New treatment options for hormone receptor positive breast cancer in 2023

Hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer does respond to chemotherapy but can be addressed with a better therapeutic index by using biologically modified endocrine therapy. The most pronounced recent successes were reached by antibody drug conjugates (ADCs).

In early HR+/HER2- disease, adjuvant treatment escalations have taken place for high-risk patients using abemaciclib for the HR+ BRCA- subset and olaparib for HR+ BRCA+ patients. In metastatic spread, among all CDK (cyclin-dependent kinase) 4/6 inhibitors used for first-line therapy, only ribociclib improved overall survival in pre and postmenopausal patients. Palbociclib failed to demonstrate overall survival benefits. New options come up with oral selective oestrogen receptor degraders (SERDs) such as elacestrant, which will replace fulvestrant and is clinically important in combination therapies. ADCs, together with new patient categories such as HER2low or HER3+, enlarge the treatment portfolio and challenge the need of supportive care. The antitrophoblast antigen 2 (TROP2) ADC sacituzumab govitecan improves overall survival in heavily pretreated HR+/HER2- patients by 3.2 months. The best improvement of overall survival was shown bý trastuzumab deruxtecan in less pretreated HER2low (HER2 1+ or HER2 2+/no gene amplification) patients with a gained life span of 6 months.

Real-world data on the sequence of different ADCs with similar payloads are needed to establish best possible treatment algorithms. All these new agents will find their place after CDK4/6 inhibitor-based endocrine combination therapy.