What does this research mean for the field?

In patients with triple-negative breast cancer receiving platinum-based neoadjuvant chemotherapy, germline homologous recombination deficiency (HRD) independently predicts pathological complete response, whereas baseline tumor phospho-DDR activation does not. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to determine the predictive value of DNA damage response biomarkers for pathological complete response in triple-negative breast cancer patients receiving chemotherapy.

June 1, 2026npj Breast Cancer0 citationsOpen Access

Platinum-based neoadjuvant chemotherapy and the predictive role of DNA damage response biomarkers in TNBC: the NeoCarbo study

EKEriseld Krasniqi ABAnna Di Benedetto LFLorena Filomeno

Key Points

This study aims to determine the predictive value of DNA damage response biomarkers for pathological complete response in triple-negative breast cancer patients receiving chemotherapy.
Multicenter trial involving stage I-III TNBC patients receiving carboplatin and weekly paclitaxel, followed by epirubicin/cyclophosphamide and surgery.
Assessment of germline homologous recombination deficiency and DNA damage response activation as predictive biomarkers for pathological complete response.
Primary endpoint was pathological complete response; secondary endpoints included disease-free survival and overall survival.
Pathological complete response was achieved in 77 out of 128 patients (60.2%; 95% CI 51.1-68.7%).
In patients with complete biomarker data, HRD positivity predicted a higher pCR rate of 78.6% compared to 57.7% in HRD-negative subjects (p=0.086).
At median follow-up of 60.4 months, pCR was linked to improved disease-free survival (HR 0.29; p=0.008) and overall survival (HR 0.30; p=0.017).

Abstract

Platinum-containing neoadjuvant chemotherapy increases pathological complete response (pCR) rates in triple-negative breast cancer (TNBC), but predictive biomarkers remain incompletely defined. In the multicenter NeoCarbo cohort, we assessed a carboplatin-containing neoadjuvant regimen and examined whether germline homologous recombination deficiency (HRD) and baseline tumor DNA damage response (DDR) activation predict pCR and outcomes. Stage I-III TNBC patients at three centers received carboplatin (AUC6 q3w×4) plus weekly paclitaxel (×12), followed by dose-dense epirubicin/cyclophosphamide (q2w×4) and surgery. The primary endpoint was pCR (ypT0/is ypN0); secondary endpoints were disease-free survival (DFS) and overall survival (OS). Germline HRD was defined by pathogenic/likely pathogenic variants in BRCA1/2 and other homologous recombination genes, and DDR activation was assessed centrally by phospho-DDR immunohistochemistry. Among 128 patients, pCR occurred in 77 (60.2%; 95% CI 51.1-68.7%). HRD status was available in 80 patients (28 HRD-positive), with pCR rates of 78.6% in HRD-positive versus 57.7% in HRD-negative tumors (Fisher p = 0.086). In a bivariable analysis restricted to patients with complete biomarker data, HRD positivity independently predicted pCR (adjusted OR 2.68; 95% CI 1.16-6.85; p = 0.027), whereas DDR tertiles were not independently associated with pCR. At a median follow-up of 60.4 months, pCR was associated with improved DFS (HR 0.29; 95% CI 0.12-0.72; p = 0.008) and OS (HR 0.30; 95% CI 0.12-0.81; p = 0.017). Grade ≥3 toxicity occurred in 14.4% during carboplatin-paclitaxel and 18.9% during epirubicin-cyclophosphamide, predominantly hematologic. These findings support high pCR rates with this regimen and suggest that HRD may identify patients more likely to achieve pCR, whereas baseline tumor phospho-DDR lacked predictive value; future evaluation may require dynamic DDR assessment in larger studies.

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