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

TitleEffects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations.
Publication TypeJournal Article
Year of Publication2021
AuthorsIyengar NM, Zhou XKathy, Mendieta H, El-Hely O, Giri DD, Winston L, Falcone DJ, Wang H, Meng L, Ha T, Pollak M, Morrow M, Dannenberg AJ
JournalNPJ Breast Cancer
Volume7
Issue1
Pagination18
Date Published2021 Mar 01
ISSN2374-4677
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.

DOI10.1038/s41523-021-00226-8
Alternate JournalNPJ Breast Cancer
PubMed ID33649363
PubMed Central IDPMC7921427
Grant List1R01CA215797-01 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
U54 CA210184 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U54 CA210184-01 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
R01 CA215797 / CA / NCI NIH HHS / United States
Related Faculty: 
Domenick J. Falcone, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700