Triple‐negative breast cancer: Histological subtypes and immunohistochemical and clinicopathological features

Abstract

To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, ''atypical'' medullary carcinoma (type A, n = 16) and carcinoma with a central acellular zone (type B, n = 11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n = 64) and special types were classified as type D (n = 5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P = 0.02), which indicates that the prognosis of type B is significantly worse than the other types. (Cancer Sci 2011; 102: 656-662) B reast cancer is a heterogeneous disease that includes various biological entities, which are separated on the basis of specific morphological and immunohistochemical features as well as clinical behavior. For many years, invasive breast cancer was classified according to its histological features and expression of hormone receptors (HR), that is, the estrogen receptor (ER) and the progesterone receptor (PR). More recently, characterization of HER2 status has become important for classifying invasive breast cancer with regard to trastuzumab treatment. Tumors that are negative for ER, PR and HER2 (triple negative [TN]) are reported to account for 12-25% of invasive breast cancer, and initially some of this group has attracted attention because of aggressive behavior and lack of response to currently available systemic therapy.(1-9)Recently, genome-wide microarray analysis has been used to classify invasive breast cancer at the transcriptional level into five main groups, which are luminal A, luminal B, normal breast-like, HER2 and basal-like.(10,11) The basal-like group includes many tumors without expression of HR and HER2, and some parts of this group show aggressive behavior and a poor prognosis.(1,3-5,8-11) Triple-negative breast cancer overlaps the profile of basal-like cancers. However, TN cancer a...

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“…Tumors with an Allred score ‡ 3 and nuclear staining of more than 10% of the tumor cells were classified as ER-positive or PR-positive (Ishikawa et al, 2011). P53 was defined as positive when more than 25% (median value) of the tumor cells were positive for nuclear staining.…”

Triple negative breast cancer: the kiss of death

“…They frequently show features of ductal invasive carcinomas [12] although metaplastic, medullary and apocrine features are also found [9, 13]. Moreover, TNBCs may present themselves as adenoid cystic lesions, histiocytoid carcinomas and even as invasive lobular carcinomas [13].…”

Ductal carcinoma in situ associated with triple negative invasive breast cancer: evidence for a precursor–product relationship

“…Few studies have described the existence of pure ductal carcinoma in situ with the basal phenotype, with Zhou et al reporting a doubled risk for local recurrence and invasion in basal-like in situ ductal carcinoma 17–21. It was suggested that an in situ component was less frequently observed in triple negative invasive breast carcinoma owing to rapid disease progression 14. More recently, Clark et al 22 documented triple negative and basal-like rates of ductal carcinoma in situ as 7.5% and 4.2%, respectively.…”