Science Spotlight

Complex patterns link obesity and breast cancer

Example of HER2 staining used to classify breast cancers.
Image modified from the web.

Breast cancer is the second most common cancer in women worldwide, representing 16% of all cancers in women. Although early diagnosis and available treatments have improved survival rates, new prevention strategies are sought to reduce the incidence of this disease. Although etiology and risk factors for breast cancer are not yet fully known, a high body mass index might influence breast cancer incidence, since body fats can affect hormonal levels, in particular those of estrogens, which might control the neoplastic transformation.

Even though several studies previously examined this issue, their results were limited by small sample sizes. Collaboration between University of Washington, Fred Hutch and University of New Mexico allowed for a larger study aimed at clarifying the relationship between body mass index and breast cancer. Data from women in Seattle and Albuquerque were obtained from hospitals, oncology and primary care practices, and included clinical information, height and weight at the time of diagnosis, as well as exposure to risk factors such as use of oral contraceptives and menopausal hormone therapy. The association between body mass index, categorized based on WHO criteria in normal, overweight and obese, and breast cancer was calculated using a polytomous logistic regression. The results of the study were published in Breast Cancer Research and Treatment.

Breast cancers were divided based on receptor expression pattern in 1) triple negative (TN), which do not express estrogen receptor (ER), progesterone receptor (PR) or the human epidermal growth factor receptor 2 (HER2), 2) HER2-overexpressing tumors (H2E) and 3) luminal (ER+). TN and HER2 are two particularly aggressive subtypes of breast cancer, characterized by a poorer 5 year-survival rate as compared to luminal cancers. Compared to luminal tumors, no differences in risk were observed with respect to body mass index, height or weight. However, when stratified for menopausal status, weight and body mass index were positively associated with risk for TN as compared to ER+ luminal breast cancer in premenopausal women and negatively associated with TN cancers in postmenopausal women. In postmenopausal women, the conversion of androgen to estrogen in adipose tissue is the primary source of estrogens, and obesity has been shown to cause higher blood levels of circulating estrogens in older women. The observation that obesity may primarily affect ER+ breast cancers is consistent with this mechanism. On the other end, ovaries are the primary source of estrogen in premenopausal women. Obesity can result in reduced menstrual cycles and reduction in estrogen production, which might contribute to the reduced risk of ER+ cancers in obese premenopausal women. Instead, high body mass index was associated with higher risk of TN breast cancer in premenopausal women. The mechanism underlying this finding has not been discovered, but it might be due to non-hormonal changes associated with obesity, such as inflammation or increased levels of insulin or insulin-like growth factors.
A complex scenario emerges from this study, highlighting the need to better understand how body mass index can influence the risk of some breast cancers, but also the need to find other risk factors that can be modified in order to reduce breast cancer incidence.

 The study was supported by the National Cancer Institute.

Chen L,Cook LS,Tang MC,Porter PL,Hill DA,Wiggins CL,Li CI. 2016. Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer. Breast Cancer Res Treat. 157(3): 545-554.


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