LAUSR

Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer (TNBC). Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined associations between genetic ancestry and TDLU involution in normal breast tissue donated by 2,014 healthy women in the US. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR]trend=1.36; 95% CI = 1.07-1.74), acini counts/TDLU (OR = 1.47; 95% CI = 1.06-2.03), and median TDLU span (ORtrend=1.44; 95% CI = 1.08-1.91), indicating lower involution; whereas East Asian descendants were associated with decreased TDLU counts (ORtrend=0.52; 95% CI = 0.35-0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of TNBC in the US and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk.