Research Of Correlation Between Genetic Factors And Characteristics,Prognosis Of Breast Cancer

Background and Objective: 1.It is well known that tumor family history,especially breast/ovarian cancer family history is highly correlated with the risk of breast cancer.However,the correlation between tumor family history and clinicalpathological features of breast cancer is still uncertain.Our study was to evaluate the correlation of tumor family history and clinicopathological features and prognosis of breast cancer.2.BRCAness is defined as a phenotypic copy of the BRCA mutation,which describes the presence of homologous recombination defects in the same absence of BRCA germline mutations.We detected BRCAness by MLPA and explored whether BRCAness positive breast cancer has the same characteristics as the BRCA germline-associated breast cancer,and whether it can be used to predict the effectiveness of a specific treatment regimen,and the possibility of using BRCAness as a predictor of prognosis.Methods: 1.A total of 10,549 female breast cancer patients were included in this research.Collect relevant clinical pathological data and family history information.Classify patients according to family history and assess whether family history factors are associated with special breast cancer characteristics.2.For the 121 women with newly diagnosed of TNM stage I-III,MLPA method was used to classify the BRCAness of the patients' core needle biopsy specimens and/or surgical specimens.BRCA germline mutations were detected in 63 patients with high BRCA mutation risk.99 patients received taxane-based neoadjuvant chemotherapy.We assessed the correlation between BRCAness and breast cancer characteristics,chemotherapy sensitivity,and confirmed the possibility of BRCAness as a prognostic indicator.Finally we analyzed the association between BRCAness and BRCA germline mutations.Results: 1.Of the 10,549 enrolled breast cancer patients,776(7.4%)had family history of breast/ovarian cancer,2,039(19.3%)had family history of other tumors.The age of on set in other tumor family history group was significantly higher than breast cancer/ovarian cancer family history group and no tumor family history group in overall patient analysis(54.1 y vs.52.3 y vs.52.6 y,P<0.05).In breast/ovarian cancer family history subgroup analysis,the median on set age of the first-degree relatives group was significantly higher than that of the second/third relatives group(54.1 y vs.46.0 y,P<0.001).Patients with second/third-degree relatives were more likely to present with ductal carcinoma in situ(14.7% vs.6.1%,P<0.001).Patients with single breast/ovarian cancer family history were more likely to be histological grade III than patients with a family history of multiple tumors(24.6% vs.16.4%,P=0.027).There was no significant correlation between the number of affected relatives and breast cancer characteristics.At the same time,the subgroup analysis of triple negative breast cancer showed that patients with breast cancer/ovarian family history were more likely to be diagnosed at early TNM stage I,while patients with other tumor family history were more likely to be TNM stage III.Family histories of any tumor was not significantly correlated with the prognosis of triple negative breast cancer patients.2.Of the 121 patients,48(39.7%)were identified as BRCAness positive,who were more likely to be negative for hormone receptors(95.8% vs.50.7%,P<0.001),nuclear grade III(76.1% vs.48.4%,P=0.001)and triple-negative breast cancer subtype(91.6% vs.42.5%,P<0.001)than negative patients.5-year DFS(54.0% vs.88.0%,P< 0.001)and OS(76.3% vs.93.1%,P=0.002)were significantly lower in BRCAness positive group.Cox regression analysis showed that BRCAness was the independent factor for DFS(HR 3.043,95% CI 1.376 – 6.730,P=0.006)and OS(HR 2.838,95% CI 1.007 – 14.631,P=0.049).In the neoadjuvant chemotherapy subgroup analysis,the clinical response rate for taxane was significantly lower for BRCAness patients(58.3% vs.77.8%,P=0.041).BRCAness positive rate in BRCA germline mutations patients was similar as in BRCA wild-type patients(55.0% vs.58.1%,P=0.815).There was no significant difference in clinicalpathological features and porgnosis between BRCAness patients nor BRCA germline mutation patients.Conclusion: 1.Family history of other tumors and family history of breast cancer/ovarian cancer in first-degree relatives are related to the higher on set age of breast cancer.Patients with no tumor family history were more likely to present local advanced breast cancer.Triple negative breast cancer patients with breast/ovarian cancer family history were more likely to be diagnosed at early stage.And there was no significant association between tumor family history and the prognosis of triple-negative breast cancer patients.2.BRCAness is associated with higher nuclear grade,hormone receptor-negative and triple-negative breast cancer subtypes,and is less sensitive to taxane-based chemotherapy.At the same time,BRCAness can be an independent predictor for poor prognosis.There was no significant difference on clinicopathological features and prognosis between BRCA germline mutation breast cancer and BRCAness breast cancer.