Association of cumulative lifetime estrogen exposure and reproductive factors with breast cancer molecular subtype among Nigerian women in the MEND study.

PURPOSE: Cumulative lifetime endogenous estrogen exposure (CLEEE) is an established breast cancer (BC) risk factor, yet Nigeria faces increasing BC incidence and mortality despite reproductive patterns typically associated with lower estrogen exposure. We evaluated the association of endogenous estrogen exposure and BC risk in this population.

METHODS

We analyzed 609 Nigerian BC cases and 609 controls from the MEND case-control study to examine associations between CLEEE and BC risk by molecular subtype. CLEEE was defined as time from menarche to menopause (or enrollment), minus pregnancy duration; a breastfeeding-adjusted measure (CLEEE-b) subtracted breastfeeding duration.

RESULTS

Most cases were grade 2 (67.2%) or grade 3 (27.9%), with 42.8% triple-negative breast cancer (TNBC), 33.7% luminal A, 12.6% HER2-enriched, and 10.9% luminal B. Compared with controls (medians), cases had lower BMI (25.4 vs. 26.7, p < 0.001), earlier menarche (mean: 14.9 vs. 15.2 years, p < 0.001), and higher CLEEE (330 vs. 321 months, p < 0.018) and CLEEE-b (273 vs. 264 months, p = 0.043). In multivariable models adjusting for BMI and menopausal status, each standard deviation increase in CLEEE was associated with 33% higher BC odds (aOR 1.33, 95% CI 1.13-1.57), with stronger association for postmenopausal women (aOR: 1.62, 95% CI: 1.22-2.19), women with BMI ≥ 3025 (aOR: 1.52, 95% CI: 1.07-2.20), and for TNBC (highest vs. low CLEEE tertile: aOR 1.90, 95% CI 1.12-3.26). Associations for CLEEE-b remained significant but modestly attenuated.

CONCLUSION

Higher CLEEE was associated with increased BC odds, particularly for TNBC. Larger studies among African women are needed to confirm these associations to inform prevention strategies.