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.

👉Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG.

PURPOSE: 

• To compare sequential methotrexate (M) and fluorouracil (F) (M–>F) with:
  • Surgery:
    • National Surgical Adjuvant Breast and Bowel Project [NSABP] B-13
  • Cyclophosphamide (C), M, and F with M–>F:
    • NSABP B-19
      • In patients with estrogen receptor (ER)-negative tumors and negative axillary nodes

PATIENTS AND 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% vs 59%; P < .001:
    • Was demonstrated at eight years in all B-13 patients who received M–>F:
      • 69% vs 56% [P = .006]:
        • In those < or = 49 years of age
      • 81% v 63% [P = .002]:
        • In those > or = 50 years
• A survival advantage was evident:
  • In older patients:
    • 89% v 80%; P = .03
• In NSABP B-19:
  • Through five 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 NSABP 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 NSABP B-19
  • Toxicity > or = grade 3 was:
    • More frequent among CMF patients in NSABP B-19
  • The age-related difference in CMF benefit was not related to amount of drug received

CONCLUSION: 

• 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

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