title: Site of primary tumor has a prognostic role in operable breast cancer: the international breast cancer study group experience.
abstract: OBJECTIVE
  Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease.
  
  
  METHODS
  Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years.
  
  
  RESULTS
  A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS).
  
  
  CONCLUSIONS
  Tumor site has a significant prognostic utility, especially for axillary lymph node-negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. marco.colleoni@ieo.it
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: David
authors.initials: D
authors.lastname: Zahrieh
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Stig B
authors.initials: SB
authors.lastname: Holmberg
authors.forename: Jan E
authors.initials: JE
authors.lastname: Mattsson
authors.forename: Carl-Magnus
authors.initials: CM
authors.lastname: Rudenstam
authors.forename: Jurij
authors.initials: J
authors.lastname: Lindtner
authors.forename: Darja
authors.initials: D
authors.lastname: Erzen
authors.forename: Raymond
authors.initials: R
authors.lastname: Snyder
authors.forename: John
authors.initials: J
authors.lastname: Collins
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fey
authors.forename: Beat
authors.initials: B
authors.lastname: Thürlimann
authors.forename: Diana
authors.initials: D
authors.lastname: Crivellari
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murray
authors.forename: Caesar
authors.initials: C
authors.lastname: Mendiola
authors.forename: Olivia
authors.initials: O
authors.lastname: Pagani
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Karen
authors.initials: K
authors.lastname: Price
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate