7 Similarly, in BrighTNess ( Identifier: NCT02032277), those patients with high HRD scores had higher rates of response across all treatment arms, but HRD score did not predict for specific response to carboplatin. A retrospective exploratory analysis suggested that a positive HRD score in patients without known BRCA mutation predicted response to chemotherapy, but not specifically to carboplatin.
#Hrd score trial
For example, the GeparSixto trial ( Identifier: NCT01426880) analyzed carboplatin added to anthracycline/taxane-based neoadjuvant chemotherapy in women with TNBC. However, retrospective studies looking at HRD assay-based scores have failed to confirm that a positive HRD score specifically predicts response to platinum chemotherapy in breast cancer. 3,4,5,6 These studies have resulted in the US Food and Drug Administrations’s (FDA’s) approval of HRD assays for several indications in ovarian cancer. The clinical usefulness of the HRD assay has been defined in several large trials that studied PARP inhibitor use in ovarian cancer. 2 Based on these results, they suggested that this genomic measure - the basis of the HRD assay - could possibly identify patients who would benefit from treatments targeting defective DNA repair in TNBC and other cancer types. In 2012, Dr Silver and colleagues published a paper showing that the number of these abnormalities, chromosomal regions with allelic imbalance extending to the end of the chromosome, could predict sensitivity to cisplatin and pathologic response to preoperative cisplatin in patients with TNBC. “The higher the number of abnormalities, the more likely that cell line was defective in BRCA1 or BRCA2 or the pathway that the BRCA1/2 proteins function in, and the more likely the cell lines were sensitive to platinum,” Dr Silver said. In early experiments, they showed that tumors have certain chromosomal abnormalities that indicate defective DNA repair and the number of these abnormalities predict platinum sensitivity in breast cancer cell lines. Research into HRD was pioneered by Daniel Silver, MD, PhD, associate professor of medical oncology and cancer biology at Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania, and colleagues. “HRD biomarker assays are being studied to see if they can identify BRCA-like cancers and possibly help direct chemotherapy selection for patients, for example, considering agents that target DNA or create DNA damage, like platinum chemotherapy.” DNA Damage Repair Mayer, MD, MPH, assistant professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, Boston, Massachusetts. “Among TNBC that develop in people that do not have germline BRCA1/2 deficiency, there may exist a subset that have a similar phenotype that we might define as ‘BRCA-like’,” explained study author Erica L. A homologous recombination deficiency (HRD) assay testing for impaired double-strand DNA break repair did not predict pathologic response to preoperative chemotherapy in a randomized trial of women with early-stage triple-negative breast cancer (TNBC) and no known BRCA germline mutation, 1 adding to evidence that suggests that HRD score currently has no clinical role in the selection of treatment for women with this breast cancer subtype.