title: Risk factors for regional nodal relapse in breast cancer patients with one to three positive axillary nodes.
abstract: OBJECTIVE
  In many centers, supraclavicular fossa radiotherapy (SCF RT) is not routinely offered to breast cancer patients with one to three positive lymph nodes. We aimed to identify a subgroup of these patients who are at high risk of supra or infraclavicular fossa relapse (SCFR) such that they can be offered SCFRT at the time of diagnosis to improve long term locoregional control.
  
  
  METHODS
  We performed a retrospective analysis of the pathological features of 1,065 cases of invasive breast cancer with one to three positive axillary lymph nodes. Patients underwent radical breast conserving surgery or mastectomy. A total of 45% of patients received adjuvant chest wall/breast RT. No patients received adjuvant SCFRT. The primary outcome was SCFR. Secondary outcomes were chest wall/breast recurrence, distant metastasis, all death, and breast-cancer specific death. Kaplan-Meier estimates were used to calculate actuarial event rates and survival functions compared using log-rank tests. Multivariate analyses (MVA) of factors associated with outcome were conducted using Cox proportional hazards models.
  
  
  RESULTS
  Median follow-up was 9.7 years. SCFR rate was 9.2%. Median time from primary diagnosis to SCFR was 3.4 years (range, 0.7-14.4 years). SCFR was associated with significantly lower 10-year survival (18% vs. 65%; p < 0.001). Higher grade and number of positive lymph nodes were the most significant predictors of SCFR on MVA (p < 0.001). 10 year SCFR rates were less than 1% in all patients with Grade 1 cancers compared with 30% in those having Grade 3 cancers with three positive lymph nodes. Additional factors associated with SCFR on univariate analysis but not on MVA included larger nodal deposits (p = 0.002) and proportion of positive nodes (p = 0.003).
  
  
  CONCLUSIONS
  Breast cancer patients with one to three positive lymph nodes have a heterogenous risk of SCFR. Patients with two to three positive axillary nodes and/or high-grade disease may warrant consideration of SCFRT.
authors.affiliation: Guy's, King's, St Thomas' Cancer Centre, Guy's Hospital, London, UK. lucy.yates@gstt.nhs.uk
authors.forename: Lucy
authors.initials: L
authors.lastname: Yates
authors.forename: Anna
authors.initials: A
authors.lastname: Kirby
authors.forename: Siobhan
authors.initials: S
authors.lastname: Crichton
authors.forename: Cheryl
authors.initials: C
authors.lastname: Gillett
authors.forename: Paul
authors.initials: P
authors.lastname: Cane
authors.forename: Ian
authors.initials: I
authors.lastname: Fentiman
authors.forename: Elinor
authors.initials: E
authors.lastname: Sawyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D015182:Lymphatic Irradiation; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D018714:Radiotherapy, Adjuvant / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult