No Link Found Between HRD and Pathologic Response in Triple-Negative Breast Cancer

The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Baseline homologous recombination deficiency (HRD) scores do not predict how patients with triple negative breast cancer will respond to preoperative chemotherapy, according to data from a phase 2 study presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The study authors randomized 140 patients with BRCA1/2-proficient/unknown stage I to stage III triple negative breast cancer to receive 4 cycles of cisplatin 75 mg/m² (72 patients) every 3 weeks or 12 weeks of paclitaxel 80mg/m² (68 patients), prior to surgery. At baseline, the investigators performed homologous recombination deficiency assays on patients’ tissue.

Patients who did not respond to treatment at 12 weeks could crossover to a different chemotherapy regimen. The study’s primary objectives were to detect a positive association of HRD with pathologic response (RCB 0-1) versus not detect a positive association (RCB 2-3) to cisplatin as well as detect a negative association to paclitaxel.

The researchers were able to evaluate 138 of the 140 patients for response at 12 weeks. Analyses performed after enrollment revealed that 8 patients (5.8%) had germline DNA-repair pathway mutations. The results of HRD assays (which were developed by Myriad Genetics) were available for 105 patients and showed that 75 patients were HRD positive. Of these patients 39 were in the cisplatin group, and 36 were in the paclitaxel group. Among the patients who were evaluable for response, 87 (63%) underwent surgery at 12 weeks, and 51 (37.0%) crossed over.

The researchers did not find an association between HRD score and RCB response to either neoadjuvant cisplatin (overall response [OR] 2.78; CI, 0.61-17.74) or paclitaxel (OR, 2.78; CI, 0.61-17.74).

“In conclusion, in this mostly BRCA-proficient triple negative breast cancer cohort, HRD positivity using this HRD assay was not predictive of response to preoperative cisplatin or paclitaxel chemotherapy,” said study author Erica L. Mayer, MD, MPH, a senior physician at the Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

Reference

Mayer EL, Gupta Abramson V, Jankowitz RC, et al. TBCRC 030: A randomized phase II study of preoperative cisplatin versus paclitaxel in TNBC—evaluating the homologous recombination deficiency (HRD) biomarker Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 507.