Dr Cobain on Endocrine Therapy–Based Treatment Strategies in HR+/HER2– Breast Cancer

Erin Frances Cobain, MD, medical oncologist, co-director, Breast Cancer Clinical Research Team, Rogel Cancer Center, University of Michigan, discusses optimal endocrine therapy–based treatment strategies in the second- and third-line settings after disease progression on first-line endocrine therapy plus a CDK4/6 inhibitor in patients with hormone receptor–positive, HER2-negative metastatic breast cancer.

When patients progress on initial endocrine therapy combined with a CDK4/6 inhibitor, one of the critical initial considerations is the type of endocrine therapy used in the first-line setting—specifically, whether an aromatase inhibitor (AI) or fulvestrant (Faslodex) was administered, Cobain begins. The choice between these options can impact subsequent treatment decisions, Cobain notes.

Another key aspect to address is the molecular profile of the tumor, as understanding the tumor's molecular features and identifying targetable genomic alterations is crucial, according to Cobain. This involves timing molecular testing appropriately, she continues. Certain mutations, such as activating alterations in PI3K, are often present at the time of metastatic disease diagnosis and can be detected from primary tumor samples. These alterations are considered tumor-initiating events and tend to be detectable throughout the disease course, Cobain elucidates.

However, activating ESR1 mutations may not be evident in initial molecular testing if performed early in the disease course, such as at the time of metastatic disease diagnosis before prolonged AI exposure, she adds. Therefore, if a patient has undergone several years of AI therapy, it becomes essential to repeat molecular testing before deciding on second-line treatment to identify emerging ESR1 mutations or other actionable molecular targets, she explains. Serial tissue sampling can be challenging, which highlights the value of liquid biopsies or circulating tumor DNA assays that are now more accessible, Cobain notes.

These noninvasive testing methods provide an alternative to tissue-based biopsies when repeat tissue sampling is difficult or impractical for patients, enabling oncologists to make informed treatment decisions based on the latest molecular insights, Cobain says. Liquid biopsies are increasingly integrated into clinical practice to optimize personalized treatment strategies for patients with advanced breast cancer, she concludes.