Abstract
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 < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 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.
Highlights
Genomic testing has revolutionized the care of breast cancer patients by identifying individuals with molecularly low-risk tumors who can safely avoid chemotherapy, thereby personalizing breast cancer treatment[1,2,3]
Study cohort Overall, there were 738,762 hormone receptor (HR)-positive, human epidermal growth factor-2 receptor (HER2)-negative patients included in the National Cancer Database (NCDB), of whom 9848 received 70-gene signature (MammaPrint) testing
There were no significant differences in the rate of 70-gene signature testing between patients with invasive lobular carcinoma (ILC) compared to invasive ductal carcinoma (IDC)
Summary
Genomic testing has revolutionized the care of breast cancer patients by identifying individuals with molecularly low-risk tumors who can safely avoid chemotherapy, thereby personalizing breast cancer treatment[1,2,3]. For patients with more advanced clinical factors such as larger tumors, involved lymph nodes, younger age, and higher tumor grade, “clinical risk” can conflict with “genomic risk.” In such discordant situations, the optimal management strategy is unknown. The MINDACT trial sought to address this question by studying the effect of chemotherapy on patients with early-stage breast cancer and discordant risk[4] In this trial, patients with clinical high risk but genomic low-risk tumors were randomized to receive chemotherapy or not based on either clinical or genomic risk status. Studies of genomic assays like the 70-gene signature (MammaPrint) and the 21-gene recurrence score (Oncotype Dx) show that a higher proportion of ILC patients have tumors characterized as low or intermediate risk compared to invasive ductal carcinoma (IDC)[18,19]. (3) to evaluate potential differences in overall survival (OS) by histology and treatment type in those with discordant risk
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