Excess body weight and postmenopausal breast cancer: Emerging molecular mechanisms and perspectives

Abstract

Postmenopausal, obese women have a significantly higher risk of developing estrogen receptor-positive (ER+) breast tumors, that are resistant to therapies and are associated with higher recurrence and death rates. The global prevalence of overweight/obese women has reached alarming proportions and with postmenopausal ER+ breast carcinoma (BC) having the highest incidence among the three obesity-related cancers in females (i.e., breast, endometrial and ovarian), this is of significant concern. Elucidation of the precise molecular mechanisms underlying the pro-cancerous action of obesity in ER+BC is therefore critical for disease prevention and novel treatment initiatives. Interestingly, accumulating data has shown opposing relationships between obesity and cancer in either pre- or post-menopausal women. Excess body weight is associated with an increased risk of breast cancer in postmenopausal women and a decreased risk in pre-menopausal women. Moreover, excess adiposity during early life appears to be protective against postmenopausal breast cancer, including both ER+ and ER negative BC subtypes. Overall, estrogen-dependent mechanisms have been implicated as the main driving force in obesity-related breast tumorigenesis. In the present review we discuss the epidemiologic and mechanistic aspects of association between obesity and breast tumors after menopause, mainly in the context of hormone dependency. Molecular and cellular events underlying this association present as potential avenues for both therapeutic intervention as well as the prevention of BC-promoting processes linked to excess adiposity, which is proving to be vital in an increasingly obese global population.