title: Factors associated with local-regional recurrence after a negative sentinel node dissection: results of the ACOSOG Z0010 trial.
abstract: OBJECTIVE
  To determine factors important in local-regional recurrence (LRR) in patients with negative sentinel lymph nodes (SLNs) by hematoxylin and eosin (H&E) staining.
  
  
  BACKGROUND
  Z0010 was a prospective multicenter trial initiated in 1999 by the American College of Surgeons Oncology Group to evaluate occult disease in SLNs and bone marrow of early-stage breast cancer patients. Participants included women with biopsy-proven T1-2 breast cancer with clinically negative nodes, planned for lumpectomy and whole breast irradiation.
  
  
  METHODS
  Women with clinical T1-2,N0,M0 disease underwent lumpectomy and SLN dissection. There was no axillary-specific treatment for H&E-negative SLNs, and clinicians were blinded to immunohistochemistry results. Systemic therapy was based on primary tumor factors. Univariable and multivariable analyses were performed to determine clinicopathologic factors associated with LRR.
  
  
  RESULTS
  Of 5119 patients, 3904 (76.3%) had H&E-negative SLNs. Median age was 57 years (range 23-95). At median follow-up of 8.4 years, there were 127 local, 20 regional, and 134 distant recurrences. Factors associated with local-regional recurrence were hormone receptor-negative disease (P = 0.0004) and younger age (P = 0.047). In competing risk-regression models, hormone receptor-positive disease and use of chemotherapy were associated with reduction in local-regional recurrence. When local recurrence was included in the model as a time-dependent variable, older age, T2 disease, high tumor grade, and local recurrence were associated with reduced overall survival.
  
  
  CONCLUSIONS
  Local-regional recurrences are rare in early-stage breast cancer patients with H&E-negative SLNs. Younger age and hormone receptor-negative disease are associated with higher event rates, and local recurrence is associated with reduced overall survival.
authors.affiliation: Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA. khunt@mdanderson.org
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Linda M
authors.initials: LM
authors.lastname: McCall
authors.forename: Judy C
authors.initials: JC
authors.lastname: Boughey
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
authors.forename: Charles E
authors.initials: CE
authors.lastname: Cox
authors.forename: Pat W
authors.initials: PW
authors.lastname: Whitworth
authors.forename: Peter D
authors.initials: PD
authors.lastname: Beitsch
authors.forename: A Marilyn
authors.initials: AM
authors.lastname: Leitch
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Monica A
authors.initials: MA
authors.lastname: Morrow
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D021701:Sentinel Lymph Node Biopsy; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone