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 4 cycles of (fluorouracil)epirubicin/cyclophosphamide followed by 4 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. This article is protected by copyright. All rights reserved.

Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: exploratory analysis of the GIM2 trial / Lambertini, Matteo; Poggio, Francesca; Bruzzone, Marco; Conte, Benedetta; Bighin, Claudia; de Azambuja, Evandro; Giuliano, Mario; De Laurentiis, Michele; Cognetti, Francesco; Fabi, Alessandra; Bisagni, Giancarlo; Durando, Antonio; Turletti, Anna; Urracci, Ylenia; Garrone, Ornella; Puglisi, Fabio; Montemurro, Filippo; Ceppi, Marcello; Del Mastro, Lucia. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - (2019). [10.1002/ijc.32789]

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

Giuliano, Mario;De Laurentiis, Michele;
2019

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 4 cycles of (fluorouracil)epirubicin/cyclophosphamide followed by 4 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. This article is protected by copyright. All rights reserved.
2019
Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: exploratory analysis of the GIM2 trial / Lambertini, Matteo; Poggio, Francesca; Bruzzone, Marco; Conte, Benedetta; Bighin, Claudia; de Azambuja, Evandro; Giuliano, Mario; De Laurentiis, Michele; Cognetti, Francesco; Fabi, Alessandra; Bisagni, Giancarlo; Durando, Antonio; Turletti, Anna; Urracci, Ylenia; Garrone, Ornella; Puglisi, Fabio; Montemurro, Filippo; Ceppi, Marcello; Del Mastro, Lucia. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - (2019). [10.1002/ijc.32789]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/777331
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact