Composite CA15-3, LDH, and Albumin Index as a Predictor of Survival in HER2-Positive Metastatic Breast Cancer Treated with Trastuzumab Emtansine.

Background/Objectives: Trastuzumab emtansine (T-DM1) is widely used in Human Epidermal Growth Factor Receptor2 (HER2)-positive metastatic breast cancer; however, outcomes vary, and reliable prognostic markers remain limited. We developed the CALA index as a composite biomarker integrating CA15-3, lactate dehydrogenase (LDH), and albumin. This study aimed to evaluate the prognostic value of the CALA index in metastatic breast cancer treated with T-DM1. Methods: This multicenter retrospective study included 168 patients treated with T-DM1 across four tertiary centers. The CALA index was calculated using pretreatment levels of CA15-3, LDH, and albumin. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value, and patients were stratified into groups accordingly. Survival outcomes and independent risk factors were assessed using Kaplan-Meier and Cox regression analyses. Results: The median overall survival (OS) was 26 months (95% CI: 21.3-30.7). ROC analysis identified an optimal CALA cutoff value of 118.3. Patients with CALA ≤ 118.3 demonstrated significantly longer OS compared with those with CALA > 118.3 (log-rank p = 0.006), with 1- and 3-year OS rates of 81.2% and 43.2% versus 69.8% and 22.7%, respectively. In univariate analysis, CALA > 118.3 was associated with worse OS (HR: 1.699; 95% CI: 1.151-2.506; p = 0.008), and this association remained significant in multivariate analysis (HR: 1.671; 95% CI: 1.088-2.565; p = 0.019). Conclusions: The CALA index was associated with overall survival in metastatic breast cancer treated with trastuzumab emtansine and may serve as a practical tool for risk stratification.