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<p>Advances in breast cancer (BC) therapy are limited by the absence of well-established biomarkers for DNA-damage targeted treatments. We evaluated the predictive and prognostic value of homologous recombination repair (HRR) deficiency (HRD) by RAD51 nuclear foci and stromal tumour-infiltrating lymphocytes (TILs) in early-stage BC patients with suspected germline susceptibility. Among 291 patients, HRD by RAD51 was found in 78.4% of tumours, and 69.8% had low TILs (&lt;30%). In 178 patients treated with neoadjuvant chemotherapy, pathologic complete response (pCR) was higher in those with HRD vs HRR-proficient (HRP) tumours (52.3% vs 36.4%); RAD51 remained independently associated with pCR (<i>p</i> = 0.03). Overall survival (OS) favoured HRD, with 5-year OS of 89.2% vs 82.8% in HRP (<i>p</i> = 0.009), with stronger evidence in triple-negative TILs-low disease (<i>p</i> = 0.005). These findings support RAD51-based HRD assessment as a predictive and prognostic biomarker that may guide treatment decisions in early-stage BC.</p>

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RAD51-based homologous recombination deficiency is associated with treatment response and survival in early breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月5日

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  • Alba Llop-Guevara,
  • Benedetta Pellegrino,
  • Isabel Pimentel,
  • Guillermo Villacampa,
  • Cinzia Solinas,
  • Sara Torres-Esquius,
  • Nicoletta Campanini,
  • Sara Simonetti,
  • Chiara Tommasi,
  • Olga Serra,
  • Matilde Corianò,
  • Daniela Boggiani,
  • Maria Michiara,
  • Roberta Minari,
  • Beatrice Bortesi,
  • Elena Rapacchi,
  • Maria Vittoria Dieci,
  • Matteo Lambertini,
  • Gabriele Zoppoli,
  • Alessio Schirone,
  • Chiara Casarini,
  • Elisabetta Cretella,
  • Laura Cortesi,
  • Enrico Maria Silini,
  • Cristina Saura,
  • Karen Willard-Gallo,
  • Anais Boisson,
  • Antonino Musolino,
  • Violeta Serra,
  • Judith Balmaña,
  • Cristina Cruz

摘要

Advances in breast cancer (BC) therapy are limited by the absence of well-established biomarkers for DNA-damage targeted treatments. We evaluated the predictive and prognostic value of homologous recombination repair (HRR) deficiency (HRD) by RAD51 nuclear foci and stromal tumour-infiltrating lymphocytes (TILs) in early-stage BC patients with suspected germline susceptibility. Among 291 patients, HRD by RAD51 was found in 78.4% of tumours, and 69.8% had low TILs (<30%). In 178 patients treated with neoadjuvant chemotherapy, pathologic complete response (pCR) was higher in those with HRD vs HRR-proficient (HRP) tumours (52.3% vs 36.4%); RAD51 remained independently associated with pCR (p = 0.03). Overall survival (OS) favoured HRD, with 5-year OS of 89.2% vs 82.8% in HRP (p = 0.009), with stronger evidence in triple-negative TILs-low disease (p = 0.005). These findings support RAD51-based HRD assessment as a predictive and prognostic biomarker that may guide treatment decisions in early-stage BC.