Detection of Candidate Circular RNAs to Monitor Anti-Hormonal Response in the Mammary Gland

Abstract Anti-hormonal therapies such as selective estrogen receptor modulators like tamoxifen or aromatase inhibitors like letrozole represent a cornerstone for breast cancer prevention and therapy of estrogen receptor-positive breast cancer. Therapeutic monitoring can include blood tests and imaging; however, genetically-based approaches are not yet in practice. Ideally, a test would be able to detect a positive molecular response across different estrogen pathway-suppressive approaches. Circular RNAs are a species of non-coding RNAs detectable in plasma that have been proposed as non-invasive therapeutic biomarkers. To determine whether a set of specific circular RNAs is altered across estrogen-suppressive pathway approaches, we analyzed mammary gland-specific total RNA sequencing data from two individual genetically engineered mouse models (GEMMs) of estrogen pathway-induced breast cancer, with or without exposure to tamoxifen or letrozole. The nf-core/circrna pipeline was used to identify circRNAs that were differentially expressed in response to either tamoxifen or letrozole. We then screened for circRNAs that were differentially regulated by both anti-hormonals. Four up-regulated and 31 down-regulated circRNAs with host genes known to be expressed in human breast epithelial cells were identified as showing reproducible differential regulation in response to anti-hormonal treatment.