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Abstract
Background
Germline genetic polymorphisms in certain genes are associated with the response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer (BC). This translational study aims to evaluate the potential role of rs1042713 in the beta 2-adrenergic receptor (ADRB2) gene in predicting pathological complete responses (pCRs) to taxane- and platinum-based neoadjuvant chemotherapy in locally advanced breast cancer (LABC).
Materials and methods
The distribution frequencies of rs1042713 were genotyped in LABC patients who received taxane- and platinum-based neoadjuvant chemotherapy. Associations between tumor-relevant biomarkers, genotypes and pCRs were evaluated using Student’s t-test for continuous variables and Chi-square or Fisher’s exact test for categorical variables. For univariate analysis, the relationship between the rs1042713 polymorphism and pCR was analyzed by Chi-square or Fisher’s exact test. The modified ORs with their 95% CIs were calculated by a multivariate logistic regression analysis to explore the association between genotype and pCR.
Results
There was a significant correlation of the rs1042713 genotype with estrogen receptor (ER) status (P=0.008). Significant differences were detected in the rs1042713 genotypes of pCR and non-pCR patients (P=0.046). The pCR rate was 18.2% in patients with ADRB2 rs1042713 AA genotypes and 38.7% in AG+GG genotypes. Women carrying the AG+GG (OR=2.91, 95% CI: 1.02–8.29, P=0.046) genotype had a higher pCR rate than those with the AA genotype.
Conclusion
rs1042713, which is located in the ADRB2 gene, could predict pCR to taxane-and platinum-based neoadjuvant chemotherapy in LABC. This finding suggests that rs1042713 could play a potential role as a predictive marker in clinical settings.
Acknowledgments
This research is supported by grants from the National Natural Science Foundation of China (grant numbers 81172505 and 81302302), the Doctoral Programs Foundation of the Ministry of Education of China (grant number 20120071120105), the Shanghai Natural Science Foundation (grant number 13ZR1452800), the Shanghai Municipal Commission of Health and Family Planning (grant numbers 20144Y0218, 201640006), the Science and Technology Commission of Shanghai Municipality (grant number 14411950202), the Clinical Research Plan of SHDC (grant number SHDC 12016231), the Nurturing Fund of Renji Hospital 2016 (grant number PYMDT-002) and the Nurturing Fund of Renji Hospital 2015 (grant number RJZZ15-023). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Disclosure
The authors report no conflicts of interest in this work.