title: High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.
abstract: OBJECTIVE
  To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer.
  
  
  METHODS
  We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation.
  
  
  RESULTS
  Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors.
  
  
  CONCLUSIONS
  Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. agonzalez@mdanderson.org
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Litton
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Broglio
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Ronjay
authors.initials: R
authors.lastname: Rakkhit
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Florentia
authors.initials: F
authors.lastname: Peintinger
authors.forename: Emer O
authors.initials: EO
authors.lastname: Hanrahan
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Merih
authors.initials: M
authors.lastname: Guray
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Francesco
authors.initials: F
authors.lastname: Feoli
authors.forename: Heidi
authors.initials: H
authors.lastname: Stranzl
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Richard
authors.initials: R
authors.lastname: Theriault
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart-Gebhart
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ravdin
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis / Q000378:metabolism; D012307:Risk Factors
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone