title: Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines?
abstract: BACKGROUND
  Despite the availability of several therapeutic options for metastatic breast cancer (MBC), no robust predictive factors are available to help clinical decision making. Nevertheless, a decreasing benefit from first line to subsequent lines of treatment is commonly observed. The aim of this study was to assess the impact of benefit from first-line therapy on outcome with subsequent lines.
  
  
  METHODS
  We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) between 2004 and 2012. We evaluated progression-free survival (PFS) at first (PFS1), second, third, and fourth therapeutic lines, according to treatment (ET and/or CT) and tumor subtypes.
  
  
  RESULTS
  In the whole cohort, median overall survival was 34 months, and median PFS1 was 9 months. A 6-month benefit was shown by 289 patients (63.5%) at first line, 128 (40.5%) at second line, 76 (33.8%) at third line, and 34 (23.3%) at fourth line. Not having a 6-month benefit at PFS1 was associated with less chance of benefit at second line (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29-0.77, p = .0026) and at any line beyond first (OR: 0.39; 95% CI: 0.24-0.62, p < .0001). In the total series, after stratification for tumor subtypes, a strong predictive effect was observed among HER2-positive tumors (OR: 0.2; 95% CI: 0.05-0.73, p = .0152).
  
  
  CONCLUSIONS
  Our results suggest that the absence of at least a 6-month benefit in terms of PFS with first-line therapy predicts a reduced probability of benefit from subsequent therapeutic lines, especially in HER2-positive disease.
  
  
  CONCLUSIONS
  This study supports evidence showing that the absence of a 6-month benefit in terms of progression-free survival with first-line therapy predicts a lack of benefit from subsequent therapeutic lines in metastatic breast cancer. The random distribution of benefit experienced by a subset of the cohort further spurs an interest in identifying predictive factors capable of identifying the most appropriate therapeutic strategy.
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bonotto
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gerratana
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Iacono
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Alessandro Marco
authors.initials: AM
authors.lastname: Minisini
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Karim
authors.initials: K
authors.lastname: Rihawi
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: Department of Oncology, University Hospital of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy fabio.puglisi@uniud.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology
keywords: Breast neoplasms; Decision making; Overall survival; Treatment outcome