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

Sep 23, 2026

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Background and purpose: The prognosis for hormone receptor (HR)-positive, HER2-negative breast cancer has improved, yet many patients remain at elevated risk of recurrence. Material and methods: Narrative review of post-chemotherapy adjuvant options in HR+/HER2-breast cancer. Results: Endocrine therapy is the cornerstone; extended tamoxifen and aromatase inhibitors improve survival. Novel non-endocrine strategies include bisphosphonates, CDK4/6 inhibitors (abemaciclib, ribociclib), and olaparib for germline BRCA1/2 mutations. Interpretation: Optimal selection for toxic therapies is still unclear; future research emphasizes ctDNA monitoring, predictive biomarkers, and personalized approaches to optimize efficacy and access while limiting overtreatment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Post-chemotherapy risk stratification in HR+/HER2-breast cancer

Prognostic role of lymph node involvement and tumor size

Ki-67 and cut-off considerations

Progesterone receptor as a surrogate marker

Histological grade and histological subtype

Article metadata

REVIEW ARTICLE How to choose optimal adjuvant therapies for high-risk hormone receptor-positive, HER2-negative breast cancer after chemotherapy? Peeter Karihtalaa,b a Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Finland; bDepartment of Oncology and Radiotherapy, Oulu University Hospital, Finland 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. ARTICLE HISTORY Received 16 April 2025 Accepted 5 June 2025 Published 25 June 2025 KEYWORDS Adjuvant therapy; bisphosphonates; CDK4/6 inhibitors; disparities; endocrine treatment; PARP inhibitor Introduction Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers, commonly referred to as luminal-like breast cancers, account for 70–80% of all breast cancer cases and are a major contributor to breast cancer-related deaths, presenting a global health challenge [1–3] . Overall, their prognosis is favorable and has improved in recent decades due to earlier diagnoses and enhanced adjuvant treatments, although substantial geographical variations in prognosis still exist [4–7] . However, despite modern treatments, distant recurrences are not uncommon, and the annual risk of death from HR+/HER2-breast cancer does not plateau even after dec ades of follow-up [5, 8]. Therefore, a clear, unmet need remains for innovative strategies to reduce the recurrence rates of these cancers. The precise postoperative risk stratification is essential for planning risk-based adjuvant treatments and organizing adequate surveillance [9] . Lymph node involvement and tumor size are the most established factors predicting subsequent recurrence also in HR+/HER2- breast cancer [10, 11] . The prognostic role of Ki-67 has long been debated, primarily due to technical issues regarding analytical validity. Still, clear evidence indicates that a higher Ki-67 labeling index is associated with worse outcomes, independent of other prognostic factors [12– 14]. There is still no unequivocal consensus on the cut-off for low o

FAQs

What is the focus of the review?

The review focuses on choosing optimal post-chemotherapy adjuvant therapies for high-risk HR+/HER2-negative breast cancer and how to select patients appropriately.

Which treatments are presented as the main adjuvant options?

Endocrine therapy is described as the cornerstone, including extended tamoxifen and aromatase inhibitors, alongside additional non-endocrine options for selected high-risk patients.

How may future research improve patient selection?

The article highlights intensive research and suggests that monitoring ctDNA may enable treatment de-escalation, supported by predictive biomarkers and personalized approaches.

Sep 23, 2026

Uploaded by Melati