Sex, fat and breast cancer

The worldwide incidence of obesity is now recognized to be of pandemic proportions. Obesity is associated with a number of clinical conditions including type 2 diabetes, cardiovascular problems and cancer. There is now good epidemiological evidence to indicate that obese women are at increased risk of breast cancer. The greater the extent of obesity, the greater the risk; thus we are faced with the daunting prospect that tens of millions more women worldwide may be at risk of breast cancer in their senior years than was previously thought. This potentially poses a major public health problem, yet the underlying cellular and molecular mechanisms linking obesity with breast cancer are not understood. Breast cancer risk also increases with aging and, once again, the underlying mechanisms are not understood. We have addressed these issues, and believe we have now elucidated the mechanisms whereby obesity and aging are related to increased risk of breast cancer. The mechanism involves circulating factors called adipokines as well as sex hormones. We have shown that these factors control a cell signaling pathway believed to be a master regulator of metabolic processes. This pathway in turn we have shown regulates the formation of estrogens in the breast, such that estrogen formation in the breast increases with both obesity and with aging. Since formation in the breast is the major source of estrogen driving breast cancer development in postmenopausal women, this mechanism then provides a link between obesity, aging and breast cancer. Obese individuals frequently find it very difficult to lose and maintain loss of weight by diet and exercise; therefore therapeutic intervention will be necessary to prevent this anticipated new epidemic of breast cancer. The mechanism which we have uncovered will hopefully lead to new therapeutic modalities of intervention in order to break the link between obesity on the one hand and aging on the other, with increased breast cancer risk.