Interaction between menopausal status and obesity in affecting breast cancer risk

Abstract

Obesity has a complex relationship to breast cancer risk that differs in premenopausal and postmenopausal women. Before the menopause, the level of adiposity is inversely related to risk, indicative of a protective effect, whereas in postmenopausal women, particularly the elderly, the association is a positive one, consistent with obesity being a risk factor. The importance of high estrogen production in adipose tissue, with consequent elevation of circulating biologically available estradiol, in the promotional effect of obesity on postmenopausal breast carcinogenesis is well established; the resulting tumors express both estrogen and progesterone receptors. The mechanism(s) for the protective effect in premenopausal women is less well understood, but the breast cancers that do develop in the presence of obesity are most often estrogen and progesterone receptor negative, consistent with the selection of non-estrogen-dependent tumor cells which are dependent on growth factors such as insulin, insulin-like growth factor-I and some adipokines. The influence of menopausal status on the relationships between adiposity and breast cancer appears to be modified within each category by age; the protective effect before the menopause may be limited to younger women (<35 years), and the adverse effect was found to apply specifically to older postmenopausal women. Although randomized trials of weight reduction for postmenopausal breast cancer prevention have not been performed, observational studies suggested that risk reduction does occur; in addition, other health benefits of weight control need to be considered regardless of menopausal status.