Dejaegher Kwinten, Nevelsteen Ines, Han Sileny, Verhoeven Jelle, Wildiers Hans, Punie Kevin
Department of General Medical Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, Louvain, Belgium.
Department of Oncological Surgery, Multidisciplinary Breast Center, University Hospitals Leuven, Louvain, Belgium.
Fam Cancer. 2025 Jun 12;24(2):54. doi: 10.1007/s10689-025-00478-4.
Limited data exist on hereditary breast cancer characteristics and treatment driven by germline mutations beyond BRCA. Our primary aim is to describe the tumour and patient characteristics, treatment patterns and outcomes in patients with non-BRCA hereditary breast cancer with a focus on CHEK2, ATM, PALB2 and TP53 variants. This is a retrospective single centre hospital-based cohort study of adult patients with a known (likely) pathogenic germline mutation and breast cancer diagnosis in UZ Leuven before April 2022. Data collection included baseline demographics, breast cancer characteristics, treatment patterns and disease outcome variables. Cohorts of patients with variants in different genes will be compared. We retrieved 185 patients with variants in ATM (N = 40), CHEK2 (N = 114), PALB2 (N = 8) and TP53 (N = 23). Median age was significantly lower in the TP53 group (36 years, p = 0.001). Only estrogen receptor (ER) status (p = 0.005) and breast cancer subtype (p < 0.001) differed significantly across the defined gene cohorts. HER2-positive disease was more frequent in the TP53 subgroup (59.1%, p < 0.001). Neoadjuvant chemotherapy was more commonly administered in the PALB2 and TP53 cohorts (p = 0.011). Univariate and multivariate survival analysis by gene cohort showed no significant difference in survival outcomes. In our series, we confirm that TP53 carriers are younger at breast cancer diagnosis and have more often HER2-positive breast cancer. Triple-negative breast cancer is more frequent in the PALB2 carriers, while ER-positivity is most common in ATM and CHEK2 carriers. Survival outcomes were similar across different gene cohorts in this study.
关于除BRCA之外的种系突变驱动的遗传性乳腺癌特征和治疗的数据有限。我们的主要目的是描述非BRCA遗传性乳腺癌患者的肿瘤和患者特征、治疗模式及预后，重点关注CHEK2、ATM、PALB2和TP53变异。这是一项基于鲁汶大学医院的回顾性单中心队列研究，研究对象为2022年4月前确诊为已知（可能）致病性种系突变和乳腺癌的成年患者。数据收集包括基线人口统计学、乳腺癌特征、治疗模式和疾病转归变量。将对不同基因变异患者队列进行比较。我们检索到185例患者，其中ATM变异40例、CHEK2变异114例、PALB2变异8例、TP53变异23例。TP53组的中位年龄显著更低（36岁，p = 0.001）。在定义的基因队列中，仅雌激素受体（ER）状态（p = 0.005）和乳腺癌亚型（p < 0.001）存在显著差异。TP53亚组中HER2阳性疾病更为常见（59.1%，p < 0.001）。新辅助化疗在PALB2和TP53队列中更常用（p = 0.011）。按基因队列进行的单因素和多因素生存分析显示生存结局无显著差异。在我们的系列研究中，我们证实TP53携带者在乳腺癌诊断时更年轻，且更常患HER2阳性乳腺癌。三阴性乳腺癌在PALB2携带者中更常见，而ER阳性在ATM和CHEK2携带者中最常见。本研究中不同基因队列的生存结局相似。
