Pooled Analysis of Patients With Early-stage Breast Cancer Treated With Adjuvant Dose-dense Sequential Chemotherapy: a Hellenic Cooperative Oncology Group (HeCOG) Study.

NCT07521397 | Completed

• 1 other identifier: ΗE_10R/22
• Study Type: observational
• Target: 5,358
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to assess survival outcomes and treatment-related toxicity in patients with early-stage breast cancer receiving adjuvant therapies, using high-quality individual patient data pooled from seven clinical studies conducted by the Hellenic Cooperative Oncology Group (HeCOG), including 3 phase III trials and 4 observational studies. This study aims to assess long-term disease-free survival (DFS) and overall survival (OS), as well as the toxicity patterns associated with dose-dense sequential chemotherapy in intermediate or high-rsk patients.

Conditions

Breast Cancer; Early Stage Breast Cancer; Adjuvant Chemotherapy; Prognosis Breast Cancer; Overall Survival

Keywords

dose-dense sequential chemotherapy; breast cancer; prognostic biomarker

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival

  Disease-Free survival is defined as the time from diagnosis or surgery to the first documented recurrence of breast cancer (local, regional, or distant) or death from any cause. Patients without an event are censored at the last follow-up.

  From date of diagnosis or surgery to first documented recurrence or death.

Secondary Outcomes (3)

• Overall survival

  From date of diagnosis or surgery to death from any cause. Patients alive at last follow-up are censored at that date

• Treatment-related toxicity

  From the first dose of treatment until 5 years after the last dose

• Overall survival

  From the date of diagnosis to the date of death

Study Arms (1)

Early Breast Cancer Cohort

Patients with early-stage breast cancer included in pooled individual patient data from seven clinical studies conducted by the Hellenic Cooperative Oncology Group (HeCOG). Patients received adjuvant treatment.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes 5,378 patients with early-stage, surgically resected breast cancer of high or intermediate risk who participated in seven observational studies (three phase III trials and four observational studies) conducted by the Hellenic Cooperative Oncology Group (HeCOG). All patients received adjuvant dose-dense sequential chemotherapy (ddsc), and individual patient-level data were available for demographic, pathological, treatment, and outcome variables.

You may qualify if:

• Patients with early-stage, surgically resected breast cancer (high or intermediate risk), randomized to receive adjuvant or neoadjuvant dose-dense sequential chemotherapy.

You may not qualify if:

• Patients with metastatic or locally advanced breast cancer at initial diagnosis.
• Patients who did not receive dose-dense sequential chemotherapy.

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead

Study Sites (1)

Unknown Facility

Athens, 11526, Greece

Location

Related Publications (15)

• Breast Cancer. NCCN clinical practice guideline in Oncology.https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

  BACKGROUND

• Fountzilas G, Dafni U, Papadimitriou C, Timotheadou E, Gogas H, Eleftheraki AG, Xanthakis I, Christodoulou C, Koutras A, Papandreou CN, Papakostas P, Miliaras S, Markopoulos C, Dimitrakakis C, Korantzopoulos P, Karanikiotis C, Bafaloukos D, Kosmidis P, Samantas E, Varthalitis I, Pavlidis N, Pectasides D, Dimopoulos MA. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial. BMC Cancer. 2014 Jul 15;14:515. doi: 10.1186/1471-2407-14-515.

  PMID: 25026897 BACKGROUND

• Papadimitriou CA, Papakostas P, Timotheadou E, Aravantinos G, Bamias A, Fountzilas G. Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF and weekly paclitaxel in patients with resected high-risk breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Cancer Invest. 2008 Jun;26(5):491-8. doi: 10.1080/07357900701829785.

  PMID: 18568771 BACKGROUND

• Fountzilas G, Pectasides D, Christodoulou C, Timotheadou E, Economopoulos T, Papakostas P, Papadimitriou C, Gogas H, Efstratiou I, Skarlos D. Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF, and weekly docetaxel is feasible and safe in patients with operable breast cancer. Med Oncol. 2006;23(4):479-88. doi: 10.1385/MO:23:4:479.

  PMID: 17303906 BACKGROUND

• Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D, Christodoulou C, Markopoulos C, Briasoulis E, Papakostas P, Samantas E, Kosmidis P, Stathopoulos GP, Karanikiotis C, Pectasides D, Dimopoulos MA, Fountzilas G. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat. 2012 Apr;132(2):609-19. doi: 10.1007/s10549-011-1913-4. Epub 2011 Dec 21.

  PMID: 22187126 BACKGROUND

• Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D, Papadimitriou C, Markopoulos C, Polychronis A, Kalofonos HP, Siafaka V, Kosmidis P, Timotheadou E, Tsavdaridis D, Bafaloukos D, Papakostas P, Razis E, Makrantonakis P, Aravantinos G, Christodoulou C, Dimopoulos AM. Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 2005 Nov;16(11):1762-71. doi: 10.1093/annonc/mdi366. Epub 2005 Sep 7.

  PMID: 16148021 BACKGROUND

• Stewart LA, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, Tierney JF; PRISMA-IPD Development Group. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement. JAMA. 2015 Apr 28;313(16):1657-65. doi: 10.1001/jama.2015.3656.

  PMID: 25919529 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018 Jan;19(1):27-39. doi: 10.1016/S1470-2045(17)30777-5. Epub 2017 Dec 11.

  PMID: 29242041 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019 Apr 6;393(10179):1440-1452. doi: 10.1016/S0140-6736(18)33137-4. Epub 2019 Feb 8.

  PMID: 30739743 BACKGROUND

• Early Breast Cancer Trialists' Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol. 2021 Aug;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6.

  PMID: 34339645 BACKGROUND

• Paakkola NM, Karakatsanis A, Mauri D, Foukakis T, Valachis A. The prognostic and predictive impact of low estrogen receptor expression in early breast cancer: a systematic review and meta-analysis. ESMO Open. 2021 Dec;6(6):100289. doi: 10.1016/j.esmoop.2021.100289. Epub 2021 Oct 19.

  PMID: 34678571 BACKGROUND

• Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M, Hayes DF; EBCTCG. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017 Nov 9;377(19):1836-1846. doi: 10.1056/NEJMoa1701830.

  PMID: 29117498 BACKGROUND

• Berlin JA, Santanna J, Schmid CH, Szczech LA, Feldman HI; Anti-Lymphocyte Antibody Induction Therapy Study Group. Individual patient- versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head. Stat Med. 2002 Feb 15;21(3):371-87. doi: 10.1002/sim.1023.

  PMID: 11813224 BACKGROUND

• Kerr AJ, Dodwell D, McGale P, Holt F, Duane F, Mannu G, Darby SC, Taylor CW. Adjuvant and neoadjuvant breast cancer treatments: A systematic review of their effects on mortality. Cancer Treat Rev. 2022 Apr;105:102375. doi: 10.1016/j.ctrv.2022.102375. Epub 2022 Mar 4.

  PMID: 35367784 BACKGROUND

• Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, Zackrisson S, Senkus E; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2019 Aug 1;30(8):1194-1220. doi: 10.1093/annonc/mdz173. No abstract available.

  PMID: 31161190 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

FFPE, peripheral blood

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2026
• First Posted: April 9, 2026
• Study Start: December 15, 1996
• Primary Completion: July 15, 2022
• Study Completion: July 15, 2022
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)