RAD51-based homologous recombination deficiency is associated with treatment response and survival in early breast cancer
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.
Authors
- Alessio Schirone
- Enrico Maria Silini (ORCID: https://orcid.org/0000-0003-2578-3059)
- Violeta Serra
- Chiara Casarini
- Elisabetta Cretella (ORCID: https://orcid.org/0000-0001-8491-3058)
- Benedetta Giovanna Pellegrino
- Roberta Minari (ORCID: https://orcid.org/0000-0002-4808-0308)
- Matilde Coriano
- Anaïs Boisson
- Chiara Tommasi (ORCID: https://orcid.org/0000-0002-9230-9288)
- Sara Simonetti (ORCID: https://orcid.org/0000-0003-2406-030X)
- Daniela Boggiani
- Nicoletta Campanini (ORCID: https://orcid.org/0009-0006-7259-5869)
- Alba Llop‐Guevara (ORCID: https://orcid.org/0000-0002-7913-9472)
- I. Pimentel
- Elena Rapacchi
- Maria Vittoria Dieci (ORCID: https://orcid.org/0000-0002-3967-9861)
- Beatrice Bortesi
- Judith Balmaña
- C. Solinas
- Olga Serra (ORCID: https://orcid.org/0009-0003-6282-5809)
- K. Willard-Gallo
- Cristina Cruz
- G. Villacampa
- M. Lambertini
- Gabriele Zoppoli
- Antonino Musolino
- Laura Cortesi
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- University of Modena and Reggio Emilia (IT)
- Universitat Autònoma de Barcelona (ES)
- University of Parma (IT)
- Université Libre de Bruxelles (BE)
- University of Cagliari (IT)
- Institut Jules Bordet (BE)
- Azienda Unita' Sanitaria Locale Di Modena (IT)
- Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
- Ospedale di Bolzano (IT)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Vall d'Hebron Institut de Recerca (ES)
- Istituto Oncologico Veneto (IT)
- Arcispedale Sant'Anna (IT)
- Ospedale Policlinico San Martino (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Institut Català de la Salut (ES)
- Vall d'Hebron Institute of Oncology (ES)
- University of Bologna (IT)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2026-03-05
- DOI
- https://doi.org/10.1038/s41523-026-00920-5
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundación Cellex
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación