Editor's Note: At the highly anticipated 2024 San Antonio Breast Cancer Symposium (SABCS), numerous groundbreaking studies in breast cancer treatment were unveiled. Among them, the Working Group for Gynecological Oncology (WSG) presented long-term survival data from the WSG ADAPT-HR+/HER2- early breast cancer chemotherapy cohort (Abstract No.: GS3-04). This study integrates clinical pathology, genomic testing, and endocrine therapy response to refine risk stratification for recurrence in HR+/HER2- patients. Oncology Frontier invited Dr. Jia Wang from The Second Affiliated Hospital of Dalian Medical University to provide insights and commentary on this significant research.

Study Title

Endocrine Therapy (ET) Response-Guided (Neo)Adjuvant Weekly nab-Paclitaxel vs. Biweekly Solvent-Based Paclitaxel Followed by Biweekly EC in Genomic or Clinically High-Risk HR+/HER2- Early Breast Cancer: Final Survival Results from the WSG ADAPT-HR+/HER2- Chemotherapy Trial

Dr. Jia Wang：Optimizing treatment strategies for high-risk HR+/HER2- early breast cancer remains an ongoing challenge. Key unresolved questions include:

1. Defining “High Recurrence Risk”: A comprehensive risk assessment should integrate clinical, pathological, genomic, and drug sensitivity data.
2. Identifying Beneficial Subgroups: Which patient subgroups truly benefit from chemotherapy, and what are the optimal regimens?
3. pCR as a Surrogate for Long-Term Survival: Does achieving pCR through neoadjuvant chemotherapy translate into improved long-term outcomes?
4. Role of Enhanced Endocrine Therapy: Can targeted therapies like CDK4/6 inhibitors replace chemotherapy in this patient population?

The WSG-ADAPT series has provided critical evidence supporting chemotherapy de-escalation in selected populations. The latest survival data presented at SABCS 2024 underscore several key design aspects:

• Patient Selection: Three groups were included: (1) Clinically low-risk but genomically intermediate-risk with poor ET response, (2) Clinically low-risk but genomically high-risk, and (3) Clinically ultra-high-risk patients without RS or ET assessment.
• Chemotherapy Regimens: Both arms used dose-dense anthracycline-taxane regimens, comparing weekly nab-PAC with biweekly sb-PAC.
• Five-Year Survival as Primary Endpoint.

Notable Findings:

• Patients with N0-1 and RS <25 had excellent prognosis without chemotherapy (5-year dDFS >96%).
• Dynamic Ki-67 changes reflecting ET response are independent prognostic indicators.
• High RS (>25) correlates with higher pCR, particularly in ET non-responders.
• Dense anthracycline-taxane regimens provide robust survival benefits, with nab-PAC outperforming sb-PAC in ET non-responders.

In conclusion, future risk stratification for HR+/HER2- breast cancer should integrate clinical factors, genomic scores, and short-term ET response. For high-risk patients requiring chemotherapy, intensive anthracycline-taxane regimens remain effective. Whether chemotherapy can be replaced by intensified endocrine therapy, such as combining with CDK4/6 inhibitors, awaits results from the ADAPTcycle study.

Dr. Jia Wang

• Chief Physician, Professor, Master’s Supervisor
• MD, Postdoctoral Fellow
• Deputy Director, Breast Surgery, Second Affiliated Hospital of Dalian Medical University
• Member, Breast Group, Chinese Medical Association Oncology Branch
• Committee Member, Chinese Anti-Cancer Association Breast Cancer Division
• Executive Member, Chinese Anti-Cancer Association Breast Cancer Screening Committee
• Standing Member, Liaoning Medical Association Breast Surgery Branch
• Deputy Chair, Breast Cancer Precision Treatment and Clinical Research Committee, Liaoning Society for Cell Biology