Revolutionary Strategies for HR+ Metastatic Breast Cancer Treatment Medscape

Latest Therapies and Treatment Strategies for Metastatic Breast Cancer

Introduction

Metastatic hormone receptor-positive (HR+) or estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer is a complex condition that requires advanced medical care and treatment strategies. In this article, we will discuss the latest therapies and strategies for treating metastatic HR+/ER+ HER2- breast cancer.

Standard First-Line Therapy

The current standard of care for patients with metastatic breast cancer, in most first-world countries, is to provide endocrine therapy combined with cyclin-dependent kinase (CDK)-4/6 inhibitors. This combination is recommended for all patients except those who have a visceral crisis. Endocrine therapy involves the use of hormone-blocking drugs to stop the growth of cancer cells. CDK4/6 inhibitors prevent cancer cells from dividing and, therefore, slow the progression of the disease.

The standard of care for most patients with HR+/ER+ HER2- breast cancer is to receive ribociclib, a CDK4/6 inhibitor drug, as it has shown an overall survival benefit. However, if ribociclib is contraindicated, palbociclib is a good alternative. Additionally, ovarian function suppression is required for premenopausal women.

Second-Line Therapy

In the event of patient progression on CDK4/6 inhibitors, clinicians should conduct further workup tests to identify the mutation status of the patient. ESR1 mutation, PI3KCA mutation, or AKT1 alterations are commonly seen in such cases. Tumor DNA sequencing is performed before the first-line therapy to have an idea of the patient’s genomic mutation, making it easier to select appropriate drugs during CDK4/6 inhibitors failure.

For PI3KCA mutations, the use of Alpelisib, a potent drug, can help treat metastatic breast cancer. However, patients who don’t have a mutation in the second line setting can receive either an everolimus combination or an elacestrant. The everolimus combination is a viable option due to its low side effect profile for wild-type patients. On the other hand, elacestrant, which is an oral drug with partial estrogen receptor agonist and antagonist properties, can be used solely against HR+/ER+ HER2- metastatic breast cancer with an ESR1 mutation.

CDK4/6 inhibitors can still be used for patients who have progressed with another regimen. The recent discovery is that subsequent lines of CDK4/6 inhibitors therapy could also improve overall survival for these patients. Additionally, chemotherapy should remain a single agent, unless rapid response is needed.

Third-Line Therapy and Beyond

It is uncommon for patients to respond to more than two lines of endocrine therapy. Therefore, after clinical progression on endocrine therapy and CDK4/6 inhibitors, chemotherapy is the recommended strategy. Typically, clinicians suggest chemotherapy when the patient is immunoresistant and is unlikely to respond to further therapy.

Overall, we have many new drugs available to treat metastatic HR+/ER+ HER2- breast cancer. Trastuzumab deruxtecan and sacituzumab are two of the latest drugs proving efficient in treating metastatic HER2- breast cancer.

Conclusion

Metastatic HR+/ER+ HER2- breast cancer can be challenging to treat. However, with the latest therapies and treatment strategies, patients have more options to treat this condition than ever before. Having a clear understanding of each individual patient’s genomic mutations is key to prescribe the most efficient drug treatments. Clinicians must balance disease control with optimal quality of life when choosing the right therapy for their patients. Finally, we are looking forward to the future where innovations could improve the efficiency of treatment even further.

Originally Post From https://www.medscape.com/viewarticle/new-approaches-treatment-hr-metastatic-breast-cancer-2024a1000c7a