Real-world outcomes of first-line THP in de-novo HER2-positive metastatic breast cancer: a retrospective analysis of prognostic factors Including hormone receptor status, performance status, and metastatic pattern

Aims: Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab, pertuzumab, and docetaxel (THP) is standard first‑line therapy for de‑novo HER2‑positive metastatic breast cancer (MBC). Real‑world data on prognostic factors such as hormone receptor (HR) status, performance status, and metastatic sites remain limited. This retrospective study evaluated clinical outcomes in a consecutive cohort of de‑novo HER2‑positive MBC patients treated with first‑line THP. Methods: Fifty‑three de‑novo HER2‑positive MBC patients receiving first‑line THP were analyzed. Baseline characteristics, progression‑free survival (PFS), and overall survival (OS) were assessed according to HR status, Eastern Cooperative Oncology Group (ECOG) performance status, and metastatic sites. Kaplan‑Meier and univariable Cox proportional hazards models were used. Median follow‑up was 34.2 months (interquartile range: 22.5-46.1). Due to limited sample size, a parsimonious multivariable model including age, ECOG, and liver metastasis was performed for OS only, with results interpreted cautiously. Multivariable analysis for PFS was not performed to avoid overfitting. Results: HR‑positive patients (60.4%) were older than HR‑negative patients (median 61.0 vs. 46.0 years, p<0.001). Median PFS and OS for the overall cohort were 22.8 months (95% confidence interval: 19.2-26.4) and 49.1 months (95% confidence interval: 44.3-53.9), respectively. HR status did not significantly stratify PFS (p=0.111) or OS (p=0.389). ECOG 0 versus 1‑2 showed marked survival differences: median PFS 31.5 vs. 18.9 months, median OS 64.6 vs. 51.2 months (both p<0.001). Liver and lung metastases were associated with worse OS in univariable analysis (hazard ratio: 2.47, p=0.016; hazard ratio: 2.53, p=0.013, respectively). In a parsimonious multivariable model for OS, ECOG 1‑2 (hazard ratio: 7.82, 95% confidence interval: 2.41-25.36, p=0.001) and liver metastasis (hazard ratio: 2.18, 95% confidence interval: 1.02-4.66, p=0.044) remained significant, while HR status did not (p=0.412). Age was associated with PFS (hazard ratio: 1.61 per 10‑year increase, p=0.001) but not OS. Conclusion: In this real‑world THP‑treated de‑novo cohort, HR status alone did not significantly discriminate survival outcomes despite baseline age differences. ECOG performance status and visceral metastases were dominant prognostic factors in univariable analysis and remained significant in a parsimonious multivariable model for OS. However, these findings should be interpreted cautiously and validated in larger prospective cohorts with multivariable analyses.