Obesity and the Risk for Premenopausal and Postmenopausal Breast Cancer

Abstract

Obesity has been consistently associated with an increased risk of postmenopausal breast cancer in population-based studies. Conversely, obesity in such studies has been inversely associated with premenopausal breast cancer risk. In a report of data from two large chemoprevention trials, both of which enrolled women at a high risk of breast cancer, obesity was associated with only a modest, nonsignificantly increased risk of postmenopausal breast cancer and a surprising statistically significant 70% increased risk of premenopausal breast cancer (vs. normal weight). The discrepancies between these results and those from previous observational studies may be due to differences in study design and exposure ascertainment or due to inherent biologic differences whereby the obesity-breast cancer association differs for high-risk women in the clinical setting compared with general population, average-risk women in the observational setting. Cancer Prev Res; 5(4); 515-21. Ó2012 AACR.

Body Mass Index and Prognosis of Metastatic Breast Cancer Patients Receiving First-Line Chemotherapy

“…The relationship between overweight and increased breast cancer risk was consistently observed in postmenopausal women (4,5), whereas the association between body weight and premenopausal breast cancer risk is less clear (6)(7)(8). Several lines of evidence also suggest that increased body weight is associated with a worse prognosis: a shorter survival has been observed in obese women with early breast cancer (9)(10)(11)(12) and in those gaining weight after breast cancer diagnosis (13).…”

Obesity and Cancer: Evidence, Postulated Mechanisms and Prospectives

“…Production of estrogens after menopause, mostly takes place in the peripheral adipose tissues, catalyzed by cytochrome P450 dependent enzyme; aromatase enzyme, that converts androgen precursors into estrogens. CYP19 is the gene encoding aromatase and it is thought to be induced in postmenopausal women and not in premenopausal females [16,131]. Therefore, the greater risk of hormone receptor positive breast cancer in a post menopause period of overweight/obese women has been referred, in particular, to elevated estrogen production in adipose tissue by aromatase enzyme as a consequence of hyper adiposity [132].…”

“…It has been demonstrated that elevated circulating levels of free estrogen, as well as estrone and androgens, are associated with breast cancer [31]. Therefore, Increased BMI has been associated with increased the risk of postmenopausal breast cancer not premenopausal breast cancer [16,34,131].…”

“…Even more, obesity has been linked to increase the risk of recurrence, and deaths among cancer patients, thereby, better exploration and comprehensive understanding of the linking mechanisms between obesity and occurrence or aggressiveness of certain cancers, will allow the development of recent strategies against cancer [12][13][14]. While obesity is associated with an increased risk of several malignancies, other types of cancer as squamous cell carcinoma of esophagus, lung and premenopausal breast cancer may exhibit inverse association with obesity [15][16][17]. The concept of association of metabolic dysregulation encountered in obesity and carcinogenesis was firstly enunciated by Otto Warburg [18].…”

Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells

“…Moreover, breast tissues of obese women (Morris et al 2011) as well as mammary glands of genetically modified and dietinduced obese mice (Subbaramaiah et al 2011) were shown to display subclinical inflammation characterized by increased P450 aromatase activity and enhanced NF-kB activity. As inflammation is a hallmark of cancer, the correlation of obesity with 'local' mammary adipocyte dysfunction may provide a rational basis for the increased risk and poor prognosis of breast cancer associated with obesity (Anderson & Neuhouser 2012).…”