First-Line Dual Versus Single HER2-Targeted Therapy With Docetaxel for Advanced HER2-Positive Breast Cancer

This retrospective observational cohort study emulates a target trial to compare the effectiveness and safety of two first-line treatment strategies for women with HER2-positive unresectable locally advanced, recurrent, or metastatic breast cancer in routine clinical practice: pertuzumab plus trastuzumab and docetaxel versus trastuzumab and docetaxel. Data were obtained from electronic health records held by the National Health and Medical Big Data (Eastern) Center and linked with the Jiangsu Provincial Mortality Registry. Eligible patients initiated one of the two treatment strategies between January 1, 2020, and December 31, 2024. Time zero was defined as the date of the first administration of the qualifying first-line regimen. No minimum number of treatment cycles was required. The primary outcome was overall survival. Secondary outcomes included progression-free survival and prespecified adverse events.

Inclusion Criteria: 1. Female patients aged 18 years or older on the index date. 2. Histologically or cytologically confirmed breast cancer. 3. HER2-positive disease, defined according to available pathology records as immunohistochemistry (IHC) 3+ or IHC 2+ with positive in situ hybridization. 4. Unresectable locally advanced, recurrent, or metastatic breast cancer on the index date. 5. No prior systemic anticancer therapy for unresectable locally advanced, recurrent, or metastatic breast cancer before the index date. 6. Initiation of first-line treatment with either: 1. pertuzumab plus trastuzumab plus docetaxel; or 2. trastuzumab plus docetaxel between January 1, 2020 and December 31, 2024. 7. Sufficient information available on or before the index date to determine eligibility, treatment assignment, and baseline covariates. Exclusion Criteria: 1. Early-stage or resectable breast cancer treated with curative intent on the index date. 2. Prior systemic anticancer therapy for unresectable locally advanced, recurrent, or metastatic breast cancer before the index date. 3. Another active primary malignant tumor on the index date that was expected to materially affect survival. 4. Insufficient or invalid information to determine HER2 status, advanced disease status, index treatment regimen, or index date. 5. Absence of a valid patient identifier required for linkage between the electronic health record database and the mortality registry.