Background Different estrogen receptor (ER) and progesterone receptor (PR) expression patterns have important biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, little is known about hormone receptor (HR)-positive and triple-positive subtypes, making therapy selection and survival prognosis difficult. This study investigated the clinical characteristics and nomogram-predicted survival of patients with HER2-positive breast cancer. Materials and methods Data on patients with HER2-positive breast cancer were retrieved from the Surveillance, Epidemiology, and End Results database. Comparisons were carried out between single HR-positive and double HR-positive/double HR-negative subtypes. A nomogram-based model of predicted outcomes was developed. Results This cohort study included 34 819 patients with breast cancer (34 606 women and 213 men). Single HR-positive and double HR-positive/double HR-negative subtypes showed distinct clinicopathological characteristics. Multivariable Cox regression analysis showed that patients with ER-positive/PR-negative/HER2-positive [hazard ratio (HR) = 1.24; 95% confidence interval (CI): 1.14-1.39], ER-negative/PR-positive/HER2-positive (HR = 1.56; 95% CI: 1.23-1.97), and ER-negative/PR-negative/HER2-positive (HR = 1.56; 95% CI: 1.43-1.70) subtypes had worse breast cancer-specific survival than patients with the triple-positive subtype. Thirteen clinical parameters were included as prognostic factors in the nomogram: age, sex, race, grade, histology type, bone, brain, liver, and lung metastasis, TNM (tumor–node–metastasis) staging, and molecular subtype. The C-index was 0.853 (95% CI: 0.845-0.861). Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 3-year and 5-year prognoses. Conclusions Significant differences in survival rates were observed between single HR-positive and double HR-positive/double HR-negative subtypes. A nomogram accurately predicted survival. Different treatment strategies may be required for HER2-positive patients with single HR-positive and double HR-positive tumors to ensure optimal treatment and benefits.
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