# BRCA2 Reversion Mutation after Neoadjuvant Dose-Dense EC and Dose-Dense Paclitaxel in Triple-Negative Breast Cancer: A Case Report and Literature Review

## TL;DR

A patient with BRCA2-mutated breast cancer developed a reversion mutation after chemotherapy, leading to early recurrence, suggesting the need for monitoring BRCA status.

## Contribution

Reports a rare case of BRCA2 reversion mutation emerging without PARPi or platinum therapy, highlighting its clinical implications.

## Key findings

- BRCA2 reversion mutation was detected in residual tumor after chemotherapy, restoring the open reading frame.
- The patient experienced early systemic recurrence, including leptomeningeal metastasis, 7 months post-surgery.
- The case suggests reversion mutations can occur early, independent of PARPi or platinum exposure.

## Abstract

BRCA reversion mutations are known mechanisms of acquired resistance to poly (ADP-ribose) polymerase inhibitors (PARPis) and platinum agents. However, their clinical emergence without such therapies is rarely reported.

We describe a 44-year-old woman with early-stage triple-negative breast cancer carrying a germline BRCA2 mutation who developed a BRCA2 reversion mutation after neoadjuvant dose-dense epirubicin and cyclophosphamide (EC) followed by dose-dense paclitaxel, without prior PARPi or platinum exposure. She underwent modified radical mastectomy and achieved a good pathological response; however, she developed early systemic recurrence, including leptomeningeal metastasis, 7 months postoperatively. Comprehensive genomic profiling of the residual breast tumor revealed a BRCA2 reversion mutation (allele frequency: 6.7%) that restored the open reading frame. We speculate that the genomic instability in the tumor may have induced a spontaneous reversion mutation early in the disease course.

This case suggests that a BRCA2 reversion mutation can arise early, even before PARPi or platinum exposure. Serial monitoring of BRCA status may help predict therapeutic resistance in patients with germline BRCA-mutated breast cancer.