How to choose optimal adjuvant therapies for high-risk hormone receptor-positive, HER2-negative breast cancer after chemotherapy?

Abstract

Background and purpose: The prognosis for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer has significantly improved over the past few decades. However, a substantial number of patients still face an elevated risk of recurrence. Due to the high prevalence and cumulative mortality of HR+/HER2- breast cancer, it poses a global health challenge.

Material and methods: This is a narrative review on the post-chemotherapy treatment options in patients with HR+/HER2- breast cancer.

Results: Endocrine therapy remains the cornerstone of adjuvant treatment, with extended durations of tamoxifen and aromatase inhibitors demonstrating survival benefits. Several novel post-chemotherapy adjuvant treatments have recently been introduced for high-risk patients, and now most patients with HR+/HER2- breast cancer are eligible for non-endocrine adjuvant therapies. Bisphosphonates help to reduce bone recurrence and enhance overall survival in postmenopausal women, though the evidence remains somewhat inconsistent. CDK4/6 inhibitors abemaciclib and ribociclib have also emerged as adjuvant therapies, while the poly ADP ribose polymerase (PARP) inhibitor olaparib provides clinically meaningful benefits for patients with germline BRCA1/2 mutations.

Interpretation: Optimal patient selection for these often toxic treatments remains partially unclear and is the focus of intensive research. In the near future, monitoring ctDNA may enable treatment de-escalation for selected high-risk patients. The rise of perioperative immunological therapies, new CDK4-specific inhibitors, and targeted endocrine treatments can lead to a notably favorable prognosis for many previously high-risk HR+/HER2- breast cancers. Future research should prioritize predictive biomarkers and personalized approaches to optimize treatment efficacy, ensure more equal access to treatments, and minimize overtreatment.