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

Neil M. Iyengar, Xi Kathy Zhou, Hillary Mendieta, Omar El-Hely, Dilip D. Giri, Lisle Winston, Domenick J. Falcone, Hanhan Wang, Lingsong Meng, Taehoon Ha, Michael Pollak, Monica Morrow, Andrew J. Dannenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number18
Journalnpj Breast Cancer
Volume7
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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