title: Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: a retrospective cohort study.
abstract: BACKGROUND
  The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration.
  
  
  METHODS
  A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics.
  
  
  RESULTS
  At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for < 7.2 months, 7.2 to 14 months, and > 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR]positive vs. negative = 2.39 [95% confidence interval (CI), 1.08-5.31]; P = .032); and a lower likelihood of having received adjuvant trastuzumab (ORadjuvant trastuzumab vs. no adjuvant trastuzumab = 0.30 [95% CI, 0.10-0.96]; P = .043]. C-statistics varied between 0.634 and 0.699.
  
  
  CONCLUSIONS
  Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Breast Oncology Center, Boston, MA 02215, USA.
authors.forename: Ines
authors.initials: I
authors.lastname: Vaz-Luis
authors.forename: Davinia
authors.initials: D
authors.lastname: Seah
authors.forename: Erin M
authors.initials: EM
authors.lastname: Olson
authors.forename: Nikhil
authors.initials: N
authors.lastname: Wagle
authors.forename: Otto
authors.initials: O
authors.lastname: Metzger-Filho
authors.forename: Jessica
authors.initials: J
authors.lastname: Sohl
authors.forename: Georgia
authors.initials: G
authors.lastname: Litsas
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D010818:Practice Patterns, Physicians'; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human
keywords: HER2-positive; Outcomes; Treatment Duration