Clinicopathological Study Of Centrally Necrotizing Carcinoma Of The Breast

Introduction: This study aimed to investigate the clinicopathological features,immunophenotype, and biological behavior of centrally necrotizing carcinomas of the breast(CNC), and the expression of BRCA1 protein in CNC.Methods: We assessed the clinicopathological characteristics of 73 cases of CNC and30 control cases of high-grade infiltrating ductal carcinoma(IDC) with focal necrosis based on light microscopy and immunohistochemical staining for estrogen receptor,progesterone receptor, Cerb-B2/HER2, Ki-67, epidermal growth factor receptor,cytokeratin 5/6, smooth muscle actin, S-100 protein, p63, CD10 and BRCA1 protein.Results: Twenty-six of the 73 cases were examined by ultrasound, of whom 14 presented well-defined, heterogeneous, hypoechoic lesions. Mammary gland molybdenum targets were available in 30 cases, and well-defined, heterogeneous,higher-density shadows were present in 21 cases. Macroscopically, the mean tumor size was 2.49 cm(range, 1.0–6.5 cm). Unicentric, well-defined nodules were present in 67 cases, with necrosis or cystic degeneration in the central region. Microscopically, all the tumors showed extensive central necrotic or acellular zones with different degrees of fibrotic or hyaline material surrounded by ring-like or ribbon-like residual tumour tissue.The central necrotic zone accounted for >70% of the cross-sectional area of the tumor in41 cases(56.2%), >50% but <70% in 25 cases(34.2%), and >30% but <50% in seven cases(9.6%). The residual tumor was IDC grade 3 in 67 cases(91.8%). Thirty-six cases(49.3%) showed a component of ductal carcinoma in situ. The tumorous stroma around the central necrotic zone was accompanied by myxoid matrix formation in 28 cases(40%). Lymphocytic infiltration was present in 53 cases(72.6%). Granulomatous reactions were detected at the periphery of the tumors in 49 cases(67.1%). Several cases had components of mucinous carcinoma, metaplastic carcinoma, intraductal papillary carcinoma, or invasive micropapillary carcinoma. Immunohistochemistry showed greater expression of basal-like markers(72.2%, 52 cases) than myoepithelial markers(60.6%, 43 cases), both of which were significantly higher than in controls(26.7%, 8 cases)(P<0.001). According to molecular typing, most CNCs were basal-like subtype(37 cases, 50.7%), followed by luminal A(20 cases, 27.4%), luminal B(7 cases,9.6%), HER2-overexpressing(six cases, 8.2%) and null subtype(three cases, 4.1%).The expression of BRCA1 protein in CNC were lower than that of the control(P<0.05).There were no statistical significance between the expression of BRCA1 protein and ages, lymph node metastasis and tumor size of CNC(P > 0.05). The expression of BRCA1 protein in luminal A, luminal B, basal-like subtype, HER2-overexpressing and null subtype of CNC were respectively 89.5%( 17/19), 85.7%( 6/7), 52.8%(19/36),66.7%(2/4)and 0.0%(0/2)having statistical significance(P<0.05). In addition, the expression of BRCA1 protein in luminal subtype were higher than that of other subtpyes( χ 2 = 12.481, P = 0.006) and were positively associated with the expression of ER(r=0.306,P<0.05).However, the difference in clinicopathological features among groups with varying necrotic zones was not significant(P>0.05).Follow-up data were available for 28 patients, with a mean follow-up time of 21.2months(range, 7.0–40.0 months). The mean and median disease-free survivals were13.8 and 14.5 months, respectively. Disease progression occurred in 11 patients. At the last follow-up, one patient had died of breast carcinoma. The combined rate of recurrence, distant metastasis or death was significantly higher in CNC patients compared with controls(P=0.046).Conclusions:CNC as a rare type of breast, was associated with distinctive clinicopathologic features:(1)It usually occured in the elderly with high proliferative activity, highly-aggressive biological behavior, and high rates of recurrence and metastasis.( 2) Usually were well-defined unicentric nodules with necrosis or cystic degeneration in the central region.(3)Microscopically, all the tumors presented with an extensive central necrotic or acellular zones surrounded by ring-like or ribbon-like residual tumor tissue. The transition was usually abrupt in between. The residual tumor tissue were usually high-grade IDCs. The tumorous stroma was accompanied by myxoid matrix formation and lymphocytic infiltrates.( 4) The periphery of the tumor was enclosed by fibers indicating a granulomatous reaction.(5)The tumor cells possessed high proliferation activity and were mostly basal-like breast cancer.