Editor’s Note

Breast cancer is the most common malignancy in women, with an increasing incidence in recent years. HR+/HER2- breast cancer accounts for approximately 70% of all breast cancer cases, and it has a better prognosis among various subtypes. For patients with HR+/HER2- early-stage breast cancer, endocrine therapy has shown favorable survival outcomes. However, about 30% of high-risk patients experience recurrence and progress to incurable metastatic disease within 5 years after standard treatment. Several clinical studies have explored treatment options for this high-risk group, but there is still a lack of widely recognized risk assessment criteria for identifying these high-risk patients in the Chinese population. In response to this, Professor Ying Fan and the team led by Academician Xu Binghe from the National Cancer Center in China conducted a real-world study using data from the national cancer center database. The study aimed to investigate the evolving patterns of adjuvant treatment for high-risk HR+/HER2- early breast cancer patients in recent years based on clinical and pathological characteristics. The related article has been included in the 2023 ESMO Congress (Abstract No. 256P), and Professor Ying Fan from the Cancer Hospital of the Chinese Academy of Medical Sciences was invited by Oncology Frontier to present the findings.

Introduction to the Study

Patients with high-risk clinical and pathological features of HR+/HER2- early-stage breast cancer are at an increased risk of disease recurrence. The characteristics of the Chinese patient population differ significantly from Western populations, with Chinese patients being younger and a higher proportion being premenopausal. Over the past decade, there has been rapid development in the treatment strategies for these high-risk patients. Additionally, there is a lack of widely accepted risk assessment criteria in the Chinese population to identify these high-risk patients. This study represents the first use of the National Cancer Center database to investigate the evolving patterns of adjuvant treatment for early-stage breast cancer patients in China and the long-term clinical outcomes for patients with different clinical and pathological characteristics.

The study database is based on electronic medical records from 50 major hospitals in China, and patient death information was obtained through the national death registration system. The study included HR+/HER2-, stage I-III early-stage breast cancer patients who underwent curative surgery and adjuvant endocrine therapy between January 1, 2013, and March 31, 2021. Patients were stratified based on clinical and pathological features, and the research cohort was constructed. “High-risk cohort” patients had to meet one of the following criteria: ≥4 positive axillary lymph nodes or 1-3 positive axillary lymph nodes with at least one of the following high-risk clinical and pathological features: tumor tissue grade 3, tumor size ≥5 cm, or Ki-67 ≥20%. The “low-risk cohort” included patients who did not meet the above criteria. Clinical outcomes included invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS), with a statistical analysis cutoff date of September 30, 2021.

The study included a total of 4088 eligible patients, with 1310 classified as high-risk patients. Patients with ≥4 positive lymph nodes accounted for 46.6%, and those with 1-3 positive lymph nodes and high-risk clinical and pathological features accounted for 53.4%. Among the 2778 low-risk patients, 90.8% were lymph node-negative. Compared to the low-risk cohort, a higher proportion of patients in the high-risk cohort received adjuvant chemotherapy (74.9% vs. 63.7%) and radiation therapy (72.1% vs. 45.6%).

From 2013 to 2021, the proportion of patients receiving aromatase inhibitors and ovarian function suppression in adjuvant endocrine therapy gradually increased, while the use of selective estrogen receptor modulators (tamoxifen/to

moxifen) decreased. The 5-year iDFS was 75.3% for the high-risk cohort and 89.9% for the low-risk cohort. Patients in the high-risk cohort had a significantly higher risk of recurrence or death compared to the low-risk cohort, with a hazard ratio (HR) of 2.38 (95% CI: 1.82-3.12). Exploratory analysis showed that for patients with 1-3 positive lymph nodes and high-risk clinical and pathological features, the risk of disease recurrence or death gradually increased with an increase in the number of lymph nodes. Importantly, even for patients with only one positive lymph node and high-risk clinical and pathological features, the risk of disease recurrence or death was still elevated compared to low-risk patients. Similar results were observed for DRFS and OS clinical outcomes in this study.

This study suggests that nearly 25% of early-stage breast cancer patients in China with high-risk clinical and pathological features experienced recurrence or death within 5 years of starting adjuvant endocrine therapy. In recent years, the use of neoadjuvant and adjuvant therapies in HR+/HER2- early-stage breast cancer has shown promising prospects. Clinically, for some patients with high-risk clinical and pathological features, strategies involving intensified and prolonged adjuvant endocrine therapy are often employed to improve long-term survival benefits.

The study results also suggest that, for the high-risk patient population in China, despite the majority of patients adopting a “step-up” treatment strategy, such as combining endocrine therapy with chemotherapy, radiation, or adjuvant intensified ovarian function suppression, the prognosis still needs further improvement. Therefore, there is an urgent need to rethink adjuvant treatment strategies for these high-risk patients. In recent years, with the emergence of a series of new studies and drugs, such as the MonarchE and NATALEE studies using CDK4/6 inhibitors in combination with intensified adjuvant endocrine therapy, it is believed that the treatment landscape for HR+/HER2- early-stage breast cancer may undergo a new transformation to further reduce the risk of disease recurrence for patients.

Reference:

1. “Consensus on the Clinical Application of CDK4/6 Inhibitors in the Treatment of Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer”

2. Sheffield KM, et al. Future Oncol 2022;18(21):2667-2682

Cancer Hospital, Chinese Academy of Medical Sciences

Doctor of Medicine, Chief Physician of Internal Medicine, Master’s Supervisor

Visiting Scholar at the Royal Marsden Hospital/ICR in the United Kingdom (2008-2009)

Deputy Director and Secretary-General of the Clinical Research and Innovation Development Committee of the Chinese Medical Education Association

Deputy Chairman of the Youth Committee of the Chinese Anti-Cancer Association Tumor Drug Clinical Research Professional Committee

Deputy Director of the Youth Committee of the Beijing Breast Disease Prevention and Treatment Society

Deputy Director of the Youth Committee of the Beijing Cancer Prevention and Treatment Research Society

Secretary-General of the Chinese Academy of Tumor Health Management

Member of the Tumor Chemotherapy Professional Committee of the Chinese Anti-Cancer Association

Member of the Youth Committee of the Chinese Society of Clinical Oncology

Published numerous articles in domestic and international journals, including JAMA Oncology, Annals of Oncology, etc.