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When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010–2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%,  p  &lt; 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%,  p  &lt; 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma ( p  = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection.

npj breast cancer

The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study