Real-World Treatment Patterns, Outcomes of Patients With HER2-Low Metastatic Breast Cancer
According to results of a retrospective study, most patients with hormone receptor (HR)-positive, HER2-low metastatic breast cancer switched to chemotherapy after 2 lines of therapy, with a median real-world progression-free survival (PFS) of shorter than 10 months.
According to the study authors, as patients with HER2-low breast cancer (defined as having a score of 1+ or 2+ with immunohistochemical-based analysis of HER2 protein levels and a lack of HER2 gene amplification via in situ hybridization-based assay) “generally have a less favorable prognosis as compared to those with HER2-positive disease who are treated with HER2 targeted treatment,” understanding patient characteristics, current treatment patterns, and clinical outcomes of these patients in the real-world setting is “paramount in the development of innovative, effective therapies."
A retrospective, observational medical chart review cohort study included 444 patients with HR-positive/HER2-low (n = 223), HR-negative/HER2-low, and HER2 immunohistochemical 0 (HER2 null) metastatic breast cancer. Patients within the HR-positive/HER2-low cohort were classified by treatment received, including chemotherapy as first-line therapy for metastatic disease (first-line chemotherapy group, n = 45) and chemotherapy following a hormonal therapy-based regimen (chemotherapy after hormonal therapy group, n = 178). The focus of this analysis is a subgroup comparison of these 2 classifications of the HR-positive/HER2-low cohort.
Among patients in the first-line chemotherapy group, 91.1% received chemotherapy alone in the first line and 8.9% received chemotherapy plus hormonal therapy. Of the patients who received chemotherapy alone, 61.0% received CDK4/6-targeted therapy plus hormonal therapy in the second line, 24.4% received chemotherapy in the second line, and 14.6% received hormonal therapy in the second line. Third-line regimens included hormonal therapy, chemotherapy, CDK4/6-targeted therapy with hormonal therapy, and other targeted agents with or without hormone therapy.
Among the patients in the chemotherapy after hormonal therapy group, 74.7% received CDK4/6-targeted therapy and hormonal therapy in the first line, 20.2% received hormonal therapy alone in the first line, and 5.1% received CDK4/6-targeted therapy alone in the first line. There were 28.7% of these patients who received chemotherapy in the second line, 66.9% in the third line, and 4.5% in the fourth line. The most frequently utilized chemotherapy regimen in the first line was paclitaxel and in the second-line was orally administered capecitabine.
The real-world PFS was 9.3 months among the first-line chemotherapy group vs 8.8 months for the chemotherapy after hormonal therapy group (P = .26). The median times to treated discontinuation were 6.7 months and 8.3 months respectively (P = .13) The difference between subgroups was not statistically significant for either of these outcomes.
Study authors concluded, “The findings highlight the need for more effective therapy post–endocrine-based regimens in this setting.” They added that new treatment options such as trastuzumab deruxtecan “may be more effective for certain patients with disease that progressed following [hormonal therapy]-based regimens” and that “future research may identify interactions between hormone receptors and HER2 receptors that provide insight into mechanisms of treatment resistance” in this population.
Source:
Mehta S, Kwong J, Lam C, and Feinberg B. Real-world treatment patterns and outcomes of patients with hormone receptor-positive/HER2-low metastatic breast cancer treated with chemotherapy. Oncologist. 2025;30(6). doi:10.1093/oncolo/oyaf106
