Clinicopathologic Analyses of 34 Cases of High-Grade Serous-Like Carcinoma (HG-SL-Ca) of the Breast

High-grade serous-like carcinoma (HG-SL-Ca) of the breast is a newly recognized entity. We present the largest series with 34 cases. Inclusion criteria were breast carcinoma with ≥70% areas showing discordant well-formed tubules and high nuclear grade. Twenty-four (70.6%) were triple negative; 5 (14.7%) were ER+/HER2-; 2 (5.9%) were ER+/HER2+; and 3 (8.8%) were ER-/HER2+. Axillary lymph node metastasis was seen in 10 (31.3%) of 32 cases. Nine patients had neoadjuvant chemotherapy and 2 (22.2%) achieved pathologic complete response (pCR). Of the 32 patients with available follow-up data, 2 (6.3%) had local recurrence; 6 (18.8%) had distant metastasis; and 1 (3.1%) had both local recurrence and metastasis; 6 (18.8%) died of disease. Univariate analysis showed that only larger tumor size (P=0.04) was associated with shorter metastasis-free survival; and larger tumor size (P=0.003) and higher percentage of serous-like pattern (P=0.03) were associated with worse overall survival. 27 (81.8%) of 33 cases had aberrant p53 expression; 16 (64.0%) of 25 showed p16 block positivity; 26 (86.7%) of 30 showed at least focal GATA-3 staining; 25 (89.3%) of 28 were negative for nuclear WT1 (3 had focal staining); and 28 (96.6%) of 29 were negative for PAX-8 (1 had focal staining). HG-SL-Ca of the breast has distinct morphology and the majority show aberrant p53 expression. Patients showed a low pCR rate and poor outcomes. The distinct morphology, immunohistochemistry (IHC) profile and clinical presentations warrant classifying these tumors as a new entity. The morphologic features and IHC studies can help differentiate breast HG-SL-Ca from other carcinomas.