Endocrine therapy is the backbone of treatment for patients with hormone receptor (HR)-positive, HER2-negative, metastatic breast cancer. The introduction of novel endocrine medication combinations as a result of tumor resistance to hormone therapy has changed the landscape of metastatic breast cancer care. The possibilities of endocrine therapy are growing, with promising agents on the horizon. Despite the fact that metastatic breast cancer is incurable, many people can live for years with a good quality of life by cycling through the various treatments available. Because of the large number of available agents and the speed with which they are approved, physicians rely on evidence-based guidelines to help them choose the best treatment for their patients.1
Combining endocrine therapy with cyclin-dependent kinase (CDK)4/6 inhibitors is one of the most successful combinations, both as initial therapy and after progression on endocrine therapy. These combinations enhanced progression-free survival and objective response rates in patients with HR-positive advanced breast cancer.2 Patients with HR-positive, HER2-negative, metastatic breast cancer had a median survival of 16 to 26 months prior to the development of CDK4/6 inhibitors. CDK4/6 inhibitors have significantly altered the landscape of metastatic breast cancer, resulting in unprecedented improvements in progression-free survival and overall survival.1
In addition to CDK4/6 inhibitors, research has enhanced our understanding of advanced breast cancer biology, resulting in the identification of additional targets to complement endocrine therapy. These include mTOR inhibitors, histone deacetylase inhibitors, and phosphoinositide 3-kinase inhibitors. The fast development and approval of new therapies might make it difficult to determine which treatment option is optimal for a patient. Physicians will need to rely on evidence-based guidelines in their clinical practice.1
Given the intricacy of these medications, identifying patient and tumor features that can assist with when and in which patients to use CDK4/6 inhibitors in the therapy paradigm is a hot topic. To date, a number of CDK4/6 inhibitor trials have shown that adding a CDK4/6 inhibitor to endocrine therapy improves treatment outcomes across all patient subgroups.3 Alternative treatment techniques should be given special consideration for elderly patients and those with baseline neutropenia or poor performance status. The capacity to undertake next-generation sequencing has transformed the metastatic breast cancer paradigm.1 Patients with HR-positive, HER2-negative, metastatic breast cancer should have new hope as research into combining endocrine therapies with newer targeted medicines and immunotherapy continues.1
- Manohar PM, Davidson NE. Updates in endocrine therapy for metastatic breast cancer. Cancer Biol Med. 2021 Oct 5. Epub ahead of print.
- Di Leo A, O’Shaughnessy J, Sledge Jr GW, et al. Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy. NPJ Breast Cancer. 2018;4:41.
- Andrahennadi S, Sami A, Manna M, et al. Current landscape of targeted therapy in hormone receptor-positive and HER2-negative breast cancer. Curr Oncol. 2021;28:1803-1822.