title: Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy.
abstract: BACKGROUND
  We examined the prognostic value of biologic subtype on locoregional recurrence (LRR) after mastectomy in a cohort of low risk women who did not receive adjuvant radiation therapy.
  
  
  METHODS
  A total of 819 patients with invasive breast cancer underwent mastectomy from January 2000 through December 2005. No patient received preoperative chemotherapy. Estrogen receptor (ER) receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were used to construct the following 4 subtypes: i) ER+ or PR+ and HER2- (HR+/HER2-), ii) ER+ or PR+ and HER2+ (HR+/HER2+), iii) ER- and PR- and HER2+ (HR-/HER2+)and iv) ER- and PR- and HER2- (HR-/HER2-). LRR-free survival was estimated by the Kaplan-Meier method. Cox proportional hazard models were used to evaluate the association between time-to-event outcomes and patient prognostic factors.
  
  
  RESULTS
  At a median follow-up of 58 months, five-year cumulative incidence of LRR for the entire cohort was 2.5%. Subtype specific LRR rates were 1% for HR+/HER2-, 6.5% in HR+/HER2+, 2% for HR-/HER2+ and 10.9% for HR-/HER2- (P < 0.01). In HER-2+ patients (irrespective of ER/PR status), trastuzumab therapy was not associated with LRR-free survival. On multivariate analysis, one to three positive lymph nodes (HR 4.75 (confidence interval (CI) 1.75 to 12.88, P < 0.01), ≥ 4 positive lymph nodes (HR23.4 (CI 4.64 to 117.94, P < 0.01), HR+/HER2+ (HR 4.26 (CI 1.05 to 17.33), P = 0.04), and HR-/HER2- phenotype (HR 13.87 (CI 4.96 to 38.80), P < 0.01) were associated with shorter LRR-free survival whereas age > 50 at diagnosis (HR 0.31 (CI 0.12 to 0.80), P = 0.02) was associated with improved LRR-free survival. Among the HR-/HER2- subtypes, five-year LRR incidence was 23.4% in patients with positive lymph nodes compared to 7.8% for lymph node negative patients (P = 0.01), although this association did not reach significance when the analysis was limited to HR-/HER2- women with only one to three positive lymph nodes (15.6% versus 7.8%, P = 0.11).
  
  
  CONCLUSIONS
  Constructed subtype is a prognostic factor for LRR after mastectomy among low risk women not receiving adjuvant radiation therapy, although rates of LRR remain low across subtypes. Patients with node positive, HR-/HER2- type tumors were more likely to experience LRR following mastectomy alone. Prospective studies to further investigate the potential benefit of adjuvant radiation therapy in these women are warranted.
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Dominici
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
authors.forename: Xumei
authors.initials: X
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kuerer
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.forename: Abenaa
authors.initials: A
authors.lastname: Brewster
authors.forename: Gildy V
authors.initials: GV
authors.lastname: Babiera
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bedrosian
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008408:Mastectomy; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human