Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies

Matteo Lambertini, Marcello Ceppi, Francesco Cognetti, Giovanna Cavazzini, Michele De Laurentiis, Sabino De Placido, Andrea Michelotti, Giancarlo Bisagni, Antonio Durando, Enrichetta Valle, Tiziana Scotto, Andrea De Censi, Anna Turletti, Marco Benasso, Sandro Barni, Filippo Montemurro, Fabio Puglisi, Alessia Levaggi, Sara Giraudi, Claudia BighinPaolo Bruzzi, Lucia Del Mastro, MIG and GIM study groups

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea.

PATIENTS AND METHODS: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates.

RESULTS: A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54-0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54-1.12) and 0.65 (95% CI, 0.40-1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80-1.25; p = 0.989).

CONCLUSION: Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalEuropean Journal of Cancer
Volume71
DOIs
Publication statusPublished - Jan 2017

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Adjuvant Chemotherapy
Breast Neoplasms
Amenorrhea
Drug Therapy
Confidence Intervals
Logistic Models
Odds Ratio
Epirubicin
Survival
Therapeutics
Paclitaxel
Proportional Hazards Models
Cyclophosphamide
Meta-Analysis
Randomized Controlled Trials
Hormones
Neoplasms

Keywords

  • Adult
  • Amenorrhea
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Chemotherapy, Adjuvant
  • Cyclophosphamide
  • Dose-Response Relationship, Drug
  • Epirubicin
  • Female
  • Fluorouracil
  • Humans
  • Middle Aged
  • Premenopause
  • Survival Analysis
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

Cite this

Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients : A pooled analysis of the MIG1 and GIM2 phase III studies. / Lambertini, Matteo; Ceppi, Marcello; Cognetti, Francesco; Cavazzini, Giovanna; De Laurentiis, Michele; De Placido, Sabino; Michelotti, Andrea; Bisagni, Giancarlo; Durando, Antonio; Valle, Enrichetta; Scotto, Tiziana; De Censi, Andrea; Turletti, Anna; Benasso, Marco; Barni, Sandro; Montemurro, Filippo; Puglisi, Fabio; Levaggi, Alessia; Giraudi, Sara; Bighin, Claudia; Bruzzi, Paolo; Del Mastro, Lucia; MIG and GIM study groups.

In: European Journal of Cancer, Vol. 71, 01.2017, p. 34-42.

Research output: Contribution to journalArticle

Lambertini, M, Ceppi, M, Cognetti, F, Cavazzini, G, De Laurentiis, M, De Placido, S, Michelotti, A, Bisagni, G, Durando, A, Valle, E, Scotto, T, De Censi, A, Turletti, A, Benasso, M, Barni, S, Montemurro, F, Puglisi, F, Levaggi, A, Giraudi, S, Bighin, C, Bruzzi, P, Del Mastro, L & MIG and GIM study groups 2017, 'Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies', European Journal of Cancer, vol. 71, pp. 34-42. https://doi.org/10.1016/j.ejca.2016.10.030
Lambertini, Matteo ; Ceppi, Marcello ; Cognetti, Francesco ; Cavazzini, Giovanna ; De Laurentiis, Michele ; De Placido, Sabino ; Michelotti, Andrea ; Bisagni, Giancarlo ; Durando, Antonio ; Valle, Enrichetta ; Scotto, Tiziana ; De Censi, Andrea ; Turletti, Anna ; Benasso, Marco ; Barni, Sandro ; Montemurro, Filippo ; Puglisi, Fabio ; Levaggi, Alessia ; Giraudi, Sara ; Bighin, Claudia ; Bruzzi, Paolo ; Del Mastro, Lucia ; MIG and GIM study groups. / Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients : A pooled analysis of the MIG1 and GIM2 phase III studies. In: European Journal of Cancer. 2017 ; Vol. 71. pp. 34-42.
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abstract = "BACKGROUND: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea.PATIENTS AND METHODS: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates.RESULTS: A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95{\%} confidence intervals [CI], 0.54-0.95; p = 0.021). The pooled HRs were 0.78 (95{\%} CI, 0.54-1.12) and 0.65 (95{\%} CI, 0.40-1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95{\%} CI, 0.80-1.25; p = 0.989).CONCLUSION: Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.",
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author = "Matteo Lambertini and Marcello Ceppi and Francesco Cognetti and Giovanna Cavazzini and {De Laurentiis}, Michele and {De Placido}, Sabino and Andrea Michelotti and Giancarlo Bisagni and Antonio Durando and Enrichetta Valle and Tiziana Scotto and {De Censi}, Andrea and Anna Turletti and Marco Benasso and Sandro Barni and Filippo Montemurro and Fabio Puglisi and Alessia Levaggi and Sara Giraudi and Claudia Bighin and Paolo Bruzzi and {Del Mastro}, Lucia and {MIG and GIM study groups}",
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year = "2017",
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doi = "10.1016/j.ejca.2016.10.030",
language = "English",
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TY - JOUR

T1 - Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients

T2 - A pooled analysis of the MIG1 and GIM2 phase III studies

AU - Lambertini, Matteo

AU - Ceppi, Marcello

AU - Cognetti, Francesco

AU - Cavazzini, Giovanna

AU - De Laurentiis, Michele

AU - De Placido, Sabino

AU - Michelotti, Andrea

AU - Bisagni, Giancarlo

AU - Durando, Antonio

AU - Valle, Enrichetta

AU - Scotto, Tiziana

AU - De Censi, Andrea

AU - Turletti, Anna

AU - Benasso, Marco

AU - Barni, Sandro

AU - Montemurro, Filippo

AU - Puglisi, Fabio

AU - Levaggi, Alessia

AU - Giraudi, Sara

AU - Bighin, Claudia

AU - Bruzzi, Paolo

AU - Del Mastro, Lucia

AU - MIG and GIM study groups

N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.

PY - 2017/1

Y1 - 2017/1

N2 - BACKGROUND: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea.PATIENTS AND METHODS: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates.RESULTS: A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54-0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54-1.12) and 0.65 (95% CI, 0.40-1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80-1.25; p = 0.989).CONCLUSION: Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.

AB - BACKGROUND: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea.PATIENTS AND METHODS: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates.RESULTS: A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54-0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54-1.12) and 0.65 (95% CI, 0.40-1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80-1.25; p = 0.989).CONCLUSION: Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.

KW - Adult

KW - Amenorrhea

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Breast Neoplasms

KW - Chemotherapy, Adjuvant

KW - Cyclophosphamide

KW - Dose-Response Relationship, Drug

KW - Epirubicin

KW - Female

KW - Fluorouracil

KW - Humans

KW - Middle Aged

KW - Premenopause

KW - Survival Analysis

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejca.2016.10.030

DO - 10.1016/j.ejca.2016.10.030

M3 - Article

C2 - 27951450

VL - 71

SP - 34

EP - 42

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -