Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: A hellenic cooperative oncology group observational study (HE 10/10) with concurrent investigation of significance of tumor infiltrating lymphocytes
Foteinos-Ioannis Dimitrakopoulos,
Anna Goussia,
Georgia-Angeliki Koliou,
Katerina Dadouli,
Anna Batistatou,
Helen P. Kourea,
Mattheos Bobos,
Petroula Arapantoni-Dadioti,
Olympia Tzaida,
Triantafyllia Koletsa,
Sofia Chrisafi,
Maria Sotiropoulou,
Alexandra Papoudou-Bai,
Irene Nicolaou,
Antonia Charchanti,
Davide Mauri,
Gerasimos Aravantinos,
Ioannis Binas,
Eleni Res,
Amanda Psyrri,
Dimitrios Pectasides,
Dimitrios Bafaloukos,
Anna Koumarianou,
Iliada Bompolaki,
Georgios Rigakos,
Charisios Karanikiotis,
Angelos Koutras,
Flora Zagouri,
Helen Gogas,
George Fountzilas
Affiliations
Foteinos-Ioannis Dimitrakopoulos
Division of Oncology, University Hospital of Patras ''Panagia the Help'', University of Patras, Patras, Greece; Molecular Oncology Laboratory, Department of Medicine, University of Patras, Patras, Greece; Corresponding author. Division of Oncology, University Hospital, University of Patras, Patras, Greece.
Anna Goussia
Department of Pathology, Ioannina University Hospital, Ioannina, Greece; Department of Pathology, German Oncology Center, Limassol, Cyprus
Georgia-Angeliki Koliou
Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece
Katerina Dadouli
Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, Larissa, Greece
Anna Batistatou
Department of Pathology, Ioannina University Hospital, Ioannina, Greece
Helen P. Kourea
Department of Pathology, University Hospital of Patras, Rion, Greece
Mattheos Bobos
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Biomedical Sciences, School of Health Sciences, International Hellenic University, Thessaloniki, Greece
Petroula Arapantoni-Dadioti
Department of Pathology, Henry Dunant Hospital, Athens, Greece
Olympia Tzaida
Department of Pathology, Metaxas Cancer Hospital, Piraeus, Greece
Triantafyllia Koletsa
Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
Sofia Chrisafi
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece
Maria Sotiropoulou
Department of Pathology, Alexandra Hospital, Athens, Greece
Alexandra Papoudou-Bai
Department of Pathology, Ioannina University Hospital, Ioannina, Greece
Irene Nicolaou
Department of Histopathology, Agii Anargiri Hospital, Athens, Greece
Antonia Charchanti
Department of Anatomy-Histology-Embryology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
Davide Mauri
Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece
Gerasimos Aravantinos
Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
Ioannis Binas
Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece
Eleni Res
Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
Amanda Psyrri
Section of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, Faculty of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
Dimitrios Pectasides
Oncology Section, Second Department of Internal Medicine, Hippokratio Hospital, Athens, Greece
Dimitrios Bafaloukos
First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece
Anna Koumarianou
Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Greece
Iliada Bompolaki
Oncology Department, General Hospital of Chania, Crete, Greece
Georgios Rigakos
Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece
Charisios Karanikiotis
Department of Medical Oncology, 424 Army General Hospital, Thessaloniki, Greece
Angelos Koutras
Division of Oncology, University Hospital of Patras ''Panagia the Help'', University of Patras, Patras, Greece
Flora Zagouri
Department of Clinical Therapeutics, Alexandra Hospital, National Andistrian U Kapodniversity of Athens School of Medicine, Athens, Greece
Helen Gogas
First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
George Fountzilas
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Medical Oncology, German Oncology Center, Limassol, Cyprus
Background: Dose-dense sequential (dds) chemotherapy has changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a currently widely used chemotherapeutic regimen. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. Patients and methods: Totally, 1054 patients were prospectively enrolled in the current study with 1024 patients being eligible, while adequate tissue was available for 596 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. Results: Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. Importantly, the 10-year DFS and OS rates were 78.4% (95% CI 75.0–81.5) and 81.7% (95% CI 79.0–84.1), respectively. Interestingly, higher CD8+ T cells as well as TILs in the tumor microenvironment were associated with an improved long-term survival outcome. Conclusions: In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of TILs and infiltrating CD8+ lymphocytes in BC patients with early-stage disease.
