Obesity rates started rising notably in the United States in the 1980s, and the Black community and especially African American women were disproportionately affected. At the same time, rates of breast cancer increased rapidly, especially for hormone receptor–positive (HR+) disease. A high body mass index (BMI) is a known risk factor for HR+ breast cancer in postmenopausal women and thereby contributes to rising breast cancer incidence trends along with lower parity and increased detection through mammography screening. Notably, rates of HR+ breast cancer increased more rapidly in African American women than White women.
In a sample of 548 patients, 26% were Black, and 74% were White. Sixty-two percent of Black patients and 32% of White patients were obese (BMI ≥ 30 kg/m2; P < .0001). Seventy-five percent of Black patients and 87% of White patients had HR+ tumors (P = .001).
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33288
Obesity has been associated with abnormally high expression of the enzyme aromatase in the breast, increased local estrogen production, and predisposition to breast hyperplasia and cancer. Increased adiposity in postmenopausal women may trigger signaling pathways that induce aromatase expression. In breast adipose fibroblasts, increased TNF production may induce the distal aromatase promoter, whereas increased local PGE2 production may induce the proximal promoter region.
Choice of therapy for hormone dependent breast cancer can also be affected by genetics. Endoxifen (EDX) is a key active metabolite of tamoxifen (TAM) with higher affinity and specificity to estrogen receptors that also inhibits aromatase activity. Tamoxifen is a largely inactive pro-drug, requiring metabolism into its most important metabolite endoxifen. Since the cytochrome P450 (CYP) 2D6 enzyme is primarily involved in this metabolism, genetic polymorphisms of this enzyme, can result in considerably reduced endoxifen formation and as a consequence may affect the efficacy of tamoxifen treatment.
Polymorphisms are phenol