Dr Kalinsky on Multidisciplinary Considerations for ESR1+ Breast Cancer Care

“As [the paradigm] continues to shift, the SERENA-6 [regimen] may be, for some patients, a paradigm shift as a way of making decisions based upon a targetable mutation.”

Kevin Kalinsky, MD, MS, FASCO, professor and director in the Division of Medical Oncology in the Department of Hematology and Medical Oncology at the Emory University School of Medicine; as well as the Louisa and Rand Glenn Family Chair in Breast Cancer Research and the director of the Glenn Family Breast Center at the Winship Cancer Institute of Emory University, discussed the focus of a molecular tumor board discussion presented at the 43rd Annual Miami Breast Cancer Conference.

The panel, which featured a diverse range of specialists—including medical oncologists, surgeons, and radiation oncologists—convened to evaluate complex breast cancer cases through the lens of precision medicine. Kalinsky noted that these multidisciplinary discussions are essential for navigating the rapidly shifting paradigms of metastatic breast oncology, where genomic data are increasingly dictating clinical pathways.

A significant portion of the dialogue focused on the management of hormone receptor–positive, HER2-negative metastatic breast cancer, specifically in the context of the phase 3 SERENA-6 trial (NCT04964934) paradigm. Notably, SERENA-6 showed the benefit of adding camizestrant to continued therapy with a CDK4/6 inhibitor compared with continuing a CDK4/6 inhibitor with an aromatase inhibitor upon ESR1 mutation detection before radiographic disease progression on first-line therapy in this population of patients.

Kalinsky explained the ongoing debate regarding patients currently undergoing first-line therapy with a combination of an aromatase inhibitor and a CDK4/6 inhibitor. The central question facing the multidisciplinary team in the tumor board discussion was the clinical utility of proactively screening for ESR1 mutations. According to Kalinsky, the board explored the potential benefits of switching to camizestrant, an oral selective estrogen receptor degrader (SERD), and continuing the CDK4/6 inhibitor upon the detection of a mutation. This switch would occur even in the absence of radiographic evidence of disease progression.

The discussion further extended to the clinical significance of other targetable genomic alterations, including somatic PALB2 and ERBB2 mutations. Kalinsky emphasized that the primary objective of these molecular tumor boards is to contextualize such genomic findings within the broader clinical presentation of metastatic disease. He asserted that the ability to target specific tumor alterations has become increasingly refined, supported by the development of therapeutic agents that offer improved tolerability for patients. This precision allows for a more nuanced understanding of tumor biology, ensuring that treatments are tailored to individual molecular profiles, he stated.

Ultimately, Kalinsky concluded that the management of metastatic breast cancer is moving away from a one-size-fits-all methodology. He highlighted that the integration of genomic findings into clinical practice provides multiple avenues for evaluating tumor behavior and individualizing patient care.