139 Real-World Biomarker Testing in HR+/HER2- Metastatic Breast Cancer

Background

CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) is the standard of care for first-line treatment of patients with hormone receptor–positive, HER2-negative (HR+/HER2–) metastatic breast cancer. Recently approved biomarker-driven therapies provide new opportunities for targeted second-line treatment for these patients. Unfortunately, timely biomarker testing has been low (<40%, depending on the biomarker), which impacts treatment decisions and outcomes. This study describes contemporary biomarker testing patterns in a novel multi-institutional, patient-consented cohort.

Methods

We conducted a retrospective cohort study using the Outcomes4Me database of processed longitudinal medical records data. The database includes more than 7700 patients with cancer in the US seen at more than 3500 clinical sites, including community and academic practice types. Patients eligible for this cohort were 18 years or older and diagnosed with HR+/HER2– metastatic breast cancer between January 2018 and October 31, 2024.

Demographics, clinical characteristics, and biomarker testing rates (PIK3CA, ESR1, AKT1, PTEN, BRCA1/2) were summarized with descriptive statistics. Biomarker testing was evaluated against sociodemographic characteristics (practice type, patient age) using covariate adjusted analysis.

Results

A total of 288 patients were included in this analysis: 98% female, 68% treated in community practices, 46% progressed to second-line therapy, and 50% on first-line therapy at end of study period. Median age at metastatic breast cancer diagnosis was 58 (IQR 47-66), with 8% under age 40 and 27% aged 65 or older. Median follow-up was 18 months (IQR 10-33). A total of 85% of patients received first-line ET plus CDK4/6 inhibitor treatment, with first-line median time to next treatment of 23 months, and median time to chemotherapy of 49 months.

Testing of clinically actionable biomarkers was low, ranging from 17.4% (AKT1) to 27.4% (PIK3CA) on or after first-line initiation, with no significant differences between community and academic settings. Testing was not associated with key clinical milestones, including metastatic diagnosis (9-17% testing rate), at first-line progression (6%-11%), or during/after subsequent lines of therapy (6%-15%).

For patients who progressed to second-line treatment, ESR1, PIK3CA, and BRCA2 testing rates were higher than in first-line and were significantly higher (P <.05) in the community vs academic setting (Table). ESR1 and BRCA2 testing rates, for those who advanced to second-line treatment, were significantly higher in patients younger than 40 years old at metastatic breast cancer diagnosis than in older patients.

Conclusions

In this contemporary patient cohort, biomarker testing was low and not aligned with the timing of second-line treatment decisions. Low biomarker testing rates continue to represent missed opportunities for identifying tumor-directed targeted therapies and improving outcomes.