New Genetic Signatures May Help Identify Triple-Negative Breast Cancer Patients Who Respond to Cisplatin

A team of researchers has identified that nucleotide excision repair (NER) deficiency, as detected by specific mutational signatures, is linked to how triple-negative breast cancer (TNBC) responds to platinum-based chemotherapy drugs like cisplatin. While platinum therapies can increase pathological complete response rates compared to standard non-platinum treatments, their toxicity profiles highlight the ongoing need for accurate predictive biomarkers. Current methods heavily rely on testing for homologous recombination deficiency, though approved assays have demonstrated only modest predictive capability in clinical evaluations.

Using data from the Cancer Genome Atlas and clinical trial cohorts, the investigators evaluated the ERCC2mut score—a metric originally developed from bladder cancer studies—alongside other genomic markers. The analysis revealed that approximately 4.7 percent of breast cancer cases showed indications of NER deficiency without overlapping homologous recombination deficiency. In a cohort of cisplatin-treated TNBC patients, both NER and homologous recombination signatures associated with treatment response, yet the two methods largely flagged distinct patient groups. Additional evaluation within a randomized trial further confirmed that NER-associated signatures correlated with cisplatin effectiveness, but showed no such association with paclitaxel.

What to know: These early-stage findings suggest that combining biomarker strategies could capture a wider subset of patients who may benefit from platinum therapies. Because the study relies on genomic sequencing data and retrospective cohort analyses rather than broad prospective trials, these markers are not yet ready to guide immediate treatment choices. Patients should consult their oncologists to discuss personalized treatment plans and the most appropriate testing options available.