Parsons Heather A, Beaver Julia A, Cimino-Mathews Ashley, Ali Siraj M, Axilbund Jennifer, Chu David, Connolly Roisin M, Cochran Rory L, Croessmann Sarah, Clark Travis A, Gocke Christopher D, Jeter Stacie C, Kennedy Mark R, Lauring Josh, Lee Justin, Lipson Doron, Miller Vincent A, Otto Geoff A, Rosner Gary L, Ross Jeffrey S, Slater Shannon, Stephens Philip J, VanDenBerg Dustin A, Wolff Antonio C, Young Lauren E, Zabransky Daniel J, Zhang Zhe, Zorzi Jane, Stearns Vered, Park Ben H
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Foundation Medicine Inc., Cambridge, Massachusetts.
Clin Cancer Res. 2017 Jan 15;23(2):379-386. doi: 10.1158/1078-0432.CCR-16-1543. Epub 2016 Aug 3.
The clinical utility of next-generation sequencing (NGS) in breast cancer has not been demonstrated. We hypothesized that we could perform NGS of a new biopsy from patients with metastatic triple-negative breast cancer (TNBC) in a clinically actionable timeframe.
We planned to enroll 40 patients onto a prospective study, Individualized Molecular Analyses Guide Efforts (IMAGE), to evaluate the feasibility of obtaining a new biopsy of a metastatic site, perform NGS (FoundationOne), and convene a molecular tumor board to formulate treatment recommendations within 28 days. We collected blood at baseline and at time of restaging to assess cell-free circulating plasma tumor DNA (ptDNA).
We enrolled 26 women with metastatic TNBC who had received ≥1 line of prior chemotherapy, and 20 (77%) underwent NGS of a metastatic site biopsy. Twelve (60%) evaluable patients received treatment recommendations within 28 days of consent. The study closed after 20 patients underwent NGS, based on protocol-specified interim futility analysis. Three patients went on to receive genomically directed therapies. Twenty-four of 26 patients had genetic alterations successfully detected in ptDNA. Among 5 patients, 4 mutations found in tumor tissues were not identified in blood, and 4 mutations found in blood were not found in corresponding tumors. In 9 patients, NGS of follow-up blood samples showed 100% concordance with baseline blood samples.
This study demonstrates challenges of performing NGS on prospective tissue biopsies in patients with metastatic TNBC within 28 days, while also highlighting the potential use of blood as a more time-efficient and less invasive method of mutational assessment. Clin Cancer Res; 23(2); 379-86. ©2016 AACR.
尚未证实下一代测序（NGS）在乳腺癌中的临床应用价值。我们推测，在具有临床可操作性的时间范围内，我们能够对转移性三阴性乳腺癌（TNBC）患者的新活检样本进行NGS检测。
我们计划招募40名患者参与一项前瞻性研究“个体化分子分析指导治疗（IMAGE）”，以评估获取转移部位新活检样本、进行NGS检测（FoundationOne）以及在28天内召集分子肿瘤学专家组制定治疗建议的可行性。我们在基线期和再次分期时采集血液样本，以评估游离循环血浆肿瘤DNA（ptDNA）。
我们招募了26名接受过≥1线既往化疗的转移性TNBC女性患者，其中20名（77%）接受了转移部位活检的NGS检测。12名（60%）可评估患者在签署知情同意书后的28天内收到了治疗建议。根据方案规定的中期无效性分析，在20名患者接受NGS检测后，该研究结束。3名患者随后接受了基因组指导的治疗。26名患者中有24名在ptDNA中成功检测到基因改变。在5名患者中，肿瘤组织中发现的4个突变在血液中未被检测到，而血液中发现的4个突变在相应肿瘤中未被发现。在9名患者中，随访血液样本的NGS检测结果与基线血液样本显示100%一致。
本研究表明，在28天内对转移性TNBC患者的前瞻性组织活检样本进行NGS检测存在挑战，同时也凸显了血液作为一种更省时且侵入性更小的突变评估方法的潜在用途。《临床癌症研究》；23(2)；379 - 86。©2016美国癌症研究协会。
