- 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
- Recurrence free survival (RFS):
- Tamoxifen-treated patients were found to have benefited irrespective of age, menopausal status, or ER concentration for:
- 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
- This included a:
- 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
- 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:
- 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
- Significant survival advantage with the addition of endocrine therapy to:
-
To determine if there was a:
- To five years of tamoxifen or
5 years of placebo:
- 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
- 69% vs 57%
- With the use of tamoxifen for 5 years:
- With a 37% reduction:
- In the rate of contralateral breast cancer (P=0.007)
- A statistically significant DFS benefit was derived:
- The most recent update of this trial:
- Continues to demonstrate this survival benefit at 15 years:
- Irrespective of age
- Menopausal status
- Tumor ER concentration
- Continues to demonstrate this survival benefit at 15 years:
- 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
- 90% vs 96%, P=0.01:
- DFS:
- There was a significant disadvantage in:
- Five additional years of tamoxifen or
five years of placebo
- The same patient population was then re-randomized to:
- Asked the recommended duration of tamoxifen therapy beyond 5 years:
- Randomized patients after surgery to:
- 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.
NSABP B-14
Rodrigo Arrangoiz MS, MD, FACS, FSSO 