• The NSABP B14 trial was a randomized, double blind, placebo-controlled trial:
    • Of postoperative therapy with tamoxifen (10 mg BID) in 2644 patients with ER positive histologically node-negative breast cancers
    • Patients were administered the drug for at least 5 years
    • After 15 years of follow-up, compared with placebo:
      • Tamoxifen-treated patients were found to have benefited irrespective of age, menopausal status, or ER concentration for:
        • Recurrence free survival (RFS):
          • 78% tamoxifen vs. 65% placebo
        • Overall Survival (OS):
          • 71% tamoxifen vs. 65% placebo
    • A multivariate analysis indicated that all subgroups investigated showed benefit from tamoxifen treatment:
      • This included a:
        • Reduction in rate of treatment failure at local and distant sites
        • A reduction in rate of incidence of new tumors in the contralateral breast
        • A reduction in loco-regional recurrence after lumpectomy and breast irradiation
    • While NSABP B-14 is known for establishing tamoxifen as an effective adjuvant therapy in ER positive, node-negative patients:
      • Disease-free survival and OS were found to decrease over the 15-year follow-up in a subset of patients originally thought to have a favorable prognosis
      • These findings prompted researchers to find a way to optimize treatment in this group:
        • Thus, the NSABP conducted the B-20 trial to evaluate the value of adding chemotherapy to tamoxifen for treatment regimens in ER positive, node-negative patients:
          • Results from the B-20 trial after a 12-year follow-up demonstrated a significant improvement in disease-free survival with the addition of chemotherapy to tamoxifen when compared to tamoxifen alone
  • NSABP B-14:

    • Randomized patients after surgery to:

      • To five years of tamoxifen or 
5 years of placebo:
To determine if there was a:

          • Significant survival advantage with the addition of endocrine therapy to:
            • ER-positive tumors
    • After 10 years of follow-up:

      • A statistically significant DFS benefit was derived:

        • With the use of tamoxifen for 5 years:

          • 69% vs 57%
            • P<0.0001

      • With a 37% reduction:
In the rate of contralateral breast cancer (P=0.007)

    • The most recent update of this trial:

      • Continues to demonstrate this survival benefit at 15 years:
        • Irrespective of age
        • Menopausal status
        • Tumor ER concentration
    • A follow-up question to protocol B-14:

      • Asked the recommended duration of tamoxifen therapy beyond 5 years:

        • The same patient population was then re-randomized to:

          • Five additional years of tamoxifen or 
five years of placebo

            • There was a significant disadvantage in:

              • DFS:

                • 86% vs 92%, P= 0.003 and 

              • Distant DFS:

                • 90% vs 96%, P=0.01:

                  • For patients who continued tamoxifen for more than 5 years versus those who took it for only 5 years

                  • The lack of benefit with additional tamoxifen use was independent of patient age
  • References:
    • Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, et al. A randomized trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor positive tumors. N Engl J Med. 1989;320(8):479-484.
    • Fisher B, Jeong JH, Bryant, Anderson S, Dignam J, Fisher ER, et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. Lancet. 2004;364(9437):858-868.
    • Newman LA, Mamounas EP. Review of breast cancer clinical trials conducted by the National Surgical Adjuvant Breast Project. Surg Clin N Am. 2007;87(2):279-305.

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