Editor’s Note: HR+/HER2- is the most common subtype of breast cancer, accounting for approximately 65% to 70% of all breast cancer cases. Improving the survival benefits for patients with advanced HR+/HER2- breast cancer has always been a hot topic in this field and a unanimous goal for scholars and experts. Exploring the genomic characteristics of advanced HR+/HER2- breast cancer can enhance our understanding of it, and even identify potential biomarkers that affect its treatment and prognosis. The team led by Professor Li Huiping from the Peking University Cancer Hospital conducted a comprehensive genomic analysis of advanced HR+/HER2- breast cancer patients using liquid biopsy technology. Their research results were included as a poster (abstract number: 496P) at this year’s ESMO conference. Oncology Frontier has specially invited Professor Shao Bin to introduce the latest results of this study.
Research Background:
Breast cancer is the most common malignant tumor affecting women worldwide. In 2020, there were over 2.26 million new cases and more than 680,000 deaths reported. The most common type of breast cancer is HR+/HER2- breast cancer, which has a complex genomic landscape and requires comprehensive genomic analysis. However, performing tissue biopsies on patients with recurrent metastases is challenging. Moreover, only a few studies have used liquid biopsy, and these studies are unable to detect gene copy number loss. In this study, the research team conducted a comprehensive genomic analysis of advanced HR+/HER2- breast cancer patients using liquid biopsy.
Research Method:
This retrospective study recruited 76 patients with advanced HR+/HER2- breast cancer, of whom 37 received chemotherapy as first-line treatment, and 39 received palbociclib combined with endocrine therapy. Plasma samples from these patients were collected before they underwent chemotherapy and CDK4/6 inhibitor treatment. The study employed PredicineCARE, a next-generation sequencing (NGS) liquid biopsy technology from Huidu Medical, to detect somatic changes in circulating tumor DNA (ctDNA) in the blood, including single nucleotide variations (SNV), gene fusions, and copy number variations (CNV).
Research Results:
In this study, 370 somatic mutations and 85 copy number variations (CNVs) were detected in the plasma samples. The most common altered genes included TP53 (37%), PIK3CA (37%), ESR1 (21%), RAD50 (21%), ATM (18%), FGFR1 (17%), CDH1 (16%), and BRCA2 (14%).
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Additionally, the research team further explored the correlation between patients’ genetic alterations and their clinical-pathological characteristics. Of the 76 patients, 27 showed low expression of Ki67, 43 had high expression, and the Ki67 status was unknown in 6 patients. The occurrence of DNA damage repair-related gene (NBN) mutations was significantly higher in the high Ki67 expression group compared to the low expression group (High Ki67 expression group: 8/43 vs. Low Ki67 expression group: 0/27, P<0.05). Of the 76 patients, 17 had metastases at initial diagnosis, and the rate of FAT1 mutations was significantly higher in the metastatic group compared to non-metastatic patients (Metastatic group: 10/17 vs. Non-metastatic group: 7/59, P<0.05).
Among the 76 patients, 39 received CDK4/6 inhibitor treatment, and 37 underwent chemotherapy. The research team followed up with both groups of patients. Although the median overall survival (mOS) for both groups had not been reached during the follow-up period, patients who received CDK4/6 inhibitor treatment had a significantly prolonged OS compared to those who received chemotherapy (P<0.001). However, there was no significant difference in progression-free survival (PFS) between the two groups; the median PFS for the chemotherapy group was 16.0 months, and for the CDK4/6 inhibitor group, it was 15.8 months.
Research Conclusion:
This study conducted a genetic profiling of 76 HR+/HER2- advanced breast cancer patients using liquid biopsy, reflecting the overall genetic alterations in such patients, while also exploring the correlation between genomic alterations and clinical-pathological characteristics. The final analysis of this study has not yet been conducted. In the future, the research team will further analyze the correlation between survival characteristics and genetic alterations in patients with different clinical features receiving different treatments, thereby identifying potential prognostic biomarkers and targeted therapies.
Professor Bin Shao
- Department of Breast Oncology, Peking University Cancer Hospital
- Academic Director of the Breast Center, Peking University Cancer Hospital Inner Mongolia Hospital
- Associate Chief Physician, Associate Professor
- Expertise: Comprehensive treatment of breast cancer involving precision therapy, chemotherapy, endocrine therapy, targeted therapy, and immunotherapy. Specializes in treating recurrent, resistant, and difficult breast cancers of different types: HER2-positive, triple-negative, hormone receptor-positive, and various metastatic forms including liver, brain, lung, bone, chest wall metastases, pleural effusion, and pericardial effusion, as well as managing side effects.
- Visiting Scholar at MD Anderson
- Member of the Youth Committee of the Chinese Medical Association’s Breast Tumor Group
- Secretary-General and Deputy Director of the Breast Cancer Expert Committee of the Beijing Health Promotion Association
- Standing Committee Member of the Breast Cancer Expert Committee of the China Health Promotion Foundation
- Standing Committee Member of the Breast Disease Subcommittee of the China Medical Promotion Association
- Standing Committee Member of the Oncocardiology Expert Committee of the Beijing Health Promotion Association
- Supervisor of the Beijing Gonadal Axis Disease Prevention and Treatment Research Society
- Committee Member of the Beijing Breast Disease Prevention and Treatment Society
- Member of the Precision Targeted Diagnosis and Treatment Professional Committee of the Beijing Cancer Prevention and Treatment Association
- Member of the Breast Cancer Committee of the Beijing Cancer Prevention and Treatment Society
