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

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.

Automated summary

Obesity is associated with increased levels of aromatase and inflammation in the breasts of pre-menopausal BRCA1/2 mutation carriers, potentially contributing to the higher risk of early-onset breast cancer in this population. This highlights the importance of understanding the molecular mechanisms underlying the relationship between obesity and breast cancer risk in BRCA1/2 mutation carriers.