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<p>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 <i>p</i> = 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; <i>p</i> = 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; <i>p</i> = 0.008) and OS (HR 0.30; 95% CI 0.12–0.81; <i>p</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月29日

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  • Eriseld Krasniqi,
  • Anna Di Benedetto,
  • Lorena Filomeno,
  • Teresa Arcuri,
  • Cristiana Ercolani,
  • Gianluigi Ferretti,
  • Simona Gasparro,
  • Alberto Fulvi,
  • Arianna Roselli,
  • Loretta D’Onofrio,
  • Laura Pizzuti,
  • Maddalena Barba,
  • Marcello Maugeri-Saccà,
  • Claudio Botti,
  • Franco Graziano,
  • Ilaria Puccica,
  • Sonia Cappelli,
  • Fabio Pelle,
  • Flavia Cavicchi,
  • Amedeo Villanucci,
  • Ida Paris,
  • Tatiana D’Angelo,
  • Fabio Calabrò,
  • Sandra Rea,
  • Roy De Vita,
  • Letizia Perracchio,
  • Giuseppe Sanguineti,
  • Silvia Takanen,
  • Laura Marucci,
  • Lucia Goanta,
  • Laura Greco,
  • Ramy Kayal,
  • Pina Tiziana Falbo,
  • Paola Scavina,
  • Matteo Vergati,
  • Marco Mazzotta,
  • Nicola Calonaci,
  • Mauro Minelli,
  • Giuliana D’Auria,
  • Giulio Caravagna,
  • Giovanni Blandino,
  • Patrizia Vici

摘要

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.