使用循环肿瘤 DNA（ctDNA）分析年轻和老年晚期乳腺癌患者的突变谱差异。

Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA).

机构信息

Washington University, 660 South Euclid Avenue, Campus Box 8056, Saint Louis, MO, 63110, USA.

Guardant Health, Redwood City, CA, USA.

出版信息

Breast Cancer Res Treat. 2021 Feb;185(3):639-646. doi: 10.1007/s10549-020-06019-0. Epub 2020 Nov 20.

DOI:10.1007/s10549-020-06019-0

PMID:33219484

Abstract

PURPOSE

Little is known regarding the mutation profiles of ctDNA in the older adult breast cancer population. The objective of this study is to assess differences in mutation profiles in the older adult breast cancer population using a ctDNA assay as well as assess utilization of testing results.

METHODS

Patients with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360) between 5/2015 and 10/2019 at Siteman Cancer Center. The profiling results of a multi-institutional database of patients with advanced breast cancer who had undergone molecular profiling were obtained. Associations between mutations and age group (≥ 65 vs. < 65) were examined using a Fisher's exact test.

RESULTS

In the single-institutional cohort, 148 patients (69.2%) were < 65 years old and 66 patients (30.8%) ≥ 65 years old. ATM, BRAF, and PIK3CA mutations were found more frequently in older patients with ER + HER2- breast cancers (p < 0.01). In the multi-institutional cohort, 5367 (61.1%) were < 65 years old and 3417 (38.9%) ≥ 65 years old. ATM, PIK3CA, and TP53 mutations were more common in the older cohort (p < 0.0001) and MYC and GATA3 mutations were less common in the older cohort (p < 0.0001). CtDNA testing influenced next-line treatment management in 40 (19.8%) patients in the single-institutional cohort.

CONCLUSION

When controlling for subtype, results from a single institution were similar to the multi-institutional cohort showing that ATM and PIK3CA were more common in older adults. These data suggest there may be additional molecular differences in older adults with advanced breast cancers.

摘要

目的

关于老年乳腺癌患者 ctDNA 的突变谱知之甚少。本研究的目的是使用 ctDNA 检测评估老年乳腺癌患者的突变谱差异，并评估检测结果的应用。

方法

2015 年 5 月至 2019 年 10 月，在 Siteman 癌症中心，采用基于血浆的 ctDNA NGS 检测（Guardant360）对晚期乳腺癌患者进行分子谱分析。获得了在分子谱分析中接受过检测的多机构晚期乳腺癌患者的谱分析结果。采用 Fisher 精确检验分析突变与年龄组（≥65 岁与<65 岁）之间的关系。

结果

在单机构队列中，148 例（69.2%）患者年龄<65 岁，66 例（30.8%）患者年龄≥65 岁。在 ER+HER2-乳腺癌老年患者中，ATM、BRAF 和 PIK3CA 突变更为常见（p<0.01）。在多机构队列中，5367 例（61.1%）患者年龄<65 岁，3417 例（38.9%）患者年龄≥65 岁。在老年队列中，ATM、PIK3CA 和 TP53 突变更为常见（p<0.0001），而 MYC 和 GATA3 突变更为少见（p<0.0001）。在单机构队列中，40 例（19.8%）患者的 ctDNA 检测结果影响了后续治疗管理。