The RAD51 biomarker may help to tailor treatment strategies in patients with early breast cancer, according to a recent study published by Villacampa et al in Clinical Cancer Research.
Background
“A key objective of research focused on early-stage breast cancer is to identify biomarkers that can select patients who might benefit from less aggressive treatments than chemotherapy and personalize therapeutic strategies,” explained senior study author Violeta Serra, PhD, Head of the Vall d’Hebron Institute of Oncology’s Experimental Therapeutics Group.
Study Methods and Results
A novel test based on the detection of the RAD51 protein as a functional biomarker of homologous recombination repair is currently being validated in the stratification of patients with cancer associated with deficiency in this DNA damage repair pathway. The researchers evaluated the feasibility and capacity of the RAD51 test to predict which patients with early-stage breast cancer might respond to neoadjuvant therapy. They analyzed tumor samples from the randomized GeparOla clinical trial that compared pathologic complete response rates with neoadjuvant therapy with PARP inhibitor olaparib vs treatment with carboplatin chemotherapy.
“The GeparOla trial included patients with early HER2-negative breast cancer who had homologous recombination deficiency. In this post hoc analysis, we evaluated if the RAD51 test could identify patients with different responses to neoadjuvant therapy in this preselected patient population,” noted co–lead study author Guillermo Villacampa, PhD, Head of the Vall d’Hebron Institute of Oncology’s Biostatistics Group. “Of the 90 samples evaluable for RAD51 testing, 80% presented RAD51 protein levels correlating with functional [homologous recombination deficiency]. The [pathologic complete response rate] rate in patients treated with the PARP inhibitor who had [homologous recombination deficiency] by RAD51 was 66.7%. This decreased to 22.2% in patients without [homologous recombination deficiency] by RAD51. The multivariable analysis, including clinicopathologic factors, presence of tumor-infiltrating lymphocytes, and type of treatment, demonstrated that RAD51 maintained its prognostic capacity by showing a statistically significant association with [pathologic complete response],” he revealed.
Conclusions
“These findings support the potential of the RAD51 test in tailoring treatment strategies in early-stage breast cancer,” underscored Dr. Serra.
“Future biomarker-driven studies, such as the RADIOLA study led by SOLTI—which has been designed to validate RAD51 in advanced breast cancer, results of which are expected later this year—should consider this present data to refine stratification factors and improve patient selection,” concluded co–study author Judith Balmaña, MD, PhD, Head of the Vall d’Hebron Institute of Oncology’s Hereditary Cancer Genetics Group.
Disclosure: The research in this study was funded by ERA-NET Cofund (Era PerMed), Instituto de Salud Carlos III (ISCIII), the European Union, and the Asociación Española Contra el Cáncer (AECC). For full disclosures of the study authors, visit aacrjournals.org.
