title: Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer.
abstract: BACKGROUND
  This retrospective study sought to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC).
  
  
  METHODS
  A total of 2448 patients with stage I through III TNBC who were diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. The Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases.
  
  
  RESULTS
  At a median follow-up of 39 months, 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% confidence interval [CI] = 2.9%-4.5%) and 5.4% (95% CI = 4.4%-6.5%), respectively. Among patients with stage I, II, and III disease, the 2-year cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P < .0001). The 5-year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients with stage I, II, and III disease, respectively (P < .0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (hazards ratio = 3.51; 95% CI = 1.85-6.67; P = .0001) compared to patients with stage I disease. Those with stage II disease had a nonsignificant increased risk of developing brain metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92-2.81; P = .10) compared with patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range, 5.7-9.4 months).
  
  
  CONCLUSIONS
  Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies.
authors.affiliation: Department of Medical Oncology, Dubai Hospital, United Arab Emirates. Shaheenah_d@yahoo.com
authors.forename: Shaheenah
authors.initials: S
authors.lastname: Dawood
authors.forename: Xiudong
authors.initials: X
authors.lastname: Lei
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Litton
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000453:epidemiology / Q000556:secondary*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human