ESMO Breast 2021: Clinical Role of RAD51 Testing in Triple-Negative Breast Cancer
Posted: Tuesday, May 25, 2021
Two studies presented during the European Society for Medical Oncology (ESMO) Breast Cancer Virtual Congress 2021 suggest that testing for the presence of RAD51, a product of homologous recombination repair (HRR), may be useful in clinical decision-making for patients with triple-negative breast cancer. Testing for RAD51 in these breast tumors allowed for assessment of functional HRR, identifying tumors sensitive to PARP inhibition, and predicting the clinical benefit of carboplatin in neoadjuvant therapy. These study findings were presented by Violeta Serra, PhD, and Alba Llop-Guevara, PhD, both of Vall d’Hebron Institute of Oncology, Barcelona (Abstracts 10 and 20).
The study presented by Dr. Serra quantified the percentage of RAD51 foci in the S/G2 phase of the cell cycle using immunofluorescence. Samples from patients with triple-negative breast cancer were assessed at baseline and after treatment with rucaparib. Baseline RAD51 was considered low if less than 10% of cells were positive for RAD51. The RAD51 scores increased from baseline to after treatment, a reflection of rucaparib inducing RAD51-mediated HRR. Tumors with low levels of RAD51 had greater circulating tumor DNA suppression than tumors with high levels of RAD51 after rucaparib therapy, suggesting that RAD51-low tumors appear to be sensitive to PARP inhibitors.
In the study presented by Dr. Llop-Guevara, researchers conducted a blinded analysis of the GeparSixto trial, where 200 patients with triple-negative breast cancer received neoadjuvant paclitaxel, doxorubicin, and bevacizumab with or without carboplatin. Homologous recombination deficiency markers including RAD51, BRCA1, and γH2AX nuclear foci were quantified in 133 of these tumor samples. The RAD51 test was able to identify functional homologous recombination in 93% of the BRCA-mutated tumors and 45% of the non-BRCA mutated tumors. Patients with high levels of RAD51 had similar pathologic complete response rates with quadruplet (paclitaxel, doxorubicin, bevacizumab, carboplatin) or triplet (paclitaxel, doxorubicin, bevacizumab) therapy. However, those with RAD51-low tumors saw a clinical benefit from the addition of carboplatin (pathologic complete response rate 66% vs. 33% without carboplatin, odds ratio = 3.96).
Disclosure: For full disclosures of study authors from both trials, visit oncologypro.esmo.org and oncologypro.esmo.org.