Huynh Victoria D, Mouabbi Jason, Kuerer Henry M, Wanis Kerollos Nashat, Abdel-Salam Hiam M, Gutierrez Angelica M, Johnson Helen M, Lucci Anthony, Hunt Kelly K, Arun Banu K
Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Surg Oncol. 2025 May 2. doi: 10.1245/s10434-025-17366-x.
There is a paucity of literature on germline pathogenic variants (gPVs) in patients with invasive lobular carcinoma (ILC). This study characterizes the landscape and compares clinicopathologic variables and treatment outcomes between those with and without gPVs.
A prospectively maintained institutional database was used to identify all patients diagnosed with nonmetastatic ILC who had germline genetic testing. Clinicopathologic characteristics and time to recurrence, contralateral cancer, and death were compared for patients with and without gPVs. Conditional hazard ratios, computed by Cox proportional hazards models, described associations between clinicopathologic factors, including gPV status, and cancer events.
Of 4398 patients with nonmetastatic ILC seen between 1989 and 2024, 1170 patients were evaluated by genetic counselors; 877 underwent genetic testing. 10% (83/877) had gPVs, of whom 87% (72/83) had gPVs in known breast cancer predisposition genes; 13% had gPVs in preliminary evidence genes or genes not previously known to be breast cancer associated. Patients with gPVs were more likely to be younger than 40 years, be premenopausal, have high grade and triple-negative receptor status, and undergo mastectomy compared with those without gPV (p < 0.01). At median follow-up of 80 months (interquartile range, IQR 38-135 years), there was no significant difference in the time to contralateral breast cancer, distant or local-regional recurrence, and survival among patients with and without gPVs.
In this large single-institutional analysis, patients with ILC had a distinct landscape of gPVs in breast cancer and non-breast cancer predisposition genes. A significant proportion of patients with ILC have gPVs, and these findings have potentially actionable implications.
关于浸润性小叶癌（ILC）患者种系致病性变异（gPVs）的文献较少。本研究描述了其情况，并比较了有和没有gPVs的患者的临床病理变量及治疗结果。
使用一个前瞻性维护的机构数据库来确定所有接受种系基因检测的非转移性ILC患者。比较了有和没有gPVs的患者的临床病理特征以及复发时间、对侧乳腺癌和死亡情况。通过Cox比例风险模型计算的条件风险比描述了包括gPV状态在内的临床病理因素与癌症事件之间的关联。
在1989年至2024年间就诊的4398例非转移性ILC患者中，1170例患者由遗传咨询师进行了评估；877例接受了基因检测。10%（83/877）有gPVs，其中87%（72/83）在已知的乳腺癌易感基因中有gPVs；13%在初步证据基因或先前未知与乳腺癌相关的基因中有gPVs。与没有gPVs的患者相比，有gPVs的患者更可能年龄小于40岁、处于绝经前、具有高级别和三阴性受体状态，并且接受乳房切除术（p<0.01）。在中位随访80个月（四分位间距，IQR 38 - 135年）时，有和没有gPVs的患者发生对侧乳腺癌、远处或局部区域复发以及生存时间没有显著差异。
在这项大型单机构分析中，ILC患者在乳腺癌和非乳腺癌易感基因中具有独特的gPVs情况。相当一部分ILC患者有gPVs，这些发现具有潜在的可采取行动的意义。
