Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 676 North St. Clair, Suite 880, Chicago, IL, 60611, USA.
Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH, USA.
Breast Cancer Res Treat. 2017 Nov;166(1):179-184. doi: 10.1007/s10549-017-4415-1. Epub 2017 Jul 27.
Genomic profiling can identify targetable mutations; however, the impact of tissue-based genomic profiling on clinical decision making for patients with metastatic breast cancer has not been well characterized.
Patients with stage IV breast cancer who had undergone genomic profiling between 7/2013 and 3/2015 were identified at three academic cancer centers. Genomic analysis was determined to have impacted clinical decision if (A) a patient was enrolled onto a genotype-matched clinical trial or (B) prescribed off-label an FDA-approved therapy targeting an identified mutation. The frequency of mutated genes was determined.
A total of 117 patients with stage IV breast cancer were identified. Median age was 46 (25-75). Fifty-three patients (45%) had ER-positive/HER2-negative disease, 50 (43%) had ER-negative/HER2-negative disease, and 14 (12%) had ER-any/HER2-positive disease. Median number of previous therapies received prior to genomic profiling was 2 (range 0-15), and median follow-up after testing was obtained after 5.8 months (range 0-24.4 months). Commercial reports indicated that 85 (73%) patients had at least one mutation targetable by an FDA-approved medication, and 112 (96%) patients had at least one clinical trial available; however, clinical management was only affected in 11 patients (9%). The most frequent mutations observed were those in TP53, FGF, PI3KCA, MYC, ZNF, FGFR, CCND, ARID1A, GATA3, and MAP; frequencies of these mutations varied by clinical subtype.
Tumor genomic profiling affected clinical management in a minority of patients with metastatic breast cancer, thus these data do not support the routine use of genomic profiling outside of a clinical trial.
基因组分析可以鉴定出可靶向的突变；然而，组织基因组分析对转移性乳腺癌患者的临床决策的影响尚未得到很好的描述。
在三个学术癌症中心，确定了在 2013 年 7 月至 2015 年 3 月期间进行基因组分析的 IV 期乳腺癌患者。如果 (A) 患者入组到与基因匹配的临床试验中，或 (B) 处方针对鉴定出的突变的 FDA 批准的治疗药物，则认为基因组分析对临床决策有影响。确定突变基因的频率。
共确定了 117 例 IV 期乳腺癌患者。中位年龄为 46 岁（25-75 岁）。53 例（45%）患者为 ER 阳性/HER2 阴性疾病，50 例（43%）患者为 ER 阴性/HER2 阴性疾病，14 例（12%）患者为 ER 阳性/HER2 阳性疾病。在进行基因组分析之前，中位数接受的治疗次数为 2 次（范围 0-15 次），在测试后中位数随访时间为 5.8 个月（范围 0-24.4 个月）。商业报告表明，85 例（73%）患者至少有一种可通过 FDA 批准药物治疗的突变，112 例（96%）患者至少有一种临床试验可供选择；然而，只有 11 例（9%）患者的临床管理受到影响。观察到的最常见突变是 TP53、FGF、PI3KCA、MYC、ZNF、FGFR、CCND、ARID1A、GATA3 和 MAP 中的突变；这些突变的频率因临床亚型而异。
肿瘤基因组分析仅影响少数转移性乳腺癌患者的临床管理，因此这些数据不支持在临床试验之外常规使用基因组分析。
