The Expression And Clinical Significance Of BRCA1 In Triple Negative Breast Cancer

BackgroundIn China,along with the continuous development of diagnostic methods and molecular biology techniques,breast diseases have been recognized and followed.Breast cancer has become one of the most common malignant tumors among women,and the incidence rate has been increasing yearly.According to the data from the China Cancer Center,breast cancer has become the first killer of women,ranking first in the incidence of female malignancy,and its survival rate and recurrence rate have also gradually begun to be valued.As more and more research progresses are continuously updated,breast cancer classification methods based on ER,PR,and Her-2 are widely used worldwide,but there is a special type of breast cancer subtype— Triple negative breast cancer(TNBC)is characterized by negative expression of ER,PR,and Her-2.It is destined to be ineffective for endocrine therapy and anti-Her-2 therapy,which becomes a difficult point for treatment.Its clinical features and selection of reasonable treatment methods have become hot spots in the field of breast cancer.It is generally believed that BRCA1(breast cancer susceptibility gene 1)family mutations are important factors that cause Familial Breast Cancer Ovarian Cancer Syndrome.In recent studies,we found that BRCA1 is also associated with sporadic breast cancer,especially triple-negative breast cancers.BRCA1 is mainly found in normal human breast epithelial cell nuclear and the mutated DNA can be repaired using homologous recombination(HR).When BRCA1 tumor suppressor gene mutations occur,the expression of BRCA1 decreases or disappears.It may cause the lack of original tumor suppressor effect,and its repairing effect cannot be exerted.PurposeIn this experimental study,we used immunohistochemical(IHC)methods to detect the expression of BRCA1 protein,analyzing between the expression and the age of onset of triple negative breast cancer,tumor size,lymph node metastasis,histological grade,and the pathological stage.We also compare the expression with Ki67,P53 expression and other related parameters,and its role in the evaluation of triple negative breast cancer.Materials and MethodsA total of 63 patients with triple-negative breast cancer who underwent puncture or surgery and were pathologically confirmed were collected from Jan.to Dec.2017 in the Department of Breast Surgery at Tai'an Central Hospital.The criteria for enrollment were:(1)All patients were diagnosed with breast cancer for the first time and had not previously received antitumor therapy such as chemoradiation;(2)All patients underwent immunohistochemical examination and the results showed that ER(-)and PR(-),Her-2(-or + or ++),of which Her-2(++)patients were performed FISH test,the result was determined to be negative.Exclusion criteria:(1)Primary tumors were non-trivalent breast cancers,and local recurrences were triple-negative breast cancer patients;(2)Multicenter lesions.Paraffin-embedded specimens were collected from patients and stained with immunohistochemical SP method.The expression of BRCA1 protein was observed under microscope.The relationship between parameters related to tumor size,lymph node metastasis,histological grade,expression of Ki67,and P53 was statistically analyzed.Results1.The negative expression of BRCA1 is related to age.The negative expression rate of BRCA1 in young patients(<45 years old)is 60%,which is significantly different from that in the group older than 45 years old(P=0.020).The difference is statistically significant.2.The negative expression of BRCA1 was related to Ki67 expression.In Ki67<14% group,The negative expression rate of BRCA1 was 9.1%,while in Ki67?14% group,BRCA1 negative rate was 40.4%,P<<0.05,the difference was statistically significant.3.BRCA1 negative expression was related to P53 expression.In the P53 positive group,the negative rate of BRCA1 was 44.7%.In the P53 negative group,the BRCA1 negative rate was 20%,P=0.0017,the difference was statistically significant.4.There was no significant correlation between BRCA1 negative expression and tumor size,histological grade,lymph node metastasis and pathological stage.Conclusions1.The younger patients with TNBC have a higher rate of low expression of BRCA1.It is recommended that this group of patients should be tested for BRCA1 related genes in order to make early intervention and early screening for other patients in the family.2.The expression of BRCA1 protein was not related to tumor size,lymph node metastasis,histological grade,pathological stage,P>0.05,and the difference was not statistically significant.3.The expression of BRCA1 protein was related to the expression of Ki67.Ki67 is higher in BRCA1 negative group,suggesting that the cell proliferation activity was higher and the growth score was higher.4.The expression of BRCA1 protein is related to the expression of P53.The low expression of BRCA1 is higher in P53,associated with p53 gene mutation,and it is involved in the occurrence and development of tumors together with p53.5.BRCA1 can be used as a new assessment of breast tumors,especially TNBC indicators,to provide new ideas for solving the TNBC treatment problems.