TY - JOUR
T1 - Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations
AU - Iyengar, Neil M.
AU - Zhou, Xi Kathy
AU - Mendieta, Hillary
AU - El-Hely, Omar
AU - Giri, Dilip D.
AU - Winston, Lisle
AU - Falcone, Domenick J.
AU - Wang, Hanhan
AU - Meng, Lingsong
AU - Ha, Taehoon
AU - Pollak, Michael
AU - Morrow, Monica
AU - Dannenberg, Andrew J.
N1 - Funding Information:
This work was supported by grants NIH/NCI 1R01CA215797-01 (to A.J. Dannenberg), NIH/NCI U54 CA210184-01 (to A.J. Dannenberg), Conquer Cancer Foundation of the American Society of Clinical Oncology (to N.M. Iyengar), the Breast Cancer Research Foundation (to N.M Iyengar and A.J. Dannenberg), the Botwinick-Wolfensohn Foundation (in memory of Mr. and Mrs. Benjamin Botwinick; to A.J. Dannenberg), Myrna and Bernard Posner (to N.M. Iyengar), and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). We thank all the patients that donated biospecimens to this study and Dr. Clifford A. Hudis for the critical review of the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41523-021-00226-8
DO - 10.1038/s41523-021-00226-8
M3 - Article
AN - SCOPUS:85101816245
VL - 7
JO - npj Breast Cancer
JF - npj Breast Cancer
SN - 2374-4677
IS - 1
M1 - 18
ER -