title: Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; Department of Medicine, BrEAST Data Centre, Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: matteo.lambertini85@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: Epidemiology Unit, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: marcello.ceppi@hsanmartino.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ceppi
authors.affiliation: Department of Medical Oncology, Istituto Regina Elena per lo Studio e la Cura dei Tumori, Roma, Italy. Electronic address: cognetti@ifo.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.affiliation: Medical Oncology, Azienda Ospedaliera Carlo Poma, Mantova, Italy. Electronic address: mariagiovanna.cavazzini@aopoma.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cavazzini
authors.affiliation: Medical Oncology, Istituto Nazionale Tumori-IRCCS Fondazione Pascale, Napoli, Italy. Electronic address: delauren@unina.it.
authors.forename: Michele
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Federico II, Napoli, Italy. Electronic address: deplacid@unina.it.
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.affiliation: UO Oncologia Medica I, Ospedale S. Chiara, Dipartimento di oncologia, dei trapianti e delle nuove tecnologie, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. Electronic address: a.michelotti@ao-pisa.toscana.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Michelotti
authors.affiliation: Medical Oncology, IRCCS Arcispedale S. Maria Nuova, Reggio Emilia, Italy. Electronic address: bisagni.giancarlo@asmn.re.it.
authors.forename: Giancarlo
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authors.lastname: Bisagni
authors.affiliation: Breast Unit, Azienda Ospedaliera Universitaria Città della Salute e delle Scienze, Torino, Italy. Electronic address: andurando63@gmail.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Durando
authors.affiliation: Medical Oncology, ASL8-Ospedale Oncologico A. Businco, Cagliari, Italy. Electronic address: enrichettavalle@asl8cagliari.it.
authors.forename: Enrichetta
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authors.lastname: Valle
authors.affiliation: U.O. Oncologia Medica, Ospedale Civile, Sassari, Italy. Electronic address: scotto.tiziana@libero.it.
authors.forename: Tiziana
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authors.lastname: Scotto
authors.affiliation: S.C. Oncologia Medica, Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy. Electronic address: andrea.decensi@galliera.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Censi
authors.affiliation: Medical Oncology, ASLTO1, Torino, Italy. Electronic address: annaturletti@virgilio.it.
authors.forename: Anna
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authors.lastname: Turletti
authors.affiliation: Medical Oncology, Ospedale San Paolo, Savona, Italy. Electronic address: m.benasso@asl2.liguria.it.
authors.forename: Marco
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authors.lastname: Benasso
authors.affiliation: Medical Oncology, Azienda Ospedaliera, Caravaggio, Treviglio, Bergamo, Italy. Electronic address: sandro.barni@ospedale.treviglio.bg.it.
authors.forename: Sandro
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authors.lastname: Barni
authors.affiliation: Investigative Clinical Oncology, Fondazione del Piemonte per l'Oncologia/Candiolo Cancer Center (IRCCS), Candiolo, Torino, Italy. Electronic address: filippo.montemurro@ircc.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
authors.affiliation: Department of Oncology, Azienda Ospedaliera di Udine, Udine, Italy. Electronic address: fabio.puglisi@uniud.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: alessia.levaggi@hsanmartino.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Levaggi
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: sara.giraudi@hsanmartino.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Giraudi
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: claudia.bighin@hsanmartino.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bighin
authors.affiliation: Epidemiology Unit, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: paolo.bruzzi@hsanmartino.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: lucia.delmastro@hsanmartino.it.
authors.forename: Lucia
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authors.lastname: Del Mastro
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D016019:Survival Analysis
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil
keywords: Breast cancer; Dose-dense chemotherapy; Premenopausal patients; Treatment-induced amenorrhoea