Weight Loss Cuts Cancer Risk in Women with BRCA Gene



By Neil Osterweil , MedPage Today Staff Writer. Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine. Source News Article: Forbes, MSN



Review: TORONTO, Aug. 19-Women at a high risk for early-onset breast cancer because of mutations in the BRCA1-gene may be able to cut that risk by two-thirds if they lose weight early in adult life.

That's the conclusion of an international team of researchers, who also found that women with harmful BRCA1 mutations who opt to have two or more pregnancies and who gain 10 or more pounds between the ages of 18 and 30 increase their risk of early-onset breast cancer by about 44%.

In contrast, weight losses or gains when women are in their 30s do not seem to influence breast cancer risk either before or after menopause, and weight changes don't appear to affect the cancer risk profiles of women with mutations in BRCA2, a different gene also notorious for its association with early-onset cancer.

The findings by Steven A. Narod, M.D., of the Center for Research in Women's Health at the University of Toronto and colleagues at other centers in Canada, the U.S. and Poland are published in the current issue of the open-access journal Breast Cancer Research.

"Our findings suggest that weight loss in early adult life (and not weight per se) decreases the risk of BRCA-associated breast cancer diagnosed at an early age," Dr. Narod and colleagues wrote. "More specifically, the period between age 18 and 30 years appears to be a critical one when weight gain should be avoided in mutation carriers."

The relationship between a woman's change in weight and her risk for breast cancer appear to be related to menopausal status at the time of diagnosis, the authors noted.

To see whether there could be an association between body weight changes and the risk of breast cancer in women with BRCA1 and BRCA2 mutations, the investigators conducted a matched case-control study pairing 797 women with a deleterious BRCA1 mutation and 276 with a harmful BRCA2 mutation with women matched by age, mutation, country of residence and history of ovarian cancer.

Information about weight was taken from a standard questionnaire given to women with the mutations.

They found that among all women in the study, those who lost at least 10 pounds during the late teens and 20s (ages 18 to 30 years) had a decreased risk of breast cancer from ages 30 to 49 (odds ratio = 0.47; 95% confidence interval (CI) 0.28-0.79). In contrast, women who gained weight during the same interval did not appear to have any change in overall risk.

When the data were broken down according to age of breast cancer diagnosis, however, they found that the protective effect of early weight loss held up only for those whose tumors were diagnosed between the ages of 30 and 40, but not after age 40.

"Although weight loss reduced the risk of breast cancer among carriers of either mutation, this association remained significant only for women with a BRCA1 mutation (OR = 0.35)," Dr. Narod and colleagues wrote.

Among a subgroup of BRCA1 mutation carriers who had at least two children, weight gain of more than 10 pounds between ages 18 and 30 was associated with an increased risk of breast cancer diagnosed between age 30 and 40 (OR = 1.44, 95% CI 1.01-2.04).

Changes in body weight later in life (at age 30 to 40) did not influence the risk of either premenopausal or postmenopausal breast cancer, however.

The authors noted that a large proportion of the women who lost weight started out with a BMI over 25, indicating that they were overweight to begin with and suggesting that genetically at-risk women who are overweight at age 18 might especially benefit from weight loss in early adulthood.

They suggested that the relationship between weight changes and breast cancer risk could be due to metabolic factors such as central adiposity, altered ovarian hormone and glucose metabolism, insulin resistance, hyperinsulinemia, and serum concentrations of insulin-like growth factor 1.

Primary source: Breast Cancer Research. Source reference: Breast Cancer Research 2005, 7:R833-R843 (DOI 10.1186/bcr1293)

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