Prognostic Role of Inflammatory Indices and Real-World Outcomes in HER2-Positive Metastatic Breast Cancer Treated with Trastuzumab Emtansine

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Abstract
Background and Objectives: Reliable pretreatment biomarkers to guide treatment selection in HER2-positive metastatic breast cancer (mBC) remain an unmet need. Systemic inflammatory indices derived from routine blood tests have emerged as accessible prognostic markers. This study evaluated the prognostic value of inflammation-based indices in patients with HER2-positive mBC treated with trastuzumab emtansine (T-DM1). Materials and Methods: In this retrospective single-center cohort study, 50 patients with HER2-positive mBC treated with T-DM1 in the second-line setting were analyzed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. ROC analysis assessed the prognostic performance of the CRP/albumin ratio (CAO), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Variables associated with PFS were further evaluated using multivariable Cox regression. Results: The median follow-up was 46 months. Median OS from initial diagnosis and median PFS from T-DM1 initiation were 96 and 7 months, respectively. Metastatic pattern (p = 0.010), CNS involvement at T-DM1 initiation (p = 0.025), liver metastasis (p = 0.041), and best radiologic response (p < 0.001) were associated with PFS. ROC analysis showed modest discrimination (CAO AUC 0.694, NLR 0.658, PLR 0.646, and SII 0.653). In multivariable analysis, best radiologic response to T-DM1 was strongly associated with progression risk and appeared to reflect treatment sensitivity rather than acting as a pretreatment predictor. Conclusions: T-DM1 provided meaningful disease control in this real-world cohort. Treatment response was the main determinant of progression, while baseline inflammatory markers offered modest complementary prognostic value. These findings may aid patient selection for T-DM1, particularly in settings with limited access to trastuzumab deruxtecan.

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