title: Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil.
abstract: OBJECTIVE
  To compare sequential methotrexate (M) and fluorouracil (F) (M-->F) with surgery (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-13) and cyclophosphamide (C), M, and F with M-->F (NSABP B-19), in patients with estrogen receptor (ER)-negative tumors and negative axillary nodes.
  
  
  METHODS
  A total of 760 patients were randomized to B-13; 1,095 patients with the same eligibility requirements were randomized to B-19. Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were determined using life-table estimates.
  
  
  RESULTS
  A significant benefit in overall DFS (74% v 59%; P < .001) was demonstrated at 8 years in all B-13 patients who received M-->F (69% v 56% [P = .006] in those <or= 49 years of age, and 81% v 63% [P = .002] in those >or= 50 years). A survival advantage was evident in older patients (89% v 80%; P = .03). In B-19, through 5 years, an overall DFS advantage (82% v 73%; P < .001) and a borderline survival advantage (88% v 85%; P = .06) were evident with CMF. The DFS (84% v 72%; P < .001) and survival (89% v 84%; P = .04) benefits from CMF were greater in women aged <or= 49 years. M-->F or CMF after lumpectomy and breast irradiation resulted in a low probability of ipsilateral breast tumor recurrence (IBTR). In B-13, the frequency of IBTR was 2.6% following M-->F versus 13.4% in women treated by lumpectomy; it was 0.6% following CMF in B-19. Toxicity >or= grade 3 was more frequent among CMF patients in B-19. The age-related difference in CMF benefit was not related to amount of drug received.
  
  
  CONCLUSIONS
  M-->F and CMF are effective for node-negative patients with ER-negative tumors. The incidence of local-regional or distant metastases and IBTR decreased after either therapy. The benefit from either therapy was evident in all patients, but the CMF advantage was greater in those <or= 49 years. Because it is less toxic, M-->F may be used in patients with medical problems that would preclude CMF administration.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project Scientific Director's Office, Pittsburgh, PA 15261, USA. nsabpbft@pitt.edu
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: J
authors.initials: J
authors.lastname: Dignam
authors.forename: E P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: J P
authors.initials: JP
authors.lastname: Costantino
authors.forename: D L
authors.initials: DL
authors.lastname: Wickerham
authors.forename: C
authors.initials: C
authors.lastname: Redmond
authors.forename: N
authors.initials: N
authors.lastname: Wolmark
authors.forename: N V
authors.initials: NV
authors.lastname: Dimitrov
authors.forename: D M
authors.initials: DM
authors.lastname: Bowman
authors.forename: A G
authors.initials: AG
authors.lastname: Glass
authors.forename: J N
authors.initials: JN
authors.lastname: Atkins
authors.forename: N
authors.initials: N
authors.lastname: Abramson
authors.forename: C M
authors.initials: CM
authors.lastname: Sutherland
authors.forename: B S
authors.initials: BS
authors.lastname: Aron
authors.forename: R G
authors.initials: RG
authors.lastname: Margolese
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011960:Receptors, Estrogen / Q000032:analysis*; D015996:Survival Rate
chemical_list: D011960:Receptors, Estrogen; D003520:Cyclophosphamide; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate