In a single-institution cohort study reported in JAMA Network Open, Jason A. Mouabbi, MD, and colleagues found no difference in survival outcomes between patients with hormone receptor–positive metastatic breast cancer with low vs no HER2 expression who received targeted therapy and endocrine therapy.
Jason A. Mouabbi, MD
Study Details
The study involved 1,585 women with low or no HER2 expression on immunohistochemical analysis treated at The University of Texas MD Anderson Cancer Center between January 2010 and December 2021 with targeted therapy (cyclin-dependent kinase [CDK]4/6 inhibitors, everolimus, or alpelisib) plus endocrine therapy (aromatase inhibitors, fulvestrant). The main outcome measures were median progression-free survival and overall survival.
Key Findings
Among the 1,585 women included in the study, 1,013 (63.9%) had low HER2 expression and 572 (36.1%) had no HER2 expression. A total of 1,084 patients (68.4%) received CDK4/6 inhibitor treatment; among these, 84.2% of those in the low-expression group and 83.9% in the no-expression group received first-line treatment and 15.8% vs 16.1% received second-line treatment. A total of 475 patients (30.0%) received everolimus, including 29.6% in the low-expression group vs 30.5% in the no-expression group; a total of 26 patients (1.6%) received alpelisib, including 1.6% vs 1.9%. Among patients receiving first-line CDK4/6 inhibitor treatment, 618 (67.8%) received an aromatase inhibitor as endocrine therapy and 265 (29.1%) received fulvestrant.
Among all patients treated with targeted therapies and endocrine therapy, median follow-up was 17.9 months (range = 1–111 months). No significant differences between the low-expression vs no-expression groups were observed for median progression-free survival (9.1 vs 9.1 months, P = .43) or median overall survival (28.1 vs 26.4 months, hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.92–1.21, P = .41).
Among patients treated with first-line CDK4/6 inhibitors and endocrine therapy, median follow-up was 17.5 months (range = 1–110 months). No significant differences between the low-expression vs no-expression groups were observed in median progression-free survival (13.0 vs 11.6 months, HR = 1.09, 95% CI = 0.92–1.29, P = .27) or median overall survival (32.4 vs 31.2 months, HR = 1.14, 95% CI = 0.92–1.39, P = .22).
Among patients treated with second-line CDK4/6 inhibitors, everolimus, or alpelisib and endocrine therapy, median follow-up was 12.4 months (range = 1–78 months). No significant differences between the low-expression vs no-expression groups were found for median progression-free survival (7.3 vs 7.1 months, HR = 1.20, 95% CI = 0.83–1.72, P = .31) or median overall survival (31.5 vs 24.9 months, HR = 1.24, 95% CI = 0.80–1.92, P = .32) among patients receiving CDK4/6 inhibitors with endocrine therapy. No significant differences in median progression-free survival (6.5 vs 6.0 months, HR = 1.08, 95% CI = 0.87–1.33, P = .46) or median overall survival (21.3 vs 19.0 months, HR = 1.01, 95% CI = 0.82–1.25, P = .88) were found among patients receiving everolimus or alpelisib with endocrine therapy.
The investigators concluded, “In this cohort study of patients with hormone receptor–positive metastatic breast cancer treated with targeted therapy plus endocrine therapy, low HER2 expression did not have a significant association with prognosis.”
Dr. Mouabbi, of the Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
