Trop-2 as a Therapeutic Target in Breast Cancer

SIMPLE SUMMARY: Trop-2 is an exciting, new target for the treatment of breast cancer. Trop-2 is found at high levels in multiple cancers such as prostate, pancreatic, urothelial, lung, and breast cancer. Among different breast cancer subtypes, Trop-2 is most highly expressed in triple negative breast cancer. Drugs that inhibit Trop-2 are now an important treatment option for patients with metastatic triple negative breast cancer, for whom few treatment options exist. The benefit of Trop-2 inhibitors has also been observed in patients with hormone receptor positive breast cancer, whose tumors are resistant to standard treatments. Ongoing studies are working to understand if patients can benefit from different drug combinations with Trop-2 inhibitors in the metastatic setting and if Trop-2 inhibition can benefit patients with early stage disease. ABSTRACT: The emergence of Trop-2 as a therapeutic target has given rise to new treatment paradigms for the treatment of patients with advanced and metastatic breast cancer. Trop-2 is most highly expressed in triple negative breast cancer (TNBC), but the receptor is found across all breast cancer subtypes. With sacituzumab govitecan, the first FDA-approved, Trop-2 inhibitor, providing a survival benefit in patients with both metastatic TNBC and hormone receptor positive breast cancer, additional Trop-2 directed therapies are under investigation. Ongoing studies of combination regimens with immunotherapy, PARP inhibitors, and other targeted agents aim to further harness the effect of Trop-2 inhibition. Current investigations are also underway in the neoadjuvant and adjuvant setting to evaluate the therapeutic benefit of Trop-2 inhibition in patients with early stage disease. This review highlights the significant impact the discovery Trop-2 has had on our patients with heavily pretreated breast cancer, for whom few treatment options exist, and the future direction of novel Trop-2 targeted therapies.