染色体高度不稳定与激素受体阳性、人表皮生长因子受体 2 阴性乳腺癌患者 10 年复发风险较高有关:一项大规模、多地点、回顾性研究的临床证据。

IF 3.4 2区 医学 Q1 PATHOLOGY
Yu-Yang Liao, Jianfei Fu, Xiang Lu, Ziliang Qian, Yang Yu, Liang Zhu, Jia-Ni Pan, Pu-Chun Li, Qiao-Yan Zhu, Xiaolin Li, Wenyong Sun, Xiao-Jia Wang, Wen-Ming Cao
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引用次数: 0

摘要

激素受体阳性(HR+)和人表皮生长因子受体 2 阴性(HER2-)乳腺癌患者的长期生存期各不相同,而且转移会严重影响患者的长期生存。染色体不稳定性(CIN)是乳腺癌转移的主要驱动因素之一。在此,我们对CIN与HR+/HER2--乳腺癌患者的10年侵袭性无病生存期(iDFS)和总生存期(OS)进行了评估。在这项大规模、多地点的回顾性研究中,共招募了 354 名 HR+/HER2- 乳腺癌患者。其中,204 名患者用于内部训练,70 名用于外部验证,80 名用于交叉验证。所有病历都经过仔细审核,以获得疾病复发信息。收集福尔马林固定石蜡包埋组织样本,然后进行低通全基因组测序,使用最小 1 纳克 DNA 输入,基因组覆盖率中位数为 1.86 倍。然后使用定制的生物信息学工作流程对 CIN 进行评估。每个样本中出现三次或三次以上的 CIN 被定义为高 CIN,在内部队列中的频率为 42.2%(86/204)。高CIN与淋巴结转移、血管侵犯、孕酮受体阴性、HER2低、病理类型恶化等因素密切相关,是HR+/-乳腺癌的独立预后因素。高CIN患者的iDFS和OS均短于低CIN患者[10年iDFS为11.1%对82.2%,危险比(HR)=11.12,P<0.05]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

High chromosomal instability is associated with higher 10-year risks of recurrence for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients: clinical evidence from a large-scale, multiple-site, retrospective study

High chromosomal instability is associated with higher 10-year risks of recurrence for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients: clinical evidence from a large-scale, multiple-site, retrospective study

Long-term survival varies among hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer patients and is seriously impaired by metastasis. Chromosomal instability (CIN) was one of the key drivers of breast cancer metastasis. Here we evaluate CIN and 10-year invasive disease-free survival (iDFS) and overall survival (OS) in HR+/HER2−– breast cancer. In this large-scale, multiple-site, retrospective study, 354 HR+/HER2− breast cancer patients were recruited. Of these, 204 patients were used for internal training, 70 for external validation, and 80 for cross-validation. All medical records were carefully reviewed to obtain the disease recurrence information. Formalin-fixed paraffin-embedded tissue samples were collected, followed by low-pass whole-genome sequencing with a median genome coverage of 1.86X using minimal 1 ng DNA input. CIN was then assessed using a customized bioinformatics workflow. Three or more instances of CIN per sample was defined as high CIN and the frequency was 42.2% (86/204) in the internal cohort. High CIN correlated significantly with increased lymph node metastasis, vascular invasion, progesterone receptor negative status, HER2 low, worse pathological type, and performed as an independent prognostic factor for HR+/− breast cancer. Patients with high CIN had shorter iDFS and OS than those with low CIN [10-year iDFS 11.1% versus 82.2%, hazard ratio (HR) = 11.12, p < 0.01; 10-year OS 45.7% versus 94.3%, HR = 14.17, p < 0.01]. These findings were validated in two external cohorts with 70 breast cancer patients. Moreover, high CIN could predict the prognosis more accurately than Adjuvant! Online score (10-year iDFS 11.1% versus 48.6%, HR = 2.71, p < 0.01). Cross-validation analysis found that high consistency (83.8%) was observed between CIN and MammaPrint score, while only 45% between CIN and Adjuvant! Online score. In conclusion, high CIN is an independent prognostic indicator for HR+/HER2− breast cancer with shorter iDFS and OS and holds promise for predicting recurrence and metastasis.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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