title: Measures of outcome in metastatic breast cancer: insights from a real-world scenario.
abstract: No gold standard treatment exists for metastatic breast cancer (MBC). Clinical decision making is based on knowledge of prognostic and predictive factors that are extrapolated from clinical trials and, sometimes, are not reliably transferable to a real-world scenario. Moreover, misalignment between endpoints used in drug development and measures of outcome in clinical practice has been noted. The roles of overall survival (OS) and progression-free survival (PFS) as primary endpoints in the context of clinical trials are the subjects of lively debate. Information about these parameters in routine clinical practice is potentially useful to design new studies and/or to interpret the results of clinical research. This study analyzed the impact of patient and tumor characteristics on the major measures of outcome across different lines of treatment in a cohort of 472 patients treated for MBC. OS, PFS, and postprogression survival (PPS) were analyzed. The study showed how biological and clinical characteristics may have different prognostic value across different lines of therapy for MBC. After first-line treatment, the median PPS of luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2)-positive groups was longer than 12 months. The choice of OS as a primary endpoint for clinical trials could not be appropriate with these subtypes. In contrast, OS could be an appropriate endpoint when PPS is expected to be low (e.g., triple-negative subtype after the first line; other subtypes after the third line). The potential implications of these findings are clinical and methodological.
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bonotto
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gerratana
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Poletto
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Driol
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Giangreco
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Russo
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Minisini
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Andreetta
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Mansutti
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Federica E
authors.initials: FE
authors.lastname: Pisa
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: Department of Oncology and Institute of Hygiene and Clinical Epidemiology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; General Hospital, Gorizia, Italy fabio.puglisi@uniud.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast neoplasms; Outcome measure; Surrogate endpoint; Survival analysis