Obese adipose tissue in the mammary gland (by Arendt et al. via Cancer Research

Bhardwaj et al. investigated whether high body mass index (BMI) increases breast cancer risks for women carrying BRCA 1 or BRCA2 mutations. They examined noncancerous breast tissue from 69 such women and found that BMI and biomarkers of metabolic dysfunction were positively correlated with DNA damage in epithelia. RNA sequencing data revealed that obesity altered breast adipose microenvironment and activated estrogen biosynthesis. Blocking signaling pathways mediated by either estrogen or obesity-associated factors leptin or insulin, reduced DNA damage. Additionally, a high-fat diet increased DNA damage and mammary tumors in Brca1+/−mice. These results provide mechanistic insight linking obesity and breast cancer in BRCA mutation carriers, and suggest that reducing risk may involve maintaining a lower body weight, addressing metabolic problems and targeting estrogen.

Bhardwaj P, … Brown KA. Sci Transl Med. 2023 Feb 22;15(684):eade1857...

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