Lipid-rich carcinoma of the breast clinicopathologic analysis of 17 cases

Abstract

Lipid-rich carcinoma of the breast is a rare variant of breast cancer, accounted for <1% of all breast malignant tumors. We retrospectively analyzed the clinicopathologic characteristics of lipid-rich carcinomas of the breast. A panel of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER-2), cytokeratin (CK) 5/6, CK14, and P63 was prepared for detection of lipid-rich carcinoma. Fluorescence in situ hybridization and electron microscope assays were performed for detecting HER-2 gene amplification and ultrastructure. Survival analysis were carried out using Kaplan-Meier and Cox regression methods. Receiver operating characteristic test was also performed. Estrogen receptor, CK5/6, CK14, and P63 were negative. Progesterone receptor (1/17) and HER-2 (17/17) were positive. HER-2 gene amplification was detected in all included cases (ratio values >2.2). Ultrastructure showed fat droplet and electron-dense material in the cytoplasm. Statistical differences were detected among survival and age (P = .033), histologic grade (P = .004), lymph node involvement (P = .001), and HER-2 expression (P = .002), respectively, using Kaplan-Meier methods. Statistical differences were also detected (P = .017) using Cox regression methods. Receiver operating characteristic test displayed significant statistical differences; the prognosis had a correlation between HER-2 expression “+” and HER-2 expression “++” (P = .004). Lipid-rich carcinoma of the breast was an HER-2 overexpressing subtype of the breast carcinoma. Survival of lipid-rich carcinoma might be associated with age, histologic grade, lymph node involvement, and HER-2. The HER-2 expression, however, might play an important role in predicting the prognosis of lipid-rich carcinoma of the breast.

Introduction

Breast cancer comprises a remarkably diverse group of diseases in presentation, morphology, molecular profile, and response to therapy. The recognition of subtypes of breast carcinomas based on their molecular features has brought new perspectives to breast cancer research [1], [2], [3], [4]. Microarray-based gene expression profiling of breast cancer has demonstrated that breast cancers can be classified into 5 main groups: luminal A, luminal B, human epidermal growth factor receptor-2 (HER-2) overexpressing, basal-like, and normal breastlike breast carcinomas according to their gene expression profiles [5], [6], [7], [8]. The HER-2 and basal-like groups were reported to have a more aggressive clinical behavior when compared with carcinomas with luminal and normal breastlike phenotypes [6], [9], [10]. Nielsen et al [6], [11] proposed an immunohistochemical panel comprising estrogen receptor (ER), epidermal growth factor receptor, HER-2, and cytokeratin (CK) 5/6, which could be used to identify breast carcinomas phenotype as defined by complementary DNA microarrays.

Lipid-rich carcinoma of the breast is a rare variant, histologic phenotype of breast cancer, accounted for <1% of all breast malignant tumors according to the World Health Organization (WHO) classification of tumors of the breast (Press, 2003). Aboumrad et al [12] first reported it as lipid-secreting mammary carcinoma. Ramos and Taylor [13] had studied it and given it a formal name. In 2003, WHO's new classification had established it as an independent type of breast cancer. As WHO classification defined, lipid-rich carcinoma of the breast is a tumor showing conspicuous amounts of vacuolated or foamy lipid in the cytoplasm, which are strongly positive when stained for neutral fat, usually very high-grade nuclear features, and a poorly differentiated growth pattern, which means few/no glands or papillae. We retrospectively analyzed 17 cases of lipid-rich carcinoma of the breast over a period of 8 years at our centers and had summarized its clinicopathologic characteristics to further recognize its biologic behavior and prognosis.