Abstract
Human epidermal growth factor receptor 2 (HER2)-targeting therapies have become crucial in the management of HER2-positive breast cancer. Trastuzumab emtansine (T-DM1) is a microtubule inhibitor and HER2-targeted antibody conjugate. T-DM1 resistance is most likely influenced by factors involved in the biological mechanisms of T-DM1 action. This study aimed to examine the efficacy of statins, which influence HER-2-based therapies via the caveolin-1 (CAV-1) protein, in female breast cancer patients receiving T-DM1. Our study included 105 patients with HER2-positive metastatic breast cancer treated with T-DM1. The progression-free survival (PFS) and overall survival (OS) of patients who received statins concurrently with T-DM1 versus those who did not were compared. During the median 39.5 (95% confidence interval [CI]: 35.6-43.5) months of follow-up, 16 (15.2%) patients received statins, and 89 (84.8%) patients did not. Median OS was significantly higher in patients using statins than in patients not using statins (58.8 vs 26.5 months, P = .016). The association between statin use and PFS did not reach statistical significance (34.7 vs 9.9 months, P = .159). Multivariate Cox regression analysis showed that better performance status (hormone receptor [HR]: 0.30, 95% CI: 0.13-0.71, P = .006), use of trastuzumab plus pertuzumab prior to T-DM1 (HR: 0.37, 95% CI: 0.18-0.76, P = .007) and use of statins with T-DM1 (HR: 0.29, 95% CI: 0.12-0.70, P = .006) were independent factors that prolong OS duration. Our study showed that T-DM1 is more effective at treating HER2-positive breast cancer in people who receive statins concurrently with T-DM1 than those who do not.