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

PLoS One

Meletios A. Dimopoulos¹  George Fountzilas²  Vassiliki Kotoula³  Triantafyllia Koletsa³  Vassiliki Malamou-Mitsi⁴  Anna Batistatou⁴  Helen Trihia⁵  Maria Sotiropoulou⁶  Savvas Papadopoulos⁷  Angelos Koutras⁸  Dimitrios Bafaloukos⁹  Helen Gogas^1,10  Spyros Miliaras^1,11  Urania Dafni^1,12  Sofia Chrisafi^1,13  Despina Televantou^1,13  Mattheos Bobos^1,13  Dimitrios Pectasides^1,14  Dimosthenis V. Skarlos^1,15  Konstantine T. Kalogeras^1,16  Theodoros Filippidis^1,17 

[1] Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine, Athens, Greece;Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Pathology, Ioannina University Hospital, Ioannina, Greece;Department of Pathology, Metaxas Cancer Hospital, Piraeus, Greece;Department of Pathology, “Alexandra” Hospital, Athens, Greece;Department of Pathology, “Hygeia” Hospital, Athens, Greece;Division of Oncology, Department of Medicine, University Hospital, University of Patras School of Medicine, Patras, Greece;First Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece;First Department of Medicine, “Laiko” General Hospital, University of Athens School of Medicine, Athens, Greece;First Department of Surgery, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Laboratory of Biostatistics, University of Athens School of Nursing, Athens, Greece;Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Second Department of Internal Medicine, Oncology Section, “Hippokration” Hospital, Athens, Greece;Second Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece;Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece;“Micromedica” Histopathology Laboratory, Athens, Greece

关键词: Breast cancer;    Cancer treatment;    Adjuvant chemotherapy;    Cancer chemotherapy;    Immunologic adjuvants;    Polymers;    Immunohistochemistry techniques;    Prognosis;   

DOI  :  10.1371/journal.pone.0037946

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background The 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 Methods Formalin-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). Results After 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. Conclusions Triple-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.

【 授权许可】

CC BY