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

• Published in: Cancer medicine (Malden, MA) Vol. 13; no. 20; pp. e70336 - n/a
• Main Authors: Zhao, Zhenhui, Li, Li, He, Mei, Li, Yan, Ma, Xiaoping, Zhao, Bing
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.10.2024; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Aged; Anthracycline; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Breast carcinoma; Cancer therapies; Chemotherapy; Female; Genetic testing; Genotype & phenotype; Histology; Humans; Invasiveness; logistic regression; Lymphatic system; Metastasis; Middle Aged; Mutation; Neoadjuvant Therapy - methods; Neoplasm Staging; overall survival (OS); Patients; Platinum; platinum‐based chemotherapy; Polymorphism, Single Nucleotide; Prognosis; Prospective Studies; Remission (Medicine); single nucleotide polymorphisms (SNPs); Single-nucleotide polymorphism; Surgery; Survival; Taxanes; Treatment Outcome; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - mortality; Triple Negative Breast Neoplasms - pathology; triple‐negative breast cancer (TNBC); Tumors; X-ray Repair Cross Complementing Protein 1 - genetics; XRCC1 protein; China; platinum‐based chemotherapy; logistic regression; triple‐negative breast cancer (TNBC); single nucleotide polymorphisms (SNPs); overall survival (OS)
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.70336

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.