Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer

IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Monika Drobniene , Dominyka Breimelyte , Ieva Sadzeviciene , Rasa Sabaliauskaite , Ruta Barbora Valkiuniene , Raimundas Meskauskas , Daiva Dabkeviciene , Sonata Jarmalaite
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引用次数: 0

Abstract

Background

The rate of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC) varies, and adjuvant therapy treatment for residual cancer remains a challenge. The aim of our study was to assess the added value of FoundationOne®CDx (F1CDx) testing in the non-metastatic TNBC in predicting responses to NACT and disease outcomes.

Methods

Ninety-three eligible patients with stage II-III TNBC were treated with NACT without immunotherapy. Response to NACT was evaluated postoperatively. Comprehensive genomic profiling with NGS-based molecular test F1CDx was performed on diagnostic biopsies (N = 93). Hierarchical clustering and logistic regression were applied for data analysis.

Results

Genomic profiling and data clustering revealed heterogeneous genetic landscapes of TNBC with subsets displaying multilayered co-amplifications of oncogenes and overlapping changes in crucial signaling pathways. TP53 mutations were detected in 95 % of all TNBCs. BRCA1/BRCA2 mutations were significant molecular factors in predicting favorable responses to NACT (OR = 0.09, p = 0.002), while CCNDs co-mutations with FGFs (OR = 13.4, p = 0.016) and PI3Ks family mutations in AR-positive cases (OR = 6.1, p = 0.008) – poor responses. Low tumor mutational burden (TMB) ≤ 3 (OR = 9.4, p = 0.009) was a significant factor for the disease progression after NACT.

Conclusions

This study suggests that comprehensive CDx testing can be explored as a prognostic tool in early-stage TNBC to predict responses to NACT and disease progression. Based on these results, genomic analysis should be performed early in the patient journey, possibly guiding adjuvant treatment choices and participation in randomized clinical trials, mainly when pCR is not achieved, as the ultimate goal is improving patient outcomes.
全面的基因组分析可以预测三阴性乳腺癌对新辅助化疗的反应
背景三阴性乳腺癌(TNBC)新辅助化疗(NACT)后的病理完全缓解(pCR)率各不相同,残留癌的辅助治疗仍然是一个挑战。本研究的目的是评估FoundationOne®CDx (F1CDx)检测在非转移性TNBC中预测NACT反应和疾病结局的附加价值。方法93例II-III期TNBC患者采用NACT治疗,不采用免疫治疗。术后评估NACT的疗效。诊断活检采用基于ngs的分子检测F1CDx进行全面基因组谱分析(N = 93)。采用层次聚类和逻辑回归对数据进行分析。结果基因组分析和数据聚类揭示了TNBC的异质性遗传景观,其中亚群显示癌基因的多层共扩增和关键信号通路的重叠变化。在95%的tnbc中检测到TP53突变。BRCA1/BRCA2突变是预测NACT良好反应的重要分子因素(OR = 0.09, p = 0.002),而CCNDs与FGFs共突变(OR = 13.4, p = 0.016)和ar阳性病例中pi3k家族突变(OR = 6.1, p = 0.008) -不良反应。低肿瘤突变负荷(TMB)≤3 (OR = 9.4, p = 0.009)是NACT后疾病进展的重要因素。结论:综合CDx检测可作为早期TNBC的预后工具,预测NACT的反应和疾病进展。基于这些结果,基因组分析应该在患者早期进行,可能指导辅助治疗的选择和参与随机临床试验,主要是在没有实现pCR的情况下,因为最终目标是改善患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Breast
Breast 医学-妇产科学
CiteScore
8.70
自引率
2.60%
发文量
165
审稿时长
59 days
期刊介绍: The Breast is an international, multidisciplinary journal for researchers and clinicians, which focuses on translational and clinical research for the advancement of breast cancer prevention, diagnosis and treatment of all stages.
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