Approaches to Mutation Testing for Patients With HR+/HER2-low mBC and ET-Resistant Disease

Author(s):

Laura Spring, MD, and Manali Bhave, MD, discuss considerations for systemic therapy selection in a patient with recurrent hormone receptor-positive, HER2-low breast cancer, including use of plasma and tissue genomic testing and endocrine therapy sequencing based on factors like prior response and ESR1 mutation status.

EP: 1.Clinical Scenario: A 57-Year-Old Woman With Metastatic Breast Cancer

EP: 2.Current First-Line Systemic Therapy Options for HER2+ Metastatic Breast Cancer

EP: 3.Key Clinical Trials in the First-Line Treatment of HER2+ Metastatic Breast Cancer

EP: 4.Standard of Care Regimens for Second-Line Treatment of HER2+ Metastatic Breast Cancer

EP: 5.Sequencing Therapies in the Third-Line and Beyond for Patients With HER2+ Metastatic Breast Cancer

EP: 6.Clinical Scenario: A 65-Year-Old Post-Menopausal Woman With Metastatic Breast Cancer

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EP: 7.Approaches to Mutation Testing for Patients With HR+/HER2-low mBC and ET-Resistant Disease

EP: 8.Factors for Consideration When Choosing Among Options for Patients with ET-resistant ER+/HER2- mBC

EP: 9.Sequencing Antibody-Drug Conjugates (ADCs) in HR+/HER2-Low Metastatic Breast Cancer

EP: 10.Exciting Data in the Treatment of HER2-low from SABCS 2023

Spring and Bhave discuss their approach to obtaining genomic profiling in metastatic HR+/HER2-low breast cancer. Both prefer comprehensive sequencing upfront on metastatic biopsies, even if not immediately actionable, as it can inform future treatment options. For example, knowing PIK3CA mutation status can guide considering alpelisib later, and pre-diabetes can be managed proactively.

Spring often sends ctDNA first for faster results, then decides if tissue testing is needed, acknowledging PIK3CA detection is more sensitive in tissue. At each progression, she typically sends ctDNA and considers tissue sequencing if concerns arise about biology changes.

Bhave agrees plasma testing is preferred for progressing patients as it's quicker and less invasive. However, she rebiopsies in cases of unexpected responses or discordant results to recheck receptor status and rule out changing disease biology. For HER2-0 patients progressing through multiple therapies, she may rebiopsy before considering trastuzumab deruxtecan to confirm some level of HER2 expression.

They emphasize the importance of testing for ESR1 mutations given the recent FDA approval of elacestrant, a novel oral SERD, based on the EMERALD trial. Spring notes the real-world challenge of identifying optimal candidates at varying points in their treatment journey. Bhave highlights a subgroup analysis showing longer PFS with elacestrant in ESR1-mutant patients who responded to prior CDK4/6 inhibition for >12 months, supporting its use post-progression on first-line AI/CDK4/6i in ESR1-mutant cases.

This summary was AI-generated and edited for clarity.