title: What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study.
abstract: BACKGROUND
  Despite the extensive clinical experience, it is still under debate to what extent patients with metastatic breast cancer (MBC) benefit from multiple lines of chemotherapy beyond standard first or second line treatment. Selection of patients with MBC who will benefit from treatment is crucial to improve outcome and reduce unnecessary toxicity. In this retrospective study, systemic treatment outcome for patients with metastatic MBC is being evaluated. We evaluated to what extent the clinical benefit of prior chemotherapy can predict the success of a subsequent treatment line.
  
  
  METHODS
  Ninety-one patients treated with chemotherapy for MBC between January 2005 and January 2009 were included in this study. Clinical characteristics of patients, choices of chemotherapy and response at first evaluation of every treatment line was evaluated based on radiologic and clinical data.
  
  
  RESULTS
  Patients received multiple systemic cytotoxic and biological (combination) therapies. 30% of these patients received more than five consecutive systemic (combination) treatments. First line chemotherapy was mostly anthracycline-based, followed by taxanes, capecitabine and vinorelbine. The response rate (RR, complete response plus partial response according to RECIST 1.1) decreased from 20% (95% CI 11-28%) upon first line of treatment to 0% upon the fourth line. The clinical benefit rate (combining RR and stable disease) decreased from 85% (95% CI 78-93%) in the first to 54% (95% CI 26-67) upon the fourth line. 24% of the patients with clinical benefit at first evaluation did not receive a subsequent line of treatment when progressive disease occurred, while sixty-one percent of the patients with progressive disease at first evaluation of a treatment did not receive a subsequent line of chemotherapy. When applied, the efficacy of a subsequent line of treatment was similar for patients independent of previous treatment benefit.
  
  
  CONCLUSIONS
  The clinical benefit at first evaluation from systemic treatment in MBC does not predict for subsequent treatment benefit in this retrospective analysis. The fact that 61% of patients did not receive subsequent treatment after previous treatment failure suggests that either clinical judgement is of critical value in selection of patients to prevent them from unnecessary toxicity or, alternatively indicates that based on the assumption that prior treatment failure predicts for lack of benefit undertreatment of patients occurs. Therefore, a more adequate clinical judgement tool or predictive biomarkers for response are urgently needed to improve treatment outcome.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: h.verheul@vumc.nl.
authors.forename: J L
authors.initials: JL
authors.lastname: Bakker
authors.affiliation: Department of Internal Medicine, Spaarne Ziekenhuis, Hoofddorp, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Wever
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: van Waesberghe
authors.affiliation: Department of Internal Medicine, Spaarne Ziekenhuis, Hoofddorp, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Beeker
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: I R
authors.initials: IR
authors.lastname: Konings
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: H M W
authors.initials: HM
authors.lastname: Verheul
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome
keywords: Beyond second line; Chemotherapy; Efficacy; Metastatic breast cancer; Retrospective analysis