title: Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX.
abstract: OBJECTIVE
  To retrospectively evaluate the pattern of recurrence and outcome of node-negative breast cancer (BC) according to major subtypes.
  
  
  METHODS
  In all, 1,951 patients with node-negative, early-stage BC randomly assigned in International Breast Cancer Study Group Trials VIII and IX with centrally reviewed pathology data were included. BC subtypes were defined as triple negative (TN; n = 310), human epidermal growth factor receptor 2 (HER2) positive (n = 369), and hormone receptor positive with high (luminal B-like [LB-like]; n = 763) or low (luminal A-like [LA-like]; n = 509) proliferative activity by Ki-67 labeling index. BC-free interval (BCFI) events were invasive BC recurrence in local, contralateral breast, nodal, bone, or visceral sites. Time to first site-specific recurrence was evaluated by using cumulative incidence and competing risks regression analysis.
  
  
  RESULTS
  Median follow-up was 12.5 years. The 10-year BCFI was higher for patients with LA-like (86%) BC compared with LB-like (76%), HER2 (73%), and TN (71%; P < .001) BC. TN and HER2 cohorts had higher hazard of BCFI event in the first 4 years after diagnosis (pre-trastuzumab). LB-like cohorts had a continuously higher hazard of BCFI event over time compared with LA-like cohorts. Ten-year overall survival was higher for LA-like (89%) compared with LB-like (83%), HER2 (77%), and TN (75%; P < .001) BC. LB-like subtypes had higher rates of bone as first recurrence site than other subtypes (P = .005). Visceral recurrence as first site was lower for the LA-like subgroup, with similar incidence among the other subgroups when treated with chemotherapy (P = .003).
  
  
  CONCLUSIONS
  BC subtypes have different distant recurrence patterns over time. Defining different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of clinical studies.
authors.affiliation: Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Otto
authors.initials: O
authors.lastname: Metzger-Filho
authors.forename: Zhuoxin
authors.initials: Z
authors.lastname: Sun
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Diana
authors.initials: D
authors.lastname: Crivellari
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Snyder
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
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