Prognostic and Predictive Markers for Early Stage Triple-Negative Breast Cancer Treated With Platinum-Based Neoadjuvant Chemotherapy

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-10-24 DOI:10.1002/cam4.70336

Zhenhui Zhao, Li Li, Mei He, Yan Li, Xiaoping Ma, Bing Zhao

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Abstract

Background

Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results.

Materials and Methods

Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum-based neoadjuvant treatment. We prospectively enrolled women with stage IIB-IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline-based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease-free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled.

Results

The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3-year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS.

Conclusions

Platinum-based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline- and taxane-based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.

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早期三阴性乳腺癌铂类新辅助化疗的预后和预测指标

背景：新证据表明，铂类化疗作为浸润性导管癌三阴性乳腺癌（TNBC）的新辅助治疗可能具有疗效优势。然而，由于结果极具争议性，目前的指南尚未认可这一疗法：本研究旨在探讨XRCC1和BRCA1、BRCA2基因中的单核苷酸多态性（SNPs）对接受铂类新辅助治疗的早期TNBC患者的预测和预后作用。我们在新疆医科大学附属肿瘤医院前瞻性地招募了接受新辅助紫杉类和蒽环类化疗后病情进展的ⅡB-ⅡIB期TNBC女性患者。对肿瘤反应和病理完全反应（pCR）率进行了评估。分析了无侵袭性疾病生存期（iDFS）和总生存期（OS）。对患者的血样进行桑格测序，以确定 XRCC1 Arg194Trp 和 Arg399Gln、BRCA1 s1799949 和 BRCA2 rs206115 的基因型。采用单变量和多变量逻辑回归研究 SNPs 和临床特征与治疗反应和 pCR 之间的关系。共纳入 45 例患者：结果：该组患者的 ORR 为 44.4%，pCR 为 28.9%，中位 iDFS 为 22 个月，3 年 OS 为 73.3%。BRCA1 rs1799949的A/G和G/G基因型以及BRCA2 rs206115的T/T基因型与较高的应答率相关。组织学分级为 III 级和 Ki67 表达量大于 65% 与低反应率有关。此外，BRCA1 rs1799949的A/G基因型和BRCA2 rs206115的T/T基因型与高pCR相关。组织学 III 期和 T4 期与较差的 iDFS 相关。BRCA1 rs1799949 G/G携带者的OS最理想，A/A携带者的OS最差，A/G基因型携带者的OS居中：结论：对于蒽环类和类固醇类药物新辅助治疗耐药的TNBC患者，铂类化疗可能是一种治疗选择。我们的研究发现了一些可作为预后和预测标志物的遗传和临床特征。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.