SREBP1-Dependent Metabolism as a Potential Target for Breast Cancer Risk Reduction

Abstract

Breast cancer prevention remains a major challenge, despite the availability of endocrine therapies such as tamoxifen and aromatase inhibitors. Adverse effects, including arthralgia, are associated with poor uptake of endocrine therapy in the prevention setting, with more than 85% of risk-eligible women opting to discontinue their use or decline taking them a priori. Non-endocrine therapies with sufficient efficacy and minimal toxicities are needed. The master regulator of lipogenesis, sterol regulatory element binding protein 1 (SREBP1), has emerged as an important driver of breast cancer development, and, as such, a potential target for breast cancer interception. Following the review of studies published between 2015 and 2025, this manuscript summarizes the evidence for SREBP1 being a promising target to block breast cancer at multiple steps ranging from early to metastatic lesions. Our review identifies SREBP1 as a prognostic marker and supports disrupting SREBP1 activation, stabilization, and translocation to the nucleus as feasible targets for breast cancer prevention or interception. We conclude that SREBP1 is a promising non-endocrine target that can be exploited for breast cancer risk reduction in high-risk women. It needs to be further studied to define any potential side effects.