Differential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without Paclitaxel

Abstract

BackgroundThe aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC).Materials and MethodsFormalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5), and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67low); luminal B (ER/PgR-positive, HER2-negative, Ki67high); luminal-HER2 (ER/PgR-positive, HER2-positive); HER2-enriched (ER-negative, PgR-negative, HER2-positive); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive).ResultsAfter a median follow-up time of 105.4 months the 5-year disease-free survival (DFS) and overall survival (OS) rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively) for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31–2.80, Wald's p = 0.001) and for death 2.53 (95% CI: 1.62–3.60, p<0.001). Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors.ConclusionsTriple-negative phenotype is of adverse prognostic value for DFS and OS in patients treated with adjuvant dose-dense sequential chemotherapy. In the pre-trastuzumab era, the HER2-enriched subtype predicts favorable outcome following paclitaxel-containing treatment.

A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer

“…[3] The data showed there were more patients with Luminal B breast cancer than Luminal A disease. [910] Luminal B breast cancer is complicated, and the patients were divided into two subgroups based on status: HER2-positive and HER2-negative. This study enrolled only patients with Luminal B HER2-negative breast cancer to avoid the interference of nonregular trastuzumab administration in HER2-positive patients in China.…”

TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting

“…Low-density TMA blocks carried 2 × 1.5 mm cores from different areas of each tumor. All tumors were clinically subtyped with ER/PgR/HER2/Ki67 IHC and FISH, as previously described [64] with the Ki67 cut-off at 14% for distinguishing between Luminal A and Luminal B tumors. In addition, cytokeratin-5 (CK5) and epidermal growth factor receptor (EGFR) IHC was applied for typing basal-like carcinomas, with 1% cut-off for positivity, as suggested [65].…”

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

“…Another subtype, referred to as the claudin-low subtype, was later described (15,16). Furthermore, a subpopulation of the luminal A subtype with a Ki-67 proliferation index of >14% was designated as the luminal B subtype (17) (18)(19)(20).…”