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

Research output: Contribution to journalArticle

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
Publication statusPublished - Jan 1 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/chemically induced, Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use, Breast Neoplasms/*drug therapy, Chemotherapy, Adjuvant, Cyclophosphamide/adverse effects/therapeutic use, Dose-Response Relationship, Drug, Epirubicin/adverse effects/therapeutic use, Female, Fluorouracil/adverse effects/therapeutic use, Humans, Middle Aged, Premenopause, Survival Analysis, *Breast cancer, *Dose-dense chemotherapy, *Premenopausal patients, *Treatment-induced amenorrhoea

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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.

In: European Journal of Cancer, Vol. 71, 01.01.2017, 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 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.
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. / 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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title = "Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies.",
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.",
keywords = "Adult, Amenorrhea/chemically induced, Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use, Breast Neoplasms/*drug therapy, Chemotherapy, Adjuvant, Cyclophosphamide/adverse effects/therapeutic use, Dose-Response Relationship, Drug, Epirubicin/adverse effects/therapeutic use, Female, Fluorouracil/adverse effects/therapeutic use, Humans, Middle Aged, Premenopause, Survival Analysis, *Breast cancer, *Dose-dense chemotherapy, *Premenopausal patients, *Treatment-induced amenorrhoea",
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",
year = "2017",
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volume = "71",
pages = "34--42",
journal = "European Journal of Cancer",
issn = "0959-8049",
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TY - JOUR

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

PY - 2017/1/1

Y1 - 2017/1/1

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, Amenorrhea/chemically induced, Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use, Breast Neoplasms/drug therapy, Chemotherapy, Adjuvant, Cyclophosphamide/adverse effects/therapeutic use, Dose-Response Relationship, Drug

M3 - Article

VL - 71

SP - 34

EP - 42

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -