Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH.
Ohio State University Comprehensive Cancer Center, Columbus, OH.
JCO Precis Oncol. 2021 Nov 24;5. doi: 10.1200/PO.21.00104. eCollection 2021.
To determine whether specific somatic copy-number alterations detectable in circulating tumor DNA (ctDNA) from patients with metastatic triple-negative breast cancer (mTNBC) are associated with sensitivity to platinum chemotherapy.
In this secondary analysis of a large cohort of patients with mTNBC whose ctDNA underwent ultralow-pass whole-genome sequencing, tumor fraction and somatic copy-number alterations were derived with the ichorCNA algorithm. Seventy-two patients were identified who had received a platinum-based chemotherapy regimen in the metastatic setting. Gene-level copy-number analyses were performed with GISTIC2.0. Cytobands were associated with progression-free survival (PFS) to platinum chemotherapy using Cox proportional hazards models. The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium data sets were interrogated for frequency of significant cytobands in primary triple-negative breast cancer (pTNBC) tumors.
Among 71 evaluable patients, 17q21 and 17q22 amplifications were most strongly associated with improved PFS with platinum chemotherapy. There were no significant differences in clinicopathologic features or (neo)adjuvant chemotherapy among patients with 17q22 amplification. Patients with 17q22 amplification (n = 17) had longer median PFS with platinum (7.0 3.8 months; log-rank = .015) than patients without 17q22 amplification (n = 54), an effect that remained significant in multivariable analyses (PFS hazard ratio 0.37; 95% CI, 0.16 to 0.84; = .02). Among 39 patients who received the nonplatinum chemotherapy agent capecitabine, there was no association between 17q22 amplification and capecitabine PFS (log-rank = .69). In The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium, 17q22 amplification occurred in more than 20% of both pTNBC and mTNBC tumors, whereas 17q21 was more frequently amplified in mTNBC relative to pTNBC (16% 8.1%, = .015).
The 17q22 amplicon, detected by ctDNA, is associated with improved PFS with platinum chemotherapy in patients with mTNBC and warrants further investigation.
确定转移性三阴性乳腺癌（mTNBC）患者循环肿瘤 DNA（ctDNA）中检测到的特定体细胞拷贝数改变是否与铂类化疗的敏感性相关。
在这项对其 ctDNA 进行超低深度全基因组测序的 mTNBC 大患者队列的二次分析中，使用 ichorCNA 算法得出肿瘤分数和体细胞拷贝数改变。确定了 72 名在转移性环境中接受铂类化疗方案的患者。使用 GISTIC2.0 进行基因水平拷贝数分析。使用 Cox 比例风险模型将细胞带与铂类化疗的无进展生存期（PFS）相关联。使用癌症基因组图谱和乳腺癌国际联合会分子分类数据集在原发性三阴性乳腺癌（pTNBC）肿瘤中检查显著细胞带的频率。
在 71 例可评估患者中，17q21 和 17q22 扩增与铂类化疗的 PFS 改善最密切相关。在 17q22 扩增的患者中，没有发现临床病理特征或（新）辅助化疗之间有显著差异。17q22 扩增患者（n = 17）的铂类化疗中位 PFS 较长（7.0 3.8 个月；对数秩 =.015），而无 17q22 扩增患者（n = 54）的中位 PFS 较短，多变量分析仍有显著意义（PFS 危险比 0.37；95%CI，0.16 至 0.84； =.02）。在 39 名接受非铂类化疗药物卡培他滨的患者中，17q22 扩增与卡培他滨 PFS 之间无关联（对数秩 =.69）。在癌症基因组图谱和乳腺癌国际联合会分子分类中，17q22 扩增发生在超过 20%的 pTNBC 和 mTNBC 肿瘤中，而 17q21 在 mTNBC 中比在 pTNBC 中更常扩增（16% 8.1%， =.015）。
ctDNA 检测到的 17q22 扩增与 mTNBC 患者铂类化疗的 PFS 改善相关，值得进一步研究。
