Title | Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Iyengar 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 |
Journal | NPJ Breast Cancer |
Volume | 7 |
Issue | 1 |
Pagination | 18 |
Date Published | 2021 Mar 01 |
ISSN | 2374-4677 |
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. |
DOI | 10.1038/s41523-021-00226-8 |
Alternate Journal | NPJ Breast Cancer |
PubMed ID | 33649363 |
PubMed Central ID | PMC7921427 |
Grant List | 1R01CA215797-01 / / 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.