Navigating Treatment/Testing Decisions in Metastatic HR+/HER2– Breast Cancer

The treatment landscape for metastatic hormone receptor (HR)–positive, HER2-negative breast cancer continues to evolve, demanding nuanced clinical decision-making. Although endocrine therapy remains the cornerstone of initial management, the emergence of antibody-drug conjugates (ADCs) such as fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and sacituzumab govitecan-hziy (Trodelvy) offers promising avenues for patients experiencing disease progression.

In a recent interview with CancerNetwork®, Kit Yu Lu, MD, an oncology/hematology oncologist who specializes in breast cancer at the University of Pittsburgh Medical Center, shared valuable insights into identifying specific patient characteristics and disease progression patterns that might warrant earlier consideration of T-DXd or sacituzumab govitecan in this setting.

Lu specifically addressed the role of sacituzumab govitecan, with a clear scenario for its application in the HR-positive/HER2-negative metastatic setting. This treatment can be used for patients who have demonstrated progression through prior lines of therapy encompassing endocrine-based treatments, any relevant targeted therapies, and 1 to 2 lines of standard chemotherapy. This represents a population where sacituzumab govitecan warrants serious consideration. This recommendation underscores the importance of recognizing the limitations of conventional therapies in patients who are heavily pretreated and proactively exploring alternative strategies with distinct mechanisms of action.

Beyond treatment sequencing, the increasing utilization of liquid biopsies in oncology raises critical questions regarding the interpretation and clinical significance of detected somatic mutations. Lu offered her perspective on the specific context of somatic BRCA mutations identified through this less invasive approach in patients with HR-positive/HER2-negative metastatic breast cancer. Although the established utility of PARP inhibitors is largely predicated on the presence of germline BRCA mutations, the implications of somatic alterations remain less clear.

Currently, there are limited data available to guide the use of PARP inhibitors in the setting of somatic BRCA mutations, Lu mentioned. Drawing upon findings from smaller studies that have suggested some level of effectiveness, she emphasized that the small amount of evidence supporting PARP inhibitor efficacy primarily stems from research involving germline mutations.

Transcript:

For our patients with HR-positive, HER2-negative metastatic breast cancer, I would consider sacituzumab govitecan appropriate for those who have progressed through their endocrine therapy, targeted therapy, and 1 to 2 lines of standard chemotherapy.

There are limited data regarding the use of the PARP inhibitors in somatic BRCA mutations. In smaller studies, there has been some effectiveness in using PARP inhibitors, but most of our data are on germline mutations. I typically recommend discussing the risks and benefits with patients and following our standard guidelines in regard to PARP inhibitor use in the context of clinical trials.