BRCA2 Reversion Mutation after Neoadjuvant Dose-Dense EC and Dose-Dense Paclitaxel in Triple-Negative Breast Cancer:...

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.