Understanding Treatment Options for ER+/HER2–, ESR1-Mutant Metastatic Breast Cancer

In this on-demand webinar series, Dr. Igor Makhlin discusses personalized treatment options for patients with estrogen receptor–positive, HER2-negative metastatic breast cancer, including the role of ESR1 mutation testing and targeted therapies, such as Orserdu (elacestrant).

This patient-focused overview provides essential information for those diagnosed with ER-positive, HER2-negative metastatic breast cancer, along with their caregivers. Makhlin highlights the importance of understanding tumor mutations, testing methods, and evolving treatment strategies, including Orserdu.

ER-positive metastatic breast cancer relies on estrogen to fuel tumor growth. Endocrine therapies, such as aromatase inhibitors and CDK4/6 inhibitors, are typically used as first-line treatments to block estrogen production and slow disease progression. However, resistance may develop, especially in the presence of mutations like ESR1, which can cause therapies to become less effective over time.

To personalize treatment, biomarker testing—including blood tests—helps identify actionable mutations such as ESR1. If an ESR1 mutation is detected following disease progression, targeted therapies, such as Orserdu, become viable options. Orserdu is the first oral medication specifically approved for patients with ER-positive, HER2-positive, metastatic breast cancer with ESR1 mutations following prior endocrine therapy. It offers a convenient daily pill form and has demonstrated effectiveness in clinical trials, including in the phase 3 EMERALD study (NCT03778931), which enrolled patients with ESR1 mutations.

Monitoring through regular blood tests is crucial for tracking mutation development and disease progression. If resistance mutations are identified, providers may recommend other targeted therapies, including PI3K inhibitors like alpelisib, in the presence of PIK3CA mutations.

In conclusion, Makhlin explains that personalized treatment for patients with ER-positive/HER2-negative metastatic breast cancer involves understanding tumor genetics, timely testing, and appropriate use of targeted agents like elacestrant. Keeping communication open with your healthcare team ensures active management and adaptation of treatment strategies, empowering patients and caregivers to stay informed and in control of their cancer journey.