Feasibility of risk assessment for breast cancer molecular subtypes.

Purpose: Few breast cancer risk assessment models account for the risk profiles of different tumor subtypes. This study evaluated whether a subtype-specific approach improves discrimination.

Methods: Among 3389 women who had a screening mammogram and were later diagnosed with invasive breast cancer we performed multinomial logistic regression with tumor subtype as the outcome and known breast cancer risk factors as predictors. Tumor subtypes were defined by expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) based on immunohistochemistry. Discrimination was assessed with the area under the receiver operating curve (AUC). Absolute risk of each subtype was estimated by proportioning Gail absolute risk estimates by the predicted probabilities for each subtype. We then compared risk factor distributions for women in the highest deciles of risk for each subtype.

Results: There were 3,073 ER/PR+ HER2 - , 340 ER/PR +HER2 + , 126 ER/PR-ER2+, and 300 triple-negative breast cancers (TNBC). Discrimination differed by subtype; ER/PR-HER2+ (AUC: 0.64, 95% CI 0.59, 0.69) and TNBC (AUC: 0.64, 95% CI 0.61, 0.68) had better discrimination than ER/PR+HER2+ (AUC: 0.61, 95% CI 0.58, 0.64). Compared to other subtypes, patients at high absolute risk of TNBC were younger, mostly Black, had no family history of breast cancer, and higher BMI. Those at high absolute risk of HER2+ cancers were younger and had lower BMI.

Conclusion: Our study provides proof of concept that stratifying risk prediction for breast cancer subtypes may enable identification of patients with unique profiles conferring increased risk for tumor subtypes.