Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer
ONCOLOGY LETTERS
Authors: Zhu, Lizhe; Ma, Nan; Wang, Bin; Zhou, Can; Yan, Yu; Wang, Ke; He, Jianjun; Ren, Yu
Abstract
The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2(-) early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the (2) test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar (2) test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2-47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase II (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin 3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.
RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRCA1, TUBB3 and RRM1 in NSCLC
LUNG CANCER
Authors: Vilmar, A.; Garcia-Foncillas, J.; Huarriz, M.; Santoni-Rugiu, E.; Sorensen, J. B.
Abstract
Background: Customized chemotherapy is increasingly used in the management of patients with advanced non-small cell lung cancer (NSCLC). However, the most reliable methodology to determine biomarker status is neither fully elucidated nor agreed upon. Accordingly, we evaluated the predictive efficiency of qRT-PCR and immunohistochemical analysis (IHC) on excision cross complementation group 1 (ERCC1), breast cancer susceptibility gene 1 (BRCAI), ribonucleotide reductase subunit M1 (RRM1) and class III beta-tubulin (TUBB3). Patients and methods: IHC and qRT-PCR on ERCC1, BRCA1, RRM1 and TUBB3 were performed on surgically resected tissue samples from NSCLC-patients included in a randomized trial. The median values of the biomarker expression dichotomized the population and were correlated to clinical endpoints. Results: Representative tissue samples from 33 patients showed no significant correlations between mRNA and protein expression. Predictive impact was demonstrated for all four biomarkers, when assessed by IHC, and reached significance for overall survival in patients with ERCC1-negative (14.3 vs. 8.5 months, p=0.018) and TUBB3-negative (18.5 vs. 11.10, p = 0.027) tumours, while this was not the case for qRT-PCR. Conclusions: IHC discriminated more effectively than qRT-PCR across four NSCLC-relevant biomarkers. The findings are further supported by the demonstrated lack of correlation between transcript and protein. (C) 2011 Elsevier Ireland Ltd. All rights reserved.