Recent Updates for Biomarker Testing in Breast Cancer

EP: 1.The Overall Breast Cancer Landscape

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EP: 2.Recent Updates for Biomarker Testing in Breast Cancer

EP: 3.The Role of Ki-67 and ctDNA as Prognostic or Predictive Markers in Breast Cancer

EP: 4.CDK4/6 & PARP Inhibitors for Early-Stage Breast Cancer

EP: 5.Evolving Treatment Landscape for HER2+ Breast Cancer

EP: 6.Key Updates in Metastatic HER2+ Breast Cancer

EP: 7.Treatment Landscape for Triple-Negative Breast Cancer

EP: 8.Emerging Therapies and Ongoing Trials in Breast Cancer

EP: 9.Clinical Pearls for the Treatment of Breast Cancer

EP: 10.Personalized Treatment Sequencing Is a New Way of Thinking in Breast Cancer

This is a synopsis of an OncView series featuring Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute.

Sara M. Tolaney, MD, MPH, Chief of Breast Oncology at Dana-Farber Cancer Institute, discussed the importance of understanding individual biomarkers to help personalize therapy for breast cancer patients.

For early-stage disease, testing for estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status is standard. However, additional biomarker analyses, especially germline BRCA testing, are important in metastatic disease to guide treatment decisions. HER2-low status, indicating low HER2 expression between HER2-negative and -positive thresholds, should also be assessed, as it has implications for certain targeted therapy options.

In metastatic triple negative breast cancer (TNBC), Dr. Tolaney recommended PD-L1 testing using the 22C3 immunohistochemistry assay, with cancers scoring ≥10 on the combined positive score considered PD-L1 positive. First-line chemotherapy plus immunotherapy is preferred for PD-L1 positive TNBC, given an associated survival benefit.

For ER-positive metastatic disease, Dr. Tolaney advised genomic profiling to detect PIK3CA mutations and ESR1 mutations. After progressing on initial endocrine therapy plus a CDK4/6 inhibitor, the presence of these mutations can guide subsequent therapy choices. PIK3CA mutations indicate potential benefit from alpha-specific PI3-kinase inhibitors like alpelisib. ESR1 mutations may warrant switching to oral selective estrogen receptor degraders like elacestrant. A recent Phase 3 trial showed improved progression-free survival for elacestrant over standard endocrine options in this population. The investigational AKT inhibitor capivasertib also showed promise for PIK3CA- and PTEN-altered ER-positive breast cancer in combination with fulvestrant.

Other biomarkers that may impact treatment decisions include: high tumor mutation burden, which confers eligibility for the immune checkpoint inhibitor pembrolizumab across cancer types; NTRK alterations indicating possible benefit from TRK inhibitors like larotrectinib or entrectinib; and microsatellite instability-high status, also associated with pembrolizumab activity.

In conclusion, Dr. Tolaney emphasized comprehensive genomic and biomarker analyses, especially in metastatic breast cancer, to enable personalized therapy based on an individual patient’s genomic alterations and the growing availability of targeted agents. This more precise approach seeks to improve outcomes while avoiding overtreatment.

*Video synopsis is AI-generated and reviewed by Cancer Network editorial staff.