Abstract
Background
Very few studies have investigated mismatch repair (MMR) deficiency in breast carcinoma
(BC) in clinical setting. Given the recent approval of Pembrolizumab for solid tumors
with MMR deficiency, we screened clinically advanced breast carcinoma patients for
immunotherapy by examining their MMR status.
Patients and methods
The cohort consisted of 163 clinical advanced BCs, including 5 primary, 14 locally
recurrent, and 144 metastatic BCs. Immunohistochemistry (IHC) with anti–MMR proteins
or next generation sequencing (NGS) to detect microsatellite instability was performed
to evaluate MMR status. The relationship between MMR status and clinicopathologic
characteristics was evaluated.
Results
Among 163 advanced BCs, 19 were hormone receptor (HR)-positive (≥ 10%)/HER2-negative,
17 were HER2+, and 127 were TNBCs/low HR-positive (< 10%). MMR status was evaluated
by IHC in 131 cases and by NGS in 32 cases. Among all cases, only 1 case (0.6%) showed
MMR deficiency. The case with MMR deficiency showed loss of MLH1 and PMS2 proteins,
but no hypermethylation of MLH1 promoter. Sequencing analysis revealed MLH1 genetic alteration with a splice site mutation (208-1G > A), which results in disruption
of the N-terminal ATPase-containing domain (amino acids 25-336). All 127 TNBCs/low
HR-positive BCs showed preserved MMR. PD-L1 (SP142) testing was performed in 66 cases
with 18 (27%) as positive and 48 (73%) as negative, and its expression showed no correlation
with MMR status.
Conclusion
MMR deficiency exists in an extremely low percentage of breast carcinomas, including
TNBCs, suggesting a routine MMR testing to screen BC patients for immunotherapy may
not be cost effective.
Key words
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Article Info
Publication History
Published online: January 21, 2022
Accepted:
January 18,
2022
Received:
November 26,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
