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Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in  BRCA1/2  mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal  BRCA1/2  mutation carriers have increased levels of aromatase and inflammation in the breast, as occurs in post-menopausal women. In a prospective cohort study of 141 women with germline  BRCA1  ( n  = 74) or  BRCA2  ( n  = 67) mutations, leptin, and aromatase expression were higher in the breast tissue of obese versus lean individuals ( P  < 0.05). Obesity was associated with breast white adipose tissue inflammation, which correlated with breast aromatase levels ( P  < 0.01). Circulating C-reactive protein, interleukin-6, and leptin positively correlated with body mass index and breast aromatase levels, whereas negative correlations were observed for adiponectin and sex hormone-binding globulin ( P  < 0.05). These findings could help explain the increased risk of early-onset breast cancer in obese  BRCA1/2  mutation carriers.

Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations