Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial

on behalf of the GIM2 investigators

Research output: Contribution to journalArticle

Abstract

Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Adjuvant Chemotherapy
Breast Neoplasms
Drug Therapy
Disease-Free Survival
Survival
Trastuzumab
Epirubicin
Standard of Care
Paclitaxel
Fluorouracil
Cyclophosphamide

Keywords

  • adjuvant chemotherapy
  • breast cancer
  • dose-dense
  • HER2
  • trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{51037815f89a4f6bbcb0c7d0826277c3,
title = "Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial",
abstract = "Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95{\%} CI 0.52–1.89; OS: HR, 0.95; 95{\%} CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.",
keywords = "adjuvant chemotherapy, breast cancer, dose-dense, HER2, trastuzumab",
author = "{on behalf of the GIM2 investigators} and Matteo Lambertini and Francesca Poggio and Marco Bruzzone and Benedetta Conte and Claudia Bighin and {de Azambuja}, Evandro and Mario Giuliano and {De Laurentiis}, Michele and Francesco Cognetti and Alessandra Fabi and Giancarlo Bisagni and Antonio Durando and Anna Turletti and Ylenia Urracci and Ornella Garrone and Fabio Puglisi and Filippo Montemurro and Marcello Ceppi and {Del Mastro}, Lucia",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ijc.32789",
language = "English",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",

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T1 - Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab

T2 - Exploratory analysis of the GIM2 trial

AU - on behalf of the GIM2 investigators

AU - Lambertini, Matteo

AU - Poggio, Francesca

AU - Bruzzone, Marco

AU - Conte, Benedetta

AU - Bighin, Claudia

AU - de Azambuja, Evandro

AU - Giuliano, Mario

AU - De Laurentiis, Michele

AU - Cognetti, Francesco

AU - Fabi, Alessandra

AU - Bisagni, Giancarlo

AU - Durando, Antonio

AU - Turletti, Anna

AU - Urracci, Ylenia

AU - Garrone, Ornella

AU - Puglisi, Fabio

AU - Montemurro, Filippo

AU - Ceppi, Marcello

AU - Del Mastro, Lucia

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.

AB - Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.

KW - adjuvant chemotherapy

KW - breast cancer

KW - dose-dense

KW - HER2

KW - trastuzumab

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