BackgroundTo determine the histopathological and MRI features of BRCA1/2 mutation-associated familial breast cancers compared with those of BRCA1/2 mutation-negative and sporadic breast cancers and to further compare the imaging features of cancers from BRCA1 and BRCA2 mutation carriers according to lesion type on MRI.MethodsA retrospective review of medical records was conducted to determine tumour clinicopathologic features and MRI characteristics between June 2011 and July 2017, and 93 lesions with BRCA mutations, 93 lesions without BRCA mutations from familial breast cancers and 93 lesions from sporadic breast cancers were included. Histopathologic data, including immunohistochemistry findings and MRI data according to the BI-RADS lexicon, were reviewed. The association between MRI or histopathologic findings and BRCA mutations was analysed.ResultsBRCA-positive familial breast cancers had a higher number of IDCs with high nuclear grade and lymph node metastasis (all P<0.05), while the BRCA-negative group had a significantly lower Ki-67 index (P<0.001). BPE on MRI was found to be significantly lower for BRCA mutations of familial breast cancer (P=0.024). BRCA1 carriers tended to exhibit the triple-negative phenotype with a more benign shape and margin (P=0.006 and 0.019), whereas BRCA2 mutations were associated with the luminal phenotype and more malignant features.ConclusionsBRCA mutation carriers had a significantly higher number of IDCs with more aggressive cancer, and BRCA-negative cancers had low proliferation levels. Background features on MRI may help to identify BRCA status, while tumour characteristics can differentiate the BRCA1/2 mutation status, consistent with the differences in their clinicopathologic features.

Background and purpose: BRCA1 and BRCA2 are two most common genes associated with hereditary breast cancers. Our research intended to discover the pathologic features of Chinese breast cancers with BRCA1/2 mutations. Methods: We included 287 breast cancers between 2011 and 2017, and BRCA1/2 germline mutation tests were carried out. The pathologic features of each patient were collected at Department of Pathology in Fudan University Shanghai Cancer Center for comparative study. Results: Of the 287 breast cancers, 66 cases were BRCA1 mutation positive, 47 cases were BRCA2 mutation positive and 174 cases were BRCA1/2 mutation negative. BRCA1 mutation breast cancer had higher nuclear grade tumors than the other two groups (P<0.001), 72.7% of BRCA1 mutation breast cancers were, whereas 25.5% of BRCA2 and 19.0% of non-BRCA1/2 mutation breast cancers were triple negative (P<0.001). BRCA1 and BRCA2 mutated breast cancers had lower human epidermal growth factor receptor 2(HER2) expression than non-BRCA1/2 mutated breast cancers (P<0.001). The positive expressions of cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR) in BRCA1 mutation breast cancer were about 50%, significantly higher than those of the other two groups (P<0.001), and androgen receptor (AR) positive was less frequently seen in BRCA1 mutation breast cancers. Conclusion: These results suggest that BRCA1 mutation-associated breast cancers had clinical pathologic characteristics, such as triple negative, more positive CK5/6 or EGFR status. BRCA1/2 mutated breast cancers had lower HER2 expression.

Purpose: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. Methods: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. Results: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. Conclusion: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.