Background: Micrometastases from breast cancer (BC) might undergo quiescence following adjuvant therapies. Oftentimes they reactivate, prompting metastatic relapse and aggressive, uncurable disease. It is necessary to find alternative, safe therapies that could be used as adjuvants for delaying the dormancy process and reduce metastatic breast cancer (MBC) progression. Prior epidemiological studies found prolonged overall survival from chronic statin use. However, the effectiveness of statin use through different stages of progression, including advanced MBC, has not yet been defined. Methods: A real-world, retrospective analysis of 1,016 deceased patients with MBC treated from 1999-2019 at the University of Pittsburgh Medical Center (UPMC). Lipophilic statin (atorvastatin and simvastatin) use and dosing were retrieved from medical records through an IRB-approved R3 request and merged with already available clinical variables. A total of 122 patients were included in the analysis as the statin use group. This included patients who were prescribed statins through the course of their breast cancer. For measuring time to relapse, only patients with statin prescription before being diagnosed with MBC were selected. Log-ranks were used to compute survival. Uni- and multi-variate Cox hazard models were also applied. Statistical analysis was computed using the package ggpubr on R v3.6.3.Results: Women who used statins were older at the time of detection of primary (60 vs 52 years of age, respectively) and MBC (66 vs 56 years of age, respectively). An almost 2-fold reduction was found in the onset of liver metastasis as first relapse in the statin group, compared to general population (5.7% vs 10.4%, respectively). Increased overall survival (OS) was found among statin users who had ER (+) (p<0.05), and HER2 (-) (p<0.05) BC. Statins were associated with an increase in time from diagnosis until relapse, in ER (+) (p=0.03) and HER2(-) (p=0.02) patients with BC. Patients with ER (-), HER2 (-) MBC also seemed to partially benefit from statin use (p=0.09). Multivariate analysis adjusted for age, ER-status, statin use, and adjuvant chemotherapy also predicted increased OS for patients using statins. No differences in survival were seen when measuring time from metastatic diagnosis to death, suggesting that statins may be effective in prolonging dormancy but lack benefit against relapsing MBC.Conclusion: Lipophilic statins may prolong dormancy and overall survival but not slow the progression of relapsing metastatic breast cancer.

Citation Format: Juan Luis Gomez Marti, Alan Wells. Lipophilic statins for prolonging dormancy and overall survival: A real-world retrospective investigation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-22.