Mismatch Repair Protein Loss as a Prognostic and Predictive Biomarker in Breast Cancers Regardless of Microsatellite Instability.

ABSTRACT: Background:Breast cancers that harbor mismatch-repair (MMR) deficiency and/or microsatellite instability (MSI) might be sensitive to immune checkpoint blockade, but there are currently no specific guidelines for assessing MMR status in breast cancer. Here, we sought to define the clinical value of MMR immunohistochemistry (IHC) and MSI analysis in breast cancers. Methods:We subjected 444 breast cancers to MMR IHC and MSI analysis. Cases were classified as MMR-proficient (pMMR), MMR-deficient (dMMR), and MMR-heterogeneous (hMMR) based on the loss of immunoreactivity; MSI was defined by instability in the five indicators recommended by the National Cancer Institute for endometrial and colorectal cancers. Correlation of MMR status with patients' survival was assessed using the Kaplan-Meier estimator. Statistical tests were two-sided. Results:Loss of MMR proteins was homogeneous (dMMR) in 75 patients (17%) and heterogeneous (hMMR) in 55 (12%). Among luminal breast cancers, there were similar frequencies of dMMR and hMMR tumors. Overall, the rate of discrepancy between IHC and MSI analysis was high (91%). Women with Luminal B-like dMMR carcinomas (n?=?44) showed shorter overall survival (median?=?77?months, range?=?0-115?months) than those with pMMR (n?=?205) or hMMR (n?=?35) tumors (median?=?84?months, range?=?0-127?months) (P?=?.008). On the contrary, patients with estrogen receptor-negative breast cancers treated with chemotherapy lived longer in cases of dMMR (n?=?9) than pMMR (n?=?33) or hMMR (n?=?7) tumors, with 87?months of median survival (range?=?73-123?months) for the former compared with 79?months (range?=?8-113?months) for the latter two categories (P?

SUBMITTER: Fusco N 

PROVIDER: S-EPMC6649738 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature