacement Study (HERS), involved 2763 postmenopausal women with documented coronary heart disease. Half the participants (1380 women) were assigned to receive 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate daily; the other half (1382 women) received a placebo. After 4.1 years of follow-up there was no indication that HRT was of any overall benefit in preventing non-fatal heart attacks or death from heart disease. It did appear that HRT users had more cardiac events than the placebo users in the first year, but this was compensated for by fewer events in years three to five. The HERS study was continued in a slightly modified form (HERS II) for another 2.7 years. At the end of the total 6.8 years of follow-up the conclusions were:

  • HRT does not reduce the risk of cardiovascular events in postmenopausal women with heart disease;
  • HRT doubles the risk of blood clots (venous thromboembolism);
  • HRT increases the risk of gallstones and subsequent gallbladder (biliary tract) surgery by 50 per cent.

There was a slight, but statistically non-significant increase in cancer incidence among HRT users. Breast cancer rates were 27 per cent higher in the HRT group and lung cancer incidence was 39 per cent higher. Women who used HRT also tended to have more hip fractures. The researchers conclude that HRT does not reduce cardiovascular events in women with heart disease and increases the risk of blood clots, gallstones, and hip fractures.
A larger trial involving 27,348 healthy women on HRT has just concluded that HRT increases the risk of blood clots, stroke and heart attacks in these women and may increase the risk of breast cancer. NOTE: This study was funded by Wyeth-Ayerst Research, a pharmaceutical company.
Grady, Deborah, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy. Journal of the American Medical Association, Vol. 288, July 3, 2002, pp. 49-57
Hulley, Stephen, et al. Noncardiovascular disease outcomes during 6.8 years of hormone therapy. Journal of the American Medical Association, Vol. 288, July 3, 2002, pp. 58-66 Petitti, Diana B. Hormone replacement therapy for prevention. Journal of the American Medical Association, Vol. 288, July 3, 2002, pp. 99-101
Tanne, Janice Hopkins. Hormone trial for disease prevention stopped early. British Medical Journal, Vol. 325, July 13, 2002, p. 61

Editor's comment: There has been some hope that HRT may help prevent Alzheimer's disease. A recent study, however, demolished this notion. It is now clear that HRT has no health benefits - quite the contrary - and that there is no medical justification for prescribing it.

Sun avoidance increases cancer risk
NEWPORT NEWS, VIRGINIA. There is ample evidence that lack of sun exposure increases the risk of many types of cancer. The mortality rates for breast cancer, prostate cancer, colon cancer, ovarian cancer, and non-Hodgkin lymphoma are twice as high in the northeastern part of the US as in the southwest. Dr. William Grant, PhD, an independent American researcher, now reports additional evidence indicating the eight more cancers are associated with lack of exposure to UV-B radiation (sunshine!). Dr. Grant found a clear inverse correlation between UV-B exposure and mortality from bladder, kidney, lung, pancreatic, stomach, rectal, esophageal cancers and cancer of the corpus uteri. He estimates that over 21,000 white Americans, 1400 African Americans, and 500 people from Asian and other minorities die prematurely every year from cancer because they don't get enough sunshine.
Dr. Grant and most other researchers in the field believe that the lack of sun exposure leads to a vitamin- D deficiency, which is known to be implicated in the progression of many cancers. Vitamin D is formed in the skin when it is exposed to sunlight. Vitamin D formation is totally inhibited by sunscreens and most clothing. Dr. Grant points out that winter time UV-B levels in Boston are insufficient to promote vitamin D synthesis in the skin. He advocates prudent sun exposure when it is available and vitamin D supplementation when it is not. Editor's Note: If lack of sun exposure is a problem in northern USA then it is obviously even more of a problem in Canada. Researchers at the University of Toronto recently concluded that Canadians need to supplement with 4000 IU/day of vitamin D when they are not exposed to sunshine.
Grant, William B. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer, Vol. 94, March 15, 2002, pp. 1867-75

Breast cancer and hormone replacement therapy
SEATTLE, WASHINGTON. Several studies have found an increased risk of breast cancer among postmenopausal women on hormone replacement therapy (HRT). Researchers at the Fred Hutchinson Cancer Research Center now confirm this connection. Their study involved 705 postmenopausal women who had been diagnosed with primary invasive breast cancer and 692 age-matched controls. Recent long-term users of HRT, whether estrogen alone or estrogen plus progestin, were found to have a 60-80 per cent increased risk of breast cancer. The risk increase was particularly high for lobular breast cancer. Women who had been on HRT for 57 months or more had a three-fold increased risk for this type of cancer while women who were currently on combination therapy (estrogen plus progestin) had a four-fold increase in the risk of lobular breast cancer.
The researchers also noted that women who had had two or more screening mammograms were twice as likely to have been diagnosed with breast cancer as were women who had never had a mammogram. Even having just one screening mammogram increased the chance of a diagnosis of breast cancer by almost 60 per cent.
Chen, Chi-Ling, et al. Hormone replacement therapy in relation to breast cancer. Journal of the American Medical Association, Vol. 287, February 13, 2002, pp. 734-41

Breast cancer and electromagnetic radiation
SEATTLE, WASHINGTON. Several studies have found a correlation between low nighttime melatonin levels and the risk of breast cancer. It is believed that low melatonin levels stimulate the pineal gland to call for the production of more estrogen, a significant risk factor for breast cancer.
Researchers at the Fred Hutchinson Cancer Research Institute now report that nighttime exposure to electromagnetic fields commonly found in the home (60 Hz) can suppress melatonin production. The study involved 200 women aged 20 to 74 years with no history of breast cancer. The women participated in two 72-hour trials over a span of 6 to 12 months (to include the variable of seasonal change in the number of hours of darkness). The researchers measured the levels of light and electromagnetic radiation in the women's bedrooms during the night, tested urine samples for the level of 6- sulfatoxymelatonin (the major metabolite of melatonin), and conducted interviews to determine alcohol usage, smoking status and use of medications.
The researchers conclude that exposure to higher magnetic fields during the night is associated with a significant decrease in melatonin production. Melatonin production was also highly dependent on the number of hours of darkness (the more dark hours the more melatonin is produced). Increasing age and alcohol consumption was also associated with reduced melatonin production as was the use of certain classes of medications (beta-blockers, calcium channel blockers and psychotropics). NOTE: This study was partially funded by the Electric Power Research Institute.
Davis, Scott, et al. Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. American Journal of Epidemiology, Vol. 154, October 1, 2001, pp. 591-600

Physical activity and breast cancer risk
CALGARY, CANADA. Canadian researchers have released the results of a major study evaluating the effect of lifetime physical activity on breast cancer risk. The study included 1233 women with breast cancer and 1237 controls and was conducted in Alberta during the period 1995-97. All study participants underwent comprehensive interviews to determine their lifetime physical activity level, diet, smoking status, alcohol consumption, reproductive history, and body measurements. The researchers found no correlation between lifetime physical activity level and breast cancer risk in premenopausal women. Among postmenopausal women, however, they observed a clear risk reduction with increased household and occupational physical activity, but not with increased recreational physical activity. Women who had been most active during their lifetime (household and occupational) had an almost 40 per cent lower risk of breast cancer than did less active women. Active women who did not consume alcohol had a 61 per cent lower risk and active women who had not had any children (nulliparous) had a 78 per cent risk reduction. The researchers conclude that a high level of physical activity over a lifetime reduces the risk of breast cancer in postmenopausal women.
Friedenreich, C.M., et al. Case-control study of lifetime physical activity and breast cancer risk. American Journal of Epidemiology, Vol. 154, August 15, 2001, pp. 336-47

Glucarate and breast cancer prevention
LAWRENCEVILLE, NEW JERSEY. So far the "war on cancer" initiated by President Nixon in 1971 has had a fairly limited success. In 1971 a total of 635,000 new cases of cancer was diagnosed in the USA; by the year 2000 this number had risen to 1,225,000 - an increase of 93 per cent. The number of new cases of breast cancer has increased by about 61 per cent since 1973 and now stands at 184,000 annually. A 1991 report issued by the US Government Accounting Office concluded that there had been no progress in the prevention of breast cancer or in reducing mortality from breast cancer.
Researchers at the Simone Protective Cancer Institute point out that perhaps 90 per cent of all cancers are caused by dietary or nutritional factors. It is also clear that inadequate removal or detoxification of carcinogenic substances in the body plays a significant role in cancer initiation and progression. Evidence is mounting that a simple natural compound, glucarate, found in many vegetables and fruits is very effective in boosting the immune system and detoxifying the body. Calcium glucarate converts to D- glucaric acid in the stomach and is the precursor of the enzyme glucuronyl transferase. This enzyme binds to carcinogens like polycyclic aromatic hydrocarbons, nitrosamines, and steroids and safely excretes them. Animal experiments have found glucarate effective in inhibiting cancers of the colon, skin, lung, and breast and it alone or in combination with vitamin A has been found to inhibit the growth of human breast cancer cells. Glucarate is effective in doses from 1 gram/kg of body weight to 27 grams/kg of body weight.
Simone, Charles B., et al. Cancer, lifestyle modification and glucarate. Journal of Orthomolecular Medicine, Vol. 16, No. 2, 2nd Quarter 2001, pp. 83-90 [86 references]
Webb, T.E., et al. Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate/retinoid combination. Anticancer Research, Vol. 13, No. 6A, November-December 1993, pp. 2095-99

Fats and breast cancer
MILAN, ITALY. The association between the intake of various fats and oils and the risk of breast cancer has been the subject of several studies. There is still no real consensus as to which fats are beneficial and which are not. The evidence for a protective role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main components of fish oils, is probably the strongest.
Researchers at the Italian National Cancer Institute have just completed an investigation aimed at clarifying the association between fat intake and breast cancer risk. A total of 4052 postmenopausal women were followed for an average of 5.5 years. During this time 71 cases of invasive breast cancer were diagnosed. The cancer patients were matched with 141 controls. All study participants had blood samples drawn and red blood cell (erythrocyte) membranes were analyzed for their fatty acid content. The researchers point out that erythrocyte membranes are good biomarkers for not only dietary fat intake, but also for other dietary and hormonal factors.
Women with DHA concentrations in the highest tertile had less than half the risk of breast cancer than did women in the lowest tertile. Polyunsaturated fatty acids overall were also protective with omega-3 acids being somewhat more protective than omega-6 acids. Saturated fatty acid concentrations were not significantly related to breast cancer risk. A higher concentration of monounsaturated fats, especially oleic acid, was associated with a significantly increased risk. The researchers point out that most oleic acid in mammalian tissue is derived from saturated stearic acid through a process involving the enzyme delta 9-desaturase. Saturated fatty acids, cholesterol, carbohydrates, insulin, testosterone, and estrogen all activate this enzyme whereas dietary polyunsaturated fatty acids and fasting deactivate it. The researchers conclude that the delta 9-desaturase enzyme may be an important link between breast cancer risk and dietary fat consumption and urge further research in the field.
Pala, Valeria, et al. Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study. Journal of the National Cancer Institute, Vol. 93, July 18, 2001, pp. 1088-95

Night work increases breast cancer risk
COPENHAGEN, DENMARK. Researchers at the Danish Institute of Cancer Epidemiology report that women who predominantly work at night have a 50 per cent higher risk of developing breast cancer than do women who mainly work during the day. Their study involved 7035 women with breast cancer and 7035 healthy controls. The researchers found that women who had worked predominantly (more than 60 per cent) at night for as little as six months of their working career had a 50 per cent greater incidence of breast cancer. The risk increase was particularly pronounced among flight attendants and catering employees and rose to 70 per cent with long-term (longer than six years) nighttime employment. The increased risk was independent of social status, number of children, and other known breast cancer risk factors. The researchers conclude that exposure to light during the night suppresses the production of melatonin. Melatonin has been found to protect against tumor development, possibly through an enhanced immune response and the scavenging of free radicals. Editor's Note: Even exposure to relatively weak light during the night rapidly decreases melatonin production. It may well be that one of the best protective measures against breast cancer is to sleep in a totally dark room.
Hansen, Johnni. Increased breast cancer risk among women who work predominantly at night. Epidemiology, Vol. 12, January 2001, pp. 74-77

Breast cancer in women under 40 years
MILAN, ITALY. Breast cancer is relatively uncommon in women under 40 years of age (less than 10 per cent of all cases). This explains why most work on defining risk factors has centered on older women. A team of Italian researchers has released the results of a major study aimed at determining the risk factors for younger women. The study involved 579 women aged 22 to 39 years who had been diagnosed with breast cancer and 668 age-matched controls without breast cancer. The women who started menstruating at 15 years of age or older were found to have half the risk of the women who had their first period before the age of 12 years. The women who had their first child when 30 years or older had a five times greater risk of breast cancer than the women who gave birth before the age of 20 years. The women who had never given birth had about half the risk of breast cancer than did the women who had given birth to one or two children. NOTE: This association is contrary to that found for older women.
Use of oral contraceptives and abortions, whether induced or spontaneous, did not have a statistically significant impact on breast cancer risk. A family history of breast cancer, a history of benign breast disease, and higher education levels were associated with an increased risk whereas a high body mass index (overweight) conferred a decreased risk.
Tavani, A, et al. Risk factors for breast cancer in women under 40 years. European Journal of Cancer, Vol. 35, September 1999, pp. 1361-67 [48 references]

More on breast cancer and paroxetine
TORONTO, CANADA. In the August 2000 issue of IHN we reported on the findings of Dr. Michelle Cotterchio and colleagues (New England Journal of Medicine, Vol. 342, June 29, 2000, p. 2003) to the effect that the use of the antidepressant paroxetine (Paxil) may increase the risk of breast cancer by a factor of seven. If confirmed these findings would almost certainly lead to a caution against prescribing paroxetine to women. Not surprisingly, Dr. Cotterchio's report has caused a considerable stir within the medical and pharmaceutical communities. The December issue of the American Journal of Epidemiology contains two letters (one from the manufacturer of paroxetine, SmithKline Beecham Pharmaceuticals) that question the validity of Dr. Cotterchio's conclusions.
The authors of both letters point out that the number of cases of possible paroxetine-related breast cancer was small (9 cases and 1 control) and the SmithKline Beecham letter also makes the observation that most of the patients who had taken paroxetine had previously been exposed to fluoxetine (Prozac). Dr. Cotterchio replies that her report concluded that "the use of paroxetine may be associated with a substantial increase in breast cancer" and that future studies would be required in order to confirm this. She also reiterates that, while she and her team do not suggest that paroxetine is a carcinogen (cancer initiator), they do believe that it could well be a promoter of breast cancer. She points out that animal studies support the hypothesis that antidepressants may be tumor promoters. It would seem that the final conclusion on the possible relationship between paroxetine and breast cancer must await the completion of the larger study.
Antidepressant medication use and breast cancer risk. American Journal of Epidemiology, Vol. 152, December 1, 2000, pp. 1104-05 (letters to the editor)

Antidepressants and breast cancer
TORONTO, CANADA. There is some evidence from animal experiments that antidepressants may promote breast cancer tumors. One case-control study found an association between the use of tricyclic antidepressants and breast cancer risk, but the data concerning SSRIs (selective serotonin reuptake inhibitors) is inconsistent. Researchers at the University of Toronto now confirm that long-term use of tricylic antidepressants is indeed associated with an increased incidence of breast cancer. The study involved 700 women with breast cancer (aged 25 to 74 years) and 700 age-matched controls. A comparison of the use of antidepressants between the cases and the controls found no significant overall differences in breast cancer risks. However, when evaluating the data in detail the researchers discovered that women who had used tricyclic antidepressants for 25 months or more had twice the risk of developing breast cancer as had women who had not used these antidepressants. They also noted that women who had used the SSRI antidepressant paroxetine (Paxil) for more than two weeks had a seven times greater risk of breast cancer even when other possible risk factors were fully accounted for. The researchers caution that the number of women using paroxetine was quite small and recommend larger trials to confirm their initial finding. They do point out though that paroxetine stimulates prolactin secretion and is a potent inhibitor of the cytochrome P450 2D6 enzyme, both factors in an increased breast cancer risk.
Cotterchio, Michelle, et al. Antidepressant medication use and breast cancer risk. American Journal of Epidemiology, Vol. 151, May 15, 2000, pp. 951-57

Antibiotics linked to breast cancer
HELSINKI, FINLAND. Recent research has shown that a low body level of the lignan enterolactone is associated with an increased risk of breast cancer. It is also known that the enterolactone level in body fluids is strongly reduced by common antibiotics. Researchers at the Finnish National Public Health Institute pondered these findings and decided to investigate if there is a connection between the use of antibiotics and the development of breast cancer. They began their study during the period 1973-77 when 9461 cancer- free women between the ages of 19 and 89 years underwent a thorough medical examination (including urine analysis for bacteriuria) as part of the Finnish Mobile Clinic Health Examination Survey. The women were asked about their history of urinary tract infections and the use of antibiotics to treat these infections. At the final follow-up in 1991 157 of the women had developed breast cancer.

The researchers found that women under 50 years of age (at the start of the study) who had used antibiotics to treat urinary tract infections had a 93 per cent excess risk of developing breast cancer when followed-up for more than 10 years. The risk was greatest among younger women and lowest among women aged 60 years or more at entry to the study. It was also clear that urinary tract infections as such were not associated with an excess breast cancer risk; it was only when treated with antibiotics that a strong correlation showed up. The study also confirmed already known risk factors for breast cancer such as age, higher level of education, alcohol consumption, none or only a few childbirths, living in an urban or industrial area, and being lean and tall. The correlation between antibiotics treatment and breast cancer held true even when adjusted for these factors. The researchers conclude that there may be a correlation between breast cancer and the use of antibiotics to treat urinary tract infections at a premenopausal age. They suggest that this conclusion is biologically plausible, but recommend further large-scale studies to confirm it.
Knekt, P., et al. Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer? British Journal of Cancer, Vol. 82, No. 5, March 2000, pp. 1107-10

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Breast cancer risk linked to fatty acid profile
CHAPEL HILL, NORTH CAROLINA. Breast cancer rates differ greatly between countries. They are 5 times higher in the United States than in Japan and twice as high in France as in neighbouring Spain. Differences in overall fat consumption in these countries have been extensively studied, but no link to breast cancer incidence has been detected so far. A large team of researchers from the Netherlands, Ireland, Spain, Finland, Switzerland, Germany and the United States now report that, while overall fat consumption may not be significant, the make-up of the fats could be. As part of the large EURAMIC Study the researchers investigated the link between the content of polyunsaturated fats in adipose (fat) tissue of postmenopausal women and breast cancer incidence. A total of 291 women with breast cancer and 351 controls were included in the study which involved 5 European medical centers. The women all had samples of adipose tissue taken (from the buttocks) and analyzed to determine the concentration of the main polyunsaturated fatty acids: the omega-3 acids - alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the omega-6 acids - linoleic acid (LA) and its metabolite arachidonic acid (AA).

The study found no significant correlation between omega-3 fatty acid levels and breast cancer incidence, but did find a trend to increasing incidence with increasing levels of omega-6 fatty acids in the adipose tissue samples. The researchers also found a significant association between the ratio of EPA and DHA to LA levels and breast cancer incidence in 4 out of 5 of the medical centers involved in the study. Pooling all results showed that women with the highest ratio had a 35% lower breast cancer incidence than women with the lowest ratio. In other words, women with a relatively high adipose tissue level of EPA and DHA (the main components of fish oils) and a relatively low level of LA and its metabolites had a lower breast cancer risk. The researchers note that LA (linoleic acid) is the precursor of certain eicosanoids which may promote tumour growth. EPA and DHA inhibit the production of these harmful compounds and may also, on their own, inhibit tumour growth. The researchers also point out that several epidemiological studies have found an inverse correlation between fish consumption and breast cancer incidence and urge further studies to determine the relationship between the dietary intake of specific fatty acids and breast cancer risk.
Simonsen, Neal, et al. Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC Study. American Journal of Epidemiology, Vol. 147, No. 4, 1998, pp. 342-52

Mammography: A risky procedure?
ABERDEEN, SCOTLAND. Researchers at the University of Aberdeen warn that the compressive force used in order to obtain usable mammograms may be a contributing factor to breast cancer. The British standard for the force used to squeeze the breast as flat as possible corresponds to placing twenty 1 kilogram bags of sugar on each breast. The researchers fear that this force may be excessive and enough to dislocate and spread any existing cancer cells. Animal experiments have shown that the number of cancer sites can increase by as much as 80% when tumors are manipulated mechanically. A recent study in Malmo, Sweden found that the death rate from breast cancer among women under 55 was 29% higher in a group which had been screened with mammography than in the unscreened control group. The screening procedure used "as much compression force as the women could tolerate".
The Lancet, July 11, 1992, p. 122

Estrogen treatment increases risk of breast cancer
UPPSALA, SWEDEN. Swedish and American researchers have confirmed that estrogen replacement therapy for the menopause increases the risk of breast cancer. The study involved over 23,000 women and was begun in 1977. The same researchers have now concluded that periodic administration of progestogen in conjunction with estrogen therapy does not protect against an increased breast cancer risk but may in fact increase the hazard.
The Lancet, October 24, 1992, pp. 1044

Breast cancer rates related to fat intake
LEUVEN, BELGIUM. Researchers at the University of Leuven have completed a study to determine the relationship between fat intake and breast cancer rates in 30 countries. They used nutritional surveys as well as dietary data supplied by the United Nations. They found that breast cancer rates were highly correlated with the intake of animal fats. Intake of fat from fish on the other hand, appeared to have a protective effect. The detrimental effects were greatest in women over 50. The researchers also found a lag time of about 10 years between breast cancer rates and changes in fat intake or compostion.
Sasaki, Satoshi, et al. An ecological study of the relationship between dietary fat intake and breast cancer mortality. Preventive Medicine, March 1993, pp. 187-202

DDT implicated in breast cancer
NEW YORK, NY. Researchers at the New York University Medical Center have recently completed a study to determine the association between breast cancer and exposure to DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls). They studied 14,290 women enrolled in the University's Women's Health Study between 1985 and 1991. After adjusting for other variables known to influence breast cancer rates they found that women with the highest serum concentration of DDT metabolites had a four-fold higher risk of developing breast cancer than did women with the lowest concentration. PCB levels in the blood on the other hand, did not relate signficantly to breast cancer rates. The researchers point out that the incidence of breast cancer in the U.S. increased by 8% in women under 50 but by 32% in women over 50 during the period 1973 to 1980. They speculate that women who had heavy exposure when DDT was widely used (between 1945 and 1972) are now at greater risk than are younger women.
Wolff, Mary S., et al. Blood levels of organochlorine residues and risk of breast cancer. Journal of the National Cancer Institute, Vol. 85, No.8, April 21, 1993, pp. 648-52

Hereditary nature of breast cancer exaggerated
BOSTON, MASSACHUSETTS. Family history appears to account for only a small proportion of breast cancer cases among women up to 70 years of age. This is the conclusion of a team of researchers at the Harvard Medical School. The researchers followed 117,988 female nurses from 1976 to 1988. During this time they identified a total of 2389 cases of invasive breast cancer. Only 2.5% of these cases were attributable to a family history of breast cancer. In other words, other factors are far more important in the development of breast cancer than inherited genes. Nevertheless, women whose mother or sister has been diagnosed with breast cancer are at a higher relative risk. Thus women whose mother had been diagnosed with breast cancer before the age of 40 had twice the risk of developing breast cancer than did women with no maternal history of cancer. The risk decreased as the age of the mother at the time of diagnosis increased. Having a sister with diagnosed breast cancer also approximately doubled the risk and having both a mother and a sister with diagnosed breast cancer carried a relative risk of 2.5. Having a mother and/or sister with breast cancer did not affect a woman's risk of developing cancer at an early age.
Colditz, Graham A., et al. Family history, age, and risk of breast cancer. Journal of the American Medical Association, Vol. 270, No. 3, July 21, 1993, pp. 338-43

Induced abortion may increase breast cancer risk
SEATTLE, WASHINGTON. Researchers at the Fred Hutchinson Cancer Research Center in Seattle have concluded that induced abortion may increase the risk of breast cancer. Their study involved 845 white women born after 1944 who had been diagnosed with breast cancer and 961 randomly chosen controls. The researchers found that women younger than 18 years or older than 30 years who had undergone an induced abortion were twice as likely to develop breast cancer later in life than were women who never had an abortion. Having an abortion between the 9th and 12th week of pregnancy was also associated with a two-fold increase in breast cancer risk. Overall, the risk of developing breast cancer was found to be 50 per cent higher for women who had had an abortion than for women who had never had an abortion. This increased risk did not depend on whether the induced abortion preceded or followed a first birth. The increased risk for breast cancer was similar for women who had one or more than one induced abortion. There was, however, no evidence that having a spontaneous abortion (miscarriage) increased the risk of breast cancer. The researchers caution that their results are at odds with the findings of many other epidemiologic studies and that additional studies are required in order to firmly settle the question of a possible relationship between induced abortion and the later development of breast cancer.
Daling, Janet R., et al. Risk of breast cancer among young women: relationship to induced abortion. Journal of the National Cancer Institute, Vol. 86, No. 21, November 2, 1994, pp. 1584-92

Estrogen therapy may promote metastatic breast cancer
ROCHESTER, MINNESOTA. The administration of estrogen in low doses is believed to stimulate the growth of breast cancer cells. For this reason most doctors do not recommend estrogen replacement therapy for women with a history of breast cancer. Researchers at the Mayo Clinic now report that withdrawal of estrogen replacement therapy in postmenopausal women with metastatic breast cancer can lead to a regression of the cancer. Their study involved four postmenopausal women, three of whom had previously been diagnosed with breast cancer and operated upon. All four women were on estrogen replacement therapy to alleviate menopausal symptoms when they developed cancer in the bones or lungs. The reseachers stopped the estrogen therapy when the metastatic cancers were discovered and the cancers then regressed to the point where they almost disappeared; the improvement lasted for two to three years. The researchers recommend that estrogen withdrawal be the first treatment option for women who develop metastatic breast cancer while on estrogen replacement therapy.
Dhodapkar, Madhav V., et al. Estrogen replacement therapy withdrawal and regression of metastatic breast cancer. Cancer, Vol. 75, No. 1, January 1, 1995, pp. 43-46

Hormone replacement therapy increases risk of breast cancer
BOSTON, MASSACHUSETTS. Estrogen replacement therapy has long been used to alleviate menopausal symptoms. There have also been some indications that long-term use may reduce the risk of ischemic heart disease and osteoporosis. Therapy with estrogen alone is, however, known to increase the risk of endometrial cancer significantly. To avoid this problem the tendency has been to prescribe a combination of estrogen and progestin rather than estrogen alone. Now researchers at the Harvard Medical School have discovered that both estrogen and estrogen/progestin therapy markedly increase the risk of developing invasive breast cancer, especially among older women. Women between the ages of 60 and 64 years were found to have a 71 per cent greater risk of developing breast cancer if they had used hormone replacement therapy for five years or more. Women who had taken hormones for five years or more had a 45 per cent greater risk of dying from breast cancer than women who had never used hormones. Women who stopped their hormone therapy were still at increased risk for two years but then their risk dropped to the level of women who had never used hormones. The researchers recommend that women over 55 years of age carefully consider the risks and benefits of long-term (> five years) hormone replacement therapy. They point out that estrogen by itself, estrogen plus progestin, and progestin alone all increase the risk of breast cancer significantly. They also question the value of hormone therapy for women with few risk factors for heart disease and point out that estrogen therapy for seven years or less is not likely to protect against osteoporotic fractures later in life.
Davidson, Nancy E. Hormone-replacement therapy - Breast versus heart versus bone. The New England Journal of Medicine, Vol. 332, No. 24, June 15, 1995, pp. 1638-39
Colditz, Graham A., et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. The New England Journal of Medicine, Vol. 332, No. 24, June 15, 1995, pp. 1589-93

Smoking increases risk of breast cancer
HJORRING, DENMARK. Some scientists have reported that cigarette smoking may reduce the risk of breast cancer. Now medical doctors at the hospital in Hjorring and researchers at Aarhus University refute this theory. The researchers studied 3,240 women with a median age of 45 years (range 15 to 92 years) who had been referred for mammography; 1,820 of the women were smokers and 1,412 were non-smokers. A total of 230 cases of breast cancer were found among the women. Statistical analysis showed that women who had smoked for 30 years or more had a 60 per cent greater risk of developing breast cancer than did women who had never smoked. Smokers also tended to get breast cancer earlier than did non-smokers. The median age of smokers when breast cancer was detected was 59 years as compared to 67 years for non-smokers.
Bennicke, Kim, et al. Cigarette smoking and breast cancer. British Medical Journal, Vol. 310, June 3, 1995, pp. 1431-33

Insulin-like growth factors linked to cancer
NEWCASTLE, ENGLAND. It has become increasingly apparent over the past five years that insulin-like growth factors (IGFs) play an important role in the proliferation of cancer cells. Now British researchers present evidence that they may be involved in the initial transformation of healthy cells into malignant cells as well. Recent research has also uncovered the fact that women with breast cancer tend to have higher levels of both insulin and IGF-I in their blood. Patients who suffer from acromegaly (abnormal increase in the size of hands, feet, and face) also tend to have increased IGF-I levels and are more prone to the development of colonic polyps (premalignant lesions often leading to colon cancer). Milk is a potent source of IGFs and IGF levels are higher in milk from cows treated with bovine growth hormone (BST). IGFs appear to be destroyed in the human gastrointestinal tract; however, researchers now admit that there is a possibility that IGFs from dairy products could be involved in cancers of the gastrointestinal tract.
Westley, B.R. and May, F.E.B. Insulin-like growth factors: the unrecognised oncogenes. British Journal of Cancer, Vol. 72, No. 5, November 1995, pp. 1065-66

Free radicals implicated in spread of breast cancer
SEATTLE, WASHINGTON. There is substantial evidence that free radical attacks on DNA are a major factor in the initiation of cancer. Now researchers at the Pacific Northwest Research Foundation and the University of Seattle report that free radicals, specifically hydroxyl radicals, are intimately involved in the spread (metastasis) of breast cancer. The researchers studied breast tissues from 12 women with invasive ductal carcinoma but no lymph node involvement, 25 women with metastasized invasive ductal carcinoma, and 21 women with no evidence of breast cancer. Using highly sensitive analysis techniques (FT-IR spectroscopy and GC-MS) the researchers determined that women with metastasized breast cancer exhibit twice as much free-radical damage to the breast tissue DNA than do women with localized cancer. They also found a clear correlation between the growth of metastatic tumours and the extent of radical-induced DNA damage. The researchers conclude that antioxidants, especially vitamin C, may play a crucial role in controlling free radical damage to the DNA in breast tissue and may help prevent metastasis.
Malins, Donald C., et al. Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage. Proceedings of the National Academy of Sciences USA, Vol. 93, No. 6, March 19, 1996, pp. 2557-63

Survival rate better for breast cancer victims if mother had it too
SEATTLE, WASHINGTON. Women whose mother or sister had breast cancer are at greater risk of developing the disease themselves. It is therefore welcome and somewhat surprising news that these women with a first-degree family history of breast cancer have a much better survival rate if they do get breast cancer than do women with no such family history. Researchers at the Fred Hutchinson Cancer Research Center have just released a report which concludes that young breast cancer victims with a mother or sister who had breast cancer have a 50 per cent lower risk of dying from the disease than do women with no family history of breast cancer. Their study involved 733 non- adopted women born after 1944 who had been diagnosed with invasive breast carcinoma between January 1983 and April 1990. By the end of 1994 (average follow-up was 77 months) twice as many women had died in the group with no family history of breast cancer as in the group where a mother or sister had also had breast cancer. This relationship held true even after adjustment for such other factors as age at time of diagnosis, tumor size, bilaterality (cancer in one or both breasts), and whether or not the women had had one or more mammograms prior to diagnosis. The researchers speculate that the better survival rate may be due in part to the less aggressive nature of the type of tumors common in genetically predisposed women.
Malone, Kathleen E., et al. Family history and survival of young women with invasive breast carcinoma. Cancer, Vol. 78, No. 7, October 1, 1996, pp. 1417- 25

Fat intake and risk of breast cancer
STOCKHOLM, SWEDEN. An international team of researchers from the Karolinska Institute, the University of Uppsala and the Harvard Medical School has just released a major research study dealing with the relationship between fat intake and the risk of breast cancer. The study which began in 1987 involved over 61,000 Swedish women born between 1914 and 1948. The women completed a food frequency questionnaire listing 67 commonly eaten foods and also answered more specific questions about their fat consumption. Between March 1987 and March 1993 a total of 674 confirmed cases of invasive breast cancer occurred among the women. Analysis of the collected data showed that a high intake of monounsaturated fats (eg. olive oil) is protective against breast cancer while a high intake of polyunsaturated fats significantly increases the risk of developing breast cancer. A five-gram increment in the daily intake of polyunsaturated fats was found to correspond to a 69 per cent increase in risk. The largest contributor to polyunsaturated fat intake was margarine at 33 per cent followed by bread and cereals at 23 per cent, meat at 17 per cent, and dairy products at 11 per cent. The main polyunsaturated fat in the Swedish diet is linoleic acid. The researchers found no correlation between the intake of saturated fats and breast cancer risk nor between total fat intake (after adjustment for total energy intake) and risk although the already known association between body mass index and breast cancer risk was confirmed by the study. Note: Linoleic acid, an n-6 polyunsaturated fatty acid, should not be confused with linolenic acid, and n-3 polyunsaturated fatty acid. Alpha-linolenic acid (found in flax oil) has actually been found to be beneficial in some cases of breast cancer.
Wolk, Alicja, et al. A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer. Archives of Internal Medicine, Vol. 158, January 12, 1998, pp. 41-45

IGF-1 linked to breast cancer
BOSTON, MASSACHUSETTS. There is considerable evidence that high blood levels of insulin-like growth factor 1 (IGF-1) increases the risk of prostate and colon cancers very significantly. Now researchers at the Harvard Medical School report that high IGF-1 levels are associated with an increased risk of breast cancer in premenopausal women as well. Their study involved 32,826 female nurses aged 43 to 69 years who had blood samples taken in 1989-90. The nurses were free of breast cancer at the time of sampling but by June 1, 1994 397 of them had developed the disease. The researchers compared the plasma levels of IGF-1 and its binding protein (IGFBP-3) in blood from the 397 cancer victims with that of 620 age-matched controls. They found no difference among postmenopausal women; however, among premenopausal women younger than 50 years at the time of blood sampling they found a clear correlation between cancer incidence and IGF-1 levels. Women in the upper third of IGF-1 levels were found to have a more than seven times higher risk of developing breast cancer than women in the lower third of IGF-1 levels. This seven-fold risk increase is greater than that of most other breast cancer risk factors with the exception of a strong family history of the disease. The risk increase among all premenopausal women (irrespective of age) was 2.88 when comparing IGF-1 levels in the top tertile (upper one third) with levels in the bottom tertile. The researchers conclude that measuring IGF-1 levels may be useful in the identification of women with a high breast cancer risk. NOTE: Milk from cows treated with synthetic bovine growth hormone (BST) contains high levels of bovine IGF-1 which is identical to human IGF-1. There is growing concern that consumption of BST-milk may increase IGF-1 levels in humans.
Hankinson, Susan E., et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. The Lancet, Vol. 351, May 9, 1998, pp. 1393-96
Holly, Jeff. Insulin-like growth factor-I and new opportunities for cancer prevention. The Lancet, Vol. 351, May 9, 1998, pp. 1373-75 (commentary)

Hormone replacement therapy linked to breast cancer
BOSTON, MASSACHUSETTS. Estrogen supplementation was originally used for relatively short periods to relieve menopausal symptoms. Now it is widely used on a long-term basis to reduce the risk of coronary heart disease and osteoporosis as well. Evidence is accumulating that long-term hormone replacement therapy increases the risk of breast cancer. Says Dr. Graham Colditz, MD of the Harvard Medical School "It is evident that postmenopausal hormones cause breast cancer". Dr. Colditz bases his conclusion on a thorough review of the English language literature dealing with hormones and breast cancer. Investigators at Oxford University re-analysed the original data from 51 epidemiologic studies involving more than 52,000 women with breast cancer and 100,000 without breast cancer. They found that the risk of breast cancer increased by 2.3 per cent for each year of use of postmenopausal hormones. Most of the studies involved the use of unopposed estrogen, but there is no evidence that the addition of progestins lowers the risk significantly. The Oxford University study also concluded that women who had taken hormones for five years or longer had a 35 per cent greater risk of developing breast cancer than did non-users. The data means that for every woman who starts hormone treatment at the age of 50 years and who continues it for 10 years there are six excess cases of breast cancer and for 15 years of use there would be 12 excess cases. Dr. Colditz points out that there is evidence that hormone replacement therapy reduces the risk of heart disease and osteoporosis. However, among women, deaths from cancer still outnumber deaths from heart disease. It is clear that the choice whether to start hormone replacement therapy or not is a difficult one and should be made on an individual basis rather than as a matter of overall healthcare policy.
Colditz, Graham A. Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer. Journal of the National Cancer Institute, Vol. 90, June 3, 1998, pp. 814-23

Breast cancer and meat consumption
COLUMBIA, SOUTH CAROLINA. A high intake of barbequed and fried meats has been linked to an increased risk of colon cancer. Now researchers at the University of South Carolina report that a preference for well-done meat is associated with an increased risk of breast cancer. Their study involved 273 postmenopausal women who had been diagnosed with breast cancer during the period 1992-1994 and 657 age-matched controls. The women all completed a questionnaire designed to determine their intake of various types of red and white (poultry) meat and fish with particular emphasis on the preparation method (grilling, broiling, frying, roasting, boiling, etc.) and the degree of doneness (from rare to very well-done). The researchers found that women who consistently consume their hamburgers, steaks (beef) and bacon very well-done had an almost five times higher risk of breast cancer than did women who consumed these meats rare or medium-done. The researchers also found an increased risk with a higher intake of red meat in general and confirmed that a family history of breast cancer and the use of hormone replacement therapy are associated with an increased breast cancer risk. The consumption of white meat and fish was not associated with an increased risk. The researchers suggest that extended, high temperature cooking of red meats produces significant amounts of heterocyclic amines which are strong carcinogens. In an accompanying editorial scientists at the Harvard Medical School point out that fish and chicken also contain heterocyclic amine compounds and that chicken meat, if cooked and eaten with the skin, would be expected to be carcinogenic as well. The Harvard scientists also warn that the breast cancer risk associated with eating well-done meat must be balanced against the risk associated with the consumption of under-done meat (Escherichia coli infection).
Zheng, Wei, et al. Well-done meat intake and the risk of breast cancer. Journal of the National Cancer Institute, Vol. 90, November 18, 1998, pp. 1724-29
Egan, Kathleen M. and Giovannucci, Edward. Dietary mutagens and the risk of breast cancer. Journal of the National Cancer Institute, Vol. 90, November 18, 1998, pp. 1687-89 (editoral)

Cigarette smoking and breast cancer
BOSTON, MASSACHUSETTS. The association between cigarette smoking and breast cancer is not clear. Researchers at the Boston University Medical Center now report that cigarette smoking is indeed a risk factor but the magnitude of the risk depends on several factors. From a study of 265 women with breast cancer and 765 controls they conclude that ever-active smokers have twice the risk of developing breast cancer when compared to women who have never smoked or been exposed to passive smoke. The risk from cigarette smoking was found to be particularly high in women who had been exposed to second-hand smoke or who had actually been smokers before the age of 12 years. Women who had smoked before the age of 12 years had a 7.5 times higher risk of developing breast cancer than did never-smokers and even exposure to second- hand smoke at an early age increased the risk by a factor of 4.5. Curiously enough, women who began smoking before their first pregnancy and continued after did not have a significantly elevated risk of breast cancer. The researchers conclude that a first exposure to cigarette smoke prior to the development of breast tissue poses the greatest risk for the development of breast cancer. They also speculate that continued smoking after a first pregnancy may actually help prevent breast cancer due to the antiestrogenic effect of tobacco smoke.
Lash, Timothy L. and Aschengrau, Ann. Active and passive cigarette smoking and the occurrence of breast cancer. American Journal of Epidemiology, Vol. 149, January 1, 1999, pp. 5-12

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Vitamin B12 deficiency and breast cancer
BALTIMORE, MARYLAND. Researchers at the Johns Hopkins University report that women with breast cancer tend to have lower vitamin B12 levels in their blood serum than do women without breast cancer. The researchers determined vitamin B12 concentrations in blood samples obtained in 1974 and in 1989 and compared the levels found in 195 women who later developed breast cancer with the levels found in 195 women free of cancer. They found that postmenopausal women with the lowest serum levels of vitamin B12 had a 2.5-4.0 times greater likelihood of being in the breast cancer group than did women with the highest levels. The researchers found no correlation between breast cancer risk and serum levels of folic acid, vitamin B6, and homocysteine.

In a subsequent review of the findings Dr. Sang-Woon Choi, MD of Tufts University points out that serum levels of folate are a poor indicator of levels in tissues and that it may well be that there is a correlation between folate levels in breast tissue and breast cancer risk. Dr. Choi speculates that a vitamin B12 deficiency may lead to breast cancer because it could result in less folate being available to ensure proper DNA replication and repair.
Wu, K., et al. A prospective study of folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer. Cancer Epidemiol. Biomarkers Prev., Vol. 8, March 1999, pp. 209-17
Choi, Sang-Woon. Vitamin B12 deficiency: a new risk factor for breast cancer? Nutrition Reviews, Vol. 57, August 1999, pp. 250-60

Epstein-Barr virus implicated in breast cancer
PARIS, FRANCE. The Epstein-Barr virus (EBV) is a common human herpes virus involved in the development of infectious mononucleosis. The virus has also been associated with Burkitt's lymphoma, Hodgkin's disease, and stomach cancer.
Researchers at the French Institute for Health and Medical Research now provide convincing evidence that EBV may be involved in the development of breast cancer. Their study involved 98 women (73 per cent postmenopausal) and two men with previously diagnosed breast cancer. The researchers extracted biopsy specimens of the tumours from all participants as well as 30 samples of tissue adjacent to the tumours and five samples of lymph nodes with metastasis.
The DNA of all samples was analyzed using the polymerase chain reaction (PCR), Southern blot analysis, and immunohistochemical staining. The researchers found the Epstein-Barr virus in 51 per cent of the tumour samples, but in only 10 per cent of the samples of adjacent breast tissue. The prevalence of EBV was particularly high in tumours associated with aggressive metastasis (more than three lymph nodes involved); here 72 per cent of all tumours showed the presence of EBV as compared to only 44 per cent of tumours associated with three or less positive nodes. EBV was also detected more frequently in tumours that were negative for steroid hormone receptors; such tumours are associated with more aggressive disease and a poor outcome. The researchers conclude that the Epstein-Barr virus may be implicated in the development of breast cancer particularly the more aggressive forms.
Bonnet, Mathilde, et al. Detection of Epstein-Barr virus in invasive breast cancers. Journal of the National Cancer Institute, Vol. 91, August 18, 1999, pp. 1376-81

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