Optimizing Treatment Strategies for HR+/HER2- Breast Cancer: ESR1 Mutations and Emerging Therapies

Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, explore the clinical significance of *ESR1* mutations in HR+/HER2- metastatic breast cancer patients, including their impact on disease prognosis, treatment outcomes, and the increasing prevalence of these mutations with each line of endocrine therapy, ultimately informing their therapeutic approach.

The key opinion leaders (KOLs) review the current testing methods for detecting ESR1 mutations and explore the existing strategies employed to overcome or delay the development of these mutations and the associated endocrine resistance in patients with HR+/HER2- metastatic breast cancer.

In their discussion, medical experts in the field of breast cancer explore the role of liquid biopsies and compare the significance of ESR1 mutations to other biomarkers, such as PIK3CA, in terms of their driver versus passenger status in the context of HR+/HER2- breast cancer.

Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, present a patient case involving a 54-year-old postmenopausal woman diagnosed with a 2.1cm estrogen receptor positive (ER+), HER2 negative breast cancer, and discuss the clinical implications and management strategies for this specific patient scenario.

Key opinion leaders examine the EMERALD trial, which evaluates the efficacy of elacestrant in patients with HR+ HER2- metastatic breast cancer, focusing on the subgroup analysis of patients with visceral metastases, and explore how the trial's design and results have influenced their clinical practice.

The breast cancer experts share their clinical experiences and strategies regarding the optimal timing for testing ESR1 mutations in patients with HR+/HER2- metastatic breast cancer, elaborating on how the specific points in the treatment journey at which they recommend testing influence their subsequent treatment decisions and overall approach to patient management.

Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, discuss the clinical presentation and management of a 64-year-old postmenopausal female with a history of rheumatoid arthritis who was diagnosed with stage IV, grade 3, invasive ductal carcinoma in her left breast, taking into account her comorbidities and the advanced stage of her breast cancer.

In their discussion, the key opinion leaders explore the significance of PIK3CA mutations in HR+/HER2- metastatic breast cancer and review the findings from two pivotal clinical trials, SOLAR-1 and CAPItello-291, which investigated the efficacy of targeted therapies in patients harboring these mutations.

The expert panel examines the subgroup data from the postMONARCH study, focusing on patients with ESR1 and PIK3CA mutations, and emphasizes the important role of CDK4/6 inhibitors in the treatment of these specific patient populations with HR+/HER2- metastatic breast cancer.

In their discussion, the key opinion leaders explore the potential of combination therapies in HR+/HER2- metastatic breast cancer, with a specific focus on the ELECTRA study, which investigated the combination of elacestrant and abemaciclib.

The key opinion leaders discuss the current unmet needs in the management of HR+/HER2- metastatic breast cancer and explore potential future directions and strategies that may lead to improved patient outcomes.

In their concluding remarks, Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, summarize their key insights and perspectives on the management of HR+ breast cancer.