Dr Domchek on the Importance of Germline Testing in Breast Cancer Care

Susan Domchek, MD, FASCO, executive director, the Basser Center for BRCA, director, the MacDonald Women’s Cancer Risk Evaluation Center, the Basser Professor in Oncology at Penn Medicine, discusses the importance of germline testing in breast cancer care.

Over the past decade, the importance of using genetic markers to determine the optimal treatment plan for patients with breast cancer has become more evident, Domchek begins. Additionally, using a genetic markers can have an effect at several stages of treatment. For example, data for the PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) showed that these agents were effective in the treatment of select patients with advanced breast cancer harboring BRCA mutations, Domchek continues, noting that these PARP inhibitors demonstrated improved efficacy over chemotherapy in this setting.

In January 2018, the FDA approved olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy. Additionally, talazoparib was approved by the FDA in October 2018 for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. Olaparib was then approved by FDA in setting in March 2022 for patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who have previously received chemotherapy either before or after surgery.

Patients with early-stage, high-risk breast cancer, including those with positive lymph nodes, triple-negative breast cancer (TNBC) that is more than 2 cm in diameter, or those with breast cancer that has not completely responded to preoperative chemotherapy, can now be candidates for olaparib following the completion of other therapy if they harbor a BRCA1 or BRCA2 mutation. The use of a PARP inhibitor in this setting decreases the chances that the cancer will come back outside of the breast and improve overall survival, Domchek emphasizes.

Based on this knowledge, it is important to recognize individuals who are good candidates for genetic testing, including any individual with TNBC, anyone with breast cancer under the age of 50, or anyone who has a family history of breast cancer, ovarian cancer, metastatic prostate cancer, or pancreatic cancer, Domchek explains. Although other patients are also candidates for genetic testing, these are subgroups where it is always important to have genetic testing done, Domchek concludes.