Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations.
Neil M IyengarXi Kathy ZhouHillary MendietaOmar El-HelyDilip D GiriLisle WinstonDomenick J FalconeHanhan WangLingsong MengTaehoon HaMichael PollakMonica MorrowAndrew J DannenbergPublished in: NPJ breast cancer (2021)
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.
Keyphrases
- breast cancer risk
- early onset
- metabolic syndrome
- weight loss
- insulin resistance
- adipose tissue
- type diabetes
- polycystic ovary syndrome
- oxidative stress
- late onset
- bariatric surgery
- high fat diet induced
- high fat diet
- poor prognosis
- pregnant women
- obese patients
- bone mineral density
- skeletal muscle
- dna binding
- transcription factor
- young adults
- childhood cancer