Study findings show that clinical stage determines overall survival (OS) and pathologic complete response (pCR) outcomes in patients with HER2-positive (HER2+) breast cancer receiving neoadjuvant chemotherapy (NAC). The data were published in the Annals of Surgical Oncology by researchers from Mayo Clinic.
Microscopic visualization of breast cancer cells | Image Credit: © Jack – stock.adobe.com
HER2-expressing breast cancers—including HER2-positive, HER2-negative, HER2-low, and HER2-ultralow—are relatively common, accounting for approximately 20% of all diagnoses. They are associated with increased risk of disease recurrence and poorer treatment responses, underscoring the importance of continued innovation in therapeutic approaches throughout the treatment plan. NAC is associated with improved survival and pCR rates in patients with HER2-positive breast cancer, but the relationship between NAC response and disease stage has not been fully understood in clinical practice.
Using the National Cancer Database, the researchers collected data from patients with HER2-positive breast cancer (n = 57,671) who received NAC between 2013 and 2020. Using multivariable Cox proportional hazards regression, overall survival was evaluated by clinical stage at presentation and treatment response, stratified by hormone receptor (HR) status.
At 5 years, 98% of patients with pCR with stage 1 disease achieved an OS of 98%. Those with stages 2 and 3 diseases were not far behind at 97% and 91%, respectively (P < .001).
Among patients with residual disease, the 5-year OS rates were 95% for those with stage 1 disease, 91% for stage 2 disease, and 80% for stage 3 disease (P < .001). In a multivariable analysis, stage 3 HR-negative/HER2-positive disease with a pCR was found to have OS outcomes that were not significantly different from those of stage 1 breast cancer with residual disease (hazard ratio [HR], 1.17; P = 0.34). Similarly, stage 2 HR-positive/HER2-positive disease with pCR did not differ in OS compared with stage 1 breast cancer with residual disease (HR, 0.94; P = 0.61). However, stage 3 disease with pCR was associated with significantly worse OS compared with stage 1 breast cancer with residual disease (HR, 1.90; P < .001).
These findings highlight the critical role of clinical stage in guiding prognosis and therapeutic expectations for HER2-positive breast cancer patients. They also underscore the need for stage-specific strategies to optimize NAC outcomes and improve long-term survival, particularly for patients with advanced-stage disease who achieve pCR but remain at elevated risk.