Associations with Pathological Complete Response in Hormone Receptor-Negative and Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Real-World Study

INTRODUCTION: Hormone receptor-negative, human epidermal growth factor receptor 2-positive (HR−/HER2+) breast cancer is an aggressive subtype with high sensitivity to human epidermal growth factor receptor 2 (HER2)-targeted neoadjuvant therapy. Although pathologic complete response (pCR) is associated with improved outcomes, real-world predictors of pCR remain unclear. This study aimed to evaluate clinical and pathological factors associated with pCR in patients with HR−/HER2+ breast cancer.
METHODS: This retrospective real-world study included 73 patients with HR−/HER2+ breast cancer treated with neoadjuvant systemic therapy. Clinicopathological features, laboratory parameters, and treatment regimens were collected. HER2 and hormone receptor status were assessed by immunohistochemistry and fluorescence in situ hybridization when indicated. pCR was defined as the absence of invasive disease in the breast and axillary lymph nodes. We examined potential clinical and pathological factors associated with pCR in HR−/HER2+ breast cancer.
RESULTS: The median age was 50.9 years, and all patients were female. Dual HER2 blockade was administered in 63% of patients. Overall, pCR was achieved in 67.1% of cases. Comparison of baseline clinicopathological characteristics according to pCR showed that pre/peri menopausal patients achieved significantly higher pCR rates than postmenopausal patients (80.6% vs. 57.1%, p=0.030). In multivariate analysis, the presence of comorbidity (odds ratio [OR]: 7.44, p=0.012), age (OR: 0.88, p=0.003), menopausal status (OR: 5.31, p=0.011), and the number of neoadjuvant cycles (OR: 0.45, p=0.028) were identified as statistically significant predictors.
DISCUSSION AND CONCLUSION: Neoadjuvant therapy achieved high pCR rates in this real-world HR−/HER2+ breast cancer cohort. Menopausal status remained a significant clinical factor associated with pCR. Moreover, age, the number of neoadjuvant cycles, and comorbidity were also identified as significant factors. These real-world findings require validation in larger cohorts, and further prospective studies incorporating molecular biomarkers are warranted.

Keywords: Breast cancer, hormone receptor-negative, human epidermal growth factor receptor 2-positive, pathological complete response, predictors.