Abstract OT1-02-02: A pilot study to examine the feasibility of measuring CTC and inflammatory biomarker changes resulting from atorvastatin as adjuvant therapy in TNBC and TN-IBC patients with residual disease after neoadjuvant chemotherapy
Authors: Alexander Angela , Fujii Takeo , Stauder Michael C , Woodward Wendy A , Reuben James M , Shen Yu , Liu Diane , Reddy Sangeetha M , Valero Vicente , Gilchrist Susan C , Lim Bora , Lucci Anthony , Ueno Naoto T , Barcenas Carlos H 
Published: March 2020

Abstract
Background: Patients who have TNBC or triple negative-IBC (TN-IBC) and do not achieve pathological complete response after neoadjuvant chemotherapy are at significant risk for distant relapse and death from recurrent disease. Apart from capecitabine, there are no proven adjuvant therapies that may improve these poor outcomes of patients with chemo-resistant tumors. Therefore, there is an unmet need for effective systemic therapy for this subset of patients with TNBC. Epidemiological evidence reveals that statin use after diagnosis is associated with improved breast cancer relapse-free survival and decreased mortality. However, direct evidence of in vivo mechanisms explaining this association are lacking. Preclinical studies using statins in breast cancer reveal pathways that statins can inhibit proliferation, stem cell self-renewal and metastatic potential.
Trial Design: This is a pilot study designed in 2 phases to assess feasibility of completion while providing a signal of efficacy in biomarker changes. In the first phase, we will follow the initial 30 patients who meet eligibility for atorvastatin treatment for the 2-year treatment window, or until disease recurrence. We will collect blood samples prior to, and during atorvastatin treatment for circulating tumor cells (CTCs), cytokine and inflammatory biomarker analyses. We defined a positive outcome as CTCs remaining non-detected at 6 months when baseline CTC is undetected, or a reduction in the number of CTCs at 6 months compared to baseline. If we observe a positive outcome among the initial 30 patients, then we will open the second phase of this study for an additional 50 patients. Here we will follow both patient cohorts who receive and not receive atorvastatin treatment to collect longitudinal data on biomarkers as a function of the natural history of TNBC to better understand the activity of atorvastatin.
Trial Eligibility: Patients with stage II-III TNBC who have residual cancer burden (RCB)-II or RCB-III or stage 3 TN-IBC with any amount of residual disease, and are not taking a statin or any other anti-lipidemic agent are candidates for the study. Patients must have adequate hematologic, organ, and cardiac function and must have recovered from the acute effects of any prior treatments. Baseline lipid profile will be assessed by a cardiologist to determine the patients’ eligibility to take atorvastatin based on current ACC/AHA guideline, and to select between moderate (20mg) or high intensity treatment (40mg).
Specific Aims: The primary objective is to determine the proportion of patients with undetectable CTCs at 6 months with and without atorvastatin therapy. Secondary objectives include correlation of baseline lipid profiles/lipid profile changes with 2 year-relapse free survival (RFS), CTC counts and inflammatory biomarkers.
Statistical Methods: The total estimated enrollment is 80 patients, including at least 5 treated with adjuvant capecitabine and at least 5 without adjuvant capecitabine. The study overall is powered with the assumption that 48 patients will receive atorvastatin and 32 will not, and this will allow us to estimate the percent of patients with negative CTCs at 6 months with a standard error not larger than 7% and 9%, respectively. All other analyses including inflammatory biomarkers and RFS differences between groups are exploratory and considered hypothesis-generating rather than conclusive.
Citation Format: Angela Alexander, Takeo Fujii, Michael C Stauder, Wendy A Woodward, James M Reuben, Yu Shen, Diane Liu, Sangeetha M Reddy, Vicente Valero, Susan C Gilchrist, Bora Lim, Anthony Lucci, Naoto T Ueno, Carlos H Barcenas. A pilot study to examine the feasibility of measuring CTC and inflammatory biomarker changes resulting from atorvastatin as adjuvant therapy in TNBC and TN-IBC patients with residual disease after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-02-02.