Obesity and breast cancer in premenopausal women: Current evidence and future perspectives

There is raising evidence reporting an increased incidence of breast cancer over the past decades. Every year approximately 1.4 million new cases of breast cancer are diagnosed worldwide, with a mortality rate of approximately 450,000/year. Out of these cases, 6.6% are diagnosed in premenopausal women with a median age at diagnosis of 40 years: in premenopausal women breast cancer seems to be more aggressive than in post-menopausal women. Obesity has been reported to increase the risk of developing breast cancer and to worsen the prognosis. This seems to be due to several obesity-related mechanisms. Insulin resistance that often occurs with obesity may results in compensatory hyperinsulinemia. Insulin cross-binds insulin-like growth factor-I receptors expressed on breast cells, resulting in proliferative stimuli on breast cancer cells. Besides, hyperinsulinemia up-regulates the growth hormone receptor (GHR) thus increasing GHR stimulation and resulting in an increased hepatic IGF-I synthesis. Moreover, insulin decreases the hepatic expression of binding proteins of IGF-I, such as insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-2, thus leading to high circulating and bioavailable free IGF-I. Additionally, obesity is associated to chronic low-grade inflammation that has been reported to be an additional stimulus for tumor growth. This review shows the current evidence regarding to the association of obesity and breast cancer in premenopausal state focusing on both human and basic studies; showing that the obesity is a risk factor for breast cancer also among premenopausal women, especially for the molecular subtype Triple Negative Breast Cancer.