Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study

Chen, Jiayi1,2; Zhu, Yingying3; Wu, Wei1,2; Xu, Yaqi1,2; Yang, Wenqian1,2; Ling, Li1,4; Lin, Qun1,2; Jia, Shijie1,2; Xia, Yuan1,2; Liu, Zihao5; Yang, Yaping1,2; Gong, Chang1,2,6

2024-02-16

10.1093/oncolo/oyae021

ONCOLOGIST   影响因子和分区

1083-7159

1549-490X

["Background As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC.Patients and methods This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis.Results In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis.Conclusion Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.","This study explored the associations between homologous recombination deficiency status and the risk of long-term prognosis of patients with HER2-low early-stage breast cancer to guide treatment decisions."]

HER2-low early breast cancer homologous recombination deficiency TCGA

SCI

英语

其他

Natural Science Foundation of China["82371739","81872139","82072907","U1911204","51861125203"] ; National Key R&D Program of China[2021YFC3001000] ; Beijing Xisike Clinical Oncology Research Foundation["Y-Roche2019/2-0078","Y-pierrefabre202102-0107"] ; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation[2020B1212060018] ; High-tech, Major and Characteristic Technology Projects in Guangzhou Area[2023P-ZD14] ; Guangzhou Science and Technology Program[202102010272] ; Fundamental Research Funds for the Central Universities, Sun Yat-sen University[2022005]

Oncology

Oncology

WOS:001163618700001

OXFORD UNIV PRESS

CLINICAL MEDICINE

Web of Science

1.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Peoples R China
2.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Dept Breast Surg, Guangzhou, Peoples R China
3.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Clin Res Ctr, Div Clin Res Design, Guangzhou, Peoples R China
4.Sun Yat Sen Univ, Sch Publ Hlth, Dept Med Stat, Guangzhou, Peoples R China
5.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Inst Resp Dis,Clin Med Coll 2,Affiliated Hosp 1,De, Shenzhen, Guangdong, Peoples R China
6.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, 107 Yanjiang West Rd, Guangzhou 510120, Peoples R China

Chen, Jiayi,Zhu, Yingying,Wu, Wei,et al. Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study[J]. ONCOLOGIST,2024,29(7).

Chen, Jiayi.,Zhu, Yingying.,Wu, Wei.,Xu, Yaqi.,Yang, Wenqian.,...&Gong, Chang.(2024).Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.ONCOLOGIST,29(7).

Chen, Jiayi,et al."Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study".ONCOLOGIST 29.7(2024).