Overweight young women have reduced risk of developing breast cancer before menopause

November 27, 2006

A higher body mass index (BMI), especially in early adulthood, may be associated with a reduced risk of breast cancer before menopause, according to an article in the November 27 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. This association does not appear to be related to ovulation problems that overweight women may develop.

Previous studies have observed an association between higher body mass index and a lower risk of breast cancer, according to background information in the article. High BMI can be associated with irregular or long menstrual cycles and the development of polycystic ovary syndrome, a condition that occurs when the ovaries malfunction, decreasing fertility and contributing to other illnesses. All of these are related to disruptions in ovulation, which decrease levels of the hormones estradiol and progesterone; the long-held belief was that these lower levels, in turn, might explain the decrease in breast cancer risk. "However, few studies have explored whether these or other factors provide mechanistic insights into the unexpected protection that a high body mass confers on the premenopausal breast," the authors write.

Karin B. Michels, Sc.D., Ph.D., Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues studied 113,130 premenopausal women who were part of the Nurses' Health Study II, a large group of female registered nurses who have been followed since 1989. At the beginning of the study, the women provided information about their adult height and their weight at age 18, as well as their current weight, any fertility problems, their family history of breast cancer and the characteristics of their menstrual cycle. Follow-up questionnaires that included questions about breast cancer and benign breast disease, childbirth, alcohol consumption, oral contraceptive use and physical activity were filled out every two years. The women were followed until 2003 or until they developed breast or any other cancer, died or reached menopause, whichever happened first.

Between 1989 and 2003, 1,398 cases of invasive breast cancer occurred among the women. Those with a current BMI of 30 or higher had a 19 percent lower risk of breast cancer compared with those who had a BMI between 20 and 22.4, after adjusting for family history, personal characteristics, lifestyle habits and menstrual variables. Women whose BMI was 27.5 or higher at age 18 had a 43 percent lower risk of developing breast cancer than those whose 18-year-old BMI was between 20 and 22.4. This association did not change when the researchers considered current BMI.

"A high BMI during adulthood is highly correlated with a high body mass during adolescence, which may be more important for the development of breast cancer before menopause," the authors write. "Although a high birth weight has been fairly consistently linked to an increase in the risk of premenopausal breast cancer, the BMI-breast cancer association seems to reverse at some point during the first years of life, only to revert back after menopause," when breast cancer is most often diagnosed.

Because the failure to ovulate (anovulation) cannot be measured directly, these findings do not rule out the hypothesis that factors related to ovulation contribute to the protective effect of a high BMI. "However, because adjustment for menstrual cycle patterns, infertility due to ovulatory disorder, probable polycystic ovary syndrome and use of oral contraceptives did not even slightly attenuate the association with BMI, anovulation does not seem to be a primary explanation for the reduced risk in heavier women," the authors conclude. "Among women with no history of infertility due to an ovulatory disorder, the inverse association between BMI and premenopausal breast cancer incidence persisted, lending further support to the role of mechanisms other than anovulation." The link may be hormonal, or due to the fact that obese women are less likely to be screened for breast cancer.
(Arch Intern Med. 2006;166:2395-2402. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This project was supported by a grant from the Massachusetts Breast Cancer Research Grants Program of the Massachusetts Department of Public Health. The Nurses' Health Study II is supported by a Public Health Service grant from the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org.

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