Meng Shi1,2, Fei Ma3, Jibing Liu1, Huaixin Xing1, Hui Zhu4, Jinming Yu5,6, Ming Yang7. 1. Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. 2. College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. 3. Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China. 4. Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. 5. Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. sdyujinming@163.com. 6. Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. sdyujinming@163.com. 7. Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. aaryoung@yeah.net.
Abstract
PURPOSE: As a subtype of breast cancer, triple-negative breast cancer (TNBC) shows poor prognosis and high heterogeneity. Precise identification of TNBC subgroups relevant to clinical prognosis is crucial in the design and administration of individualized treatments. This study aimed to evaluate the prognostic value of the functional BRCA1 rs799917 genetic variant in TNBC. METHODS: Associations between the rs799917 polymorphism and progression risk were investigated after genotyping 370 TNBC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression. RESULTS: We found that the rs799917T allele was associated with a significantly increased risk of disease progression and shortened progression-free survival time (PFS) (P = 0.001 for log-rank test). Notably, TNBC patients with the rs799917 CC genotype showed about 22 months prolonged PFS compared to the TT genotype after radiotherapy (HR 4.44, 95% CI 1.98-9.93; P = 2.9 × 10-4). Additionally, in overweight patients, the mean PFS of the rs799917TT genotype was 10 months shorter than that of the CC genotype (HR 3.57, 95% CI 1.46-8.73, P = 0.005). CONCLUSIONS: Our findings demonstrate that the functional BRCA1 genetic variant contributes to prognosis of TNBC. Our study also highlights the clinical potential of this polymorphism in the screening of high-risk TNBC patients for recurrence and the possibility of patient-tailored decisions especially during radiotherapy.
PURPOSE: As a subtype of breast cancer, triple-negative breast cancer (TNBC) shows poor prognosis and high heterogeneity. Precise identification of TNBC subgroups relevant to clinical prognosis is crucial in the design and administration of individualized treatments. This study aimed to evaluate the prognostic value of the functional BRCA1rs799917 genetic variant in TNBC. METHODS: Associations between the rs799917 polymorphism and progression risk were investigated after genotyping 370 TNBC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression. RESULTS: We found that the rs799917T allele was associated with a significantly increased risk of disease progression and shortened progression-free survival time (PFS) (P = 0.001 for log-rank test). Notably, TNBC patients with the rs799917 CC genotype showed about 22 months prolonged PFS compared to the TT genotype after radiotherapy (HR 4.44, 95% CI 1.98-9.93; P = 2.9 × 10-4). Additionally, in overweight patients, the mean PFS of the rs799917TT genotype was 10 months shorter than that of the CC genotype (HR 3.57, 95% CI 1.46-8.73, P = 0.005). CONCLUSIONS: Our findings demonstrate that the functional BRCA1 genetic variant contributes to prognosis of TNBC. Our study also highlights the clinical potential of this polymorphism in the screening of high-risk TNBC patients for recurrence and the possibility of patient-tailored decisions especially during radiotherapy.