|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|
|Date Published||2021 Mar 01|
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.
|Alternate Journal||NPJ Breast Cancer|
|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
Domenick J. Falcone, Ph.D.