Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
Breast Cancer Res Treat. 2023 Jul;200(1):63-72. doi: 10.1007/s10549-023-06870-x. Epub 2023 Mar 1.
Herein, we report the frequency and distribution of germline pathogenic variants (PVs) among females with breast cancer (BC) and at least one other non-BC who underwent multi-gene panel testing (MGPT). Among females with PVs diagnosed first with BC or ovarian cancer (OC), we sought to enumerate the frequency of subsequent PV-associated cancers.
Females with BC and cancer of ≥ 1 other site (multiple primary cancers, MPC) who underwent MGPT through Ambry Genetics from March 2012 to December 2016 were included if they had testing of at least 21 genes of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53). Phenotypic data were abstracted from test requisition forms and clinical notes.
Of 6,617 evaluable patients, most were White (70.8%) and median age at first cancer, second cancer, and MGPT was 49 (interquartile range [IQR]: 18), 59 (IQR: 16), and 63 (IQR: 16) years, respectively. PVs were found among 14.1% (932/6617) of the overall cohort and in 16.4% (440/2687) of females who were diagnosed first with BC. Among those, 55.2% (243/440) had an actionable PV associated with a subsequent cancer diagnosis including 150 OCs. Of the 2443 females with breast and ovarian cancer, few (n = 97, 9.5%) were diagnosed first with OC, limiting our analysis.
Females with MPC, including BC, have a high frequency of germline PVs (14.1%). These data delineate the opportunities for intercepting subsequent cancers associated with genetic risk among females diagnosed first with BC.
本研究报告了在接受多基因panel 检测（MGPT）的乳腺癌（BC）和至少另一种非 BC 女性中，种系致病性变异（PVs）的频率和分布。在首先诊断为 BC 或卵巢癌（OC）的女性中，我们试图列举随后与 PV 相关的癌症的频率。
纳入 2012 年 3 月至 2016 年 12 月期间通过安布里遗传学接受至少 21 个感兴趣基因（ATM、BARD1、BRCA1、BRCA2、BRIP1、CDH1、CHEK2、EPCAM、MLH1、MSH2、MSH6、MUTYH、NBN、NF1、PALB2、PMS2、PTEN、RAD51C、RAD51D、STK11 和 TP53）检测的患有 BC 和≥1 种其他部位癌症（多原发癌，MPC）的女性。从检测申请表和临床记录中提取表型数据。
在 6617 例可评估患者中，大多数为白人（70.8%），首次癌症、第二次癌症和 MGPT 的中位年龄分别为 49（四分位距 [IQR]：18）、59（IQR：16）和 63（IQR：16）岁。整个队列中 14.1%（932/6617）和首先诊断为 BC 的女性中 16.4%（440/2687）发现了 PVs。其中，55.2%（243/440）有可导致后续癌症诊断的致病性变异，包括 150 例 OC。在 2443 例患有乳腺癌和卵巢癌的女性中，少数（n=97，9.5%）首先被诊断为 OC，这限制了我们的分析。
患有 MPC 的女性，包括 BC，有很高的种系 PVs 频率（14.1%）。这些数据描绘了在首先诊断为 BC 的女性中，发现与遗传风险相关的后续癌症的机会。
