Abstract 778: Atorvastatin modulates serum biomarkers in women at increased risk for breast cancer

Abstract

Abstract Background Tamoxifen and Aromatase inhibitors have been shown to be highly effective at reducing the incidence of ER-positive breast cancers in women at increased risk, but there are no approved agents for the risk reduction of ER-negative cancers. Evidence from observational and preclinical studies supports the study of statins for breast cancer risk reduction. Objective This study aimed to investigate the effects of Atorvastatin treatment on serum and tissue biomarkers in women at increased risk for breast cancer. Methods Women at increased risk for breast cancer were accrued prospectively at UTMDACC, Breast Medical Oncology High-Risk Clinic. The study was approved by the IRB and all participants signed informed consent. High risk was defined as having a previous history of DCIS, LCIS, or atypical hyperplasia, 5-year projected Gail risk >1.67 %, or lifetime risk >20 % calculated by clinical models. Patients were randomized to no treatment (n=15) or daily 10mg (n=15), 20mg (n=14), or 40mg (n=16) Atorvastatin for 3 months. Fasting blood and breast tissue samples via fine needle aspiration (FNA) were collected at baseline and at study completion. Serum biomarkers were analyzed with ELISA (R&D Systems). The IGF1/IGFBP3 molar ratio was calculated using [IGF1 (ng/mL) x 0.13]/[IGFBP-3 (ng/mL) x 0.035]. The Wilcoxon matched-pairs signed rank test was used to determine significance. Results Tissue biomarker evaluation was previously reported. Serum biomarker levels of IGF1 and its main binding proteins IGFBP1 and IGFBP3 were compared in baseline and post-intervention samples by ELISA analysis. The average change in serum IGF1 (ng/mL) levels between pre- and post-treatment samples (represented as average difference with interquartile range) was +3.5 (-16.8 to 8.7) p=0.98, -0.6 (-23.6 to 15.4) p=0.64, -1.76 (-27.7 to 28.6) p=0.81, and +2.6 (-14.5 to 32.2) p=0.67 in the 0, 10, 20, and 40mg groups respectively. The average change in serum IGFBP1 (pg/mL) was -23.2 (-2372 to 4487) p=0.33, -480 (-4567 to 3008) p=0.72, 429 (-1259 to 3039) p=0.54, and -250 (-3581 to 2492) p=0.94 in the 0, 10, 20, and 40mg groups. The average change in serum IGFBP3 (ng/mL) was -24 (-193 to 98) p=0.72, -119 (-353 to 111) p=0.17, -190 (-433 to 14) p=0.07, and -234 (-369 to -79) p=0.002 in the 0, 10, 20, and 40mg groups. Serum IGF1/IGFBP3 molar ratio was +0.012 (-0.018 to 0.026) p=,0.76, +0.0065 (-0.013, to 0.047) p=0.53, +.0073 (-0.036 to 0.045) p=0.86, and +.027 (-.011 to .062) p=0.058 in the 0, 10, 20, and 40mg groups. Conclusions Serum IGFBP3, which has been associated with breast cancer risk, was decreased in a dose-dependent manner in patients treated with Atorvastatin. The IGF1/IGFBP3 molar ratio was increased in the 40mg group, although not statistically significant (p=.0577). This shows that treatment with Atorvastatin induced changes in circulating biomarkers and that Atorvastatin could be further studied in larger prospective breast cancer prevention trials. Citation Format: Amanda L. Lanier, Johannes Fahrmann, Fatma N. Mustafayev, Angelica Gutierrez Barrera, Powel H. Brown, Banu Arun. Atorvastatin modulates serum biomarkers in women at increased risk for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 778.