Oncology · 1998
NSABP P-1 Breast Cancer Prevention Trial (tamoxifen)
National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial
Before 1998, tamoxifen was a treatment for breast cancer, not a way to prevent it. High-risk women, those with a strong family history, prior atypical biopsies, or a calculated Gail model score above a defined threshold, had no pharmacologic option; the conversation ended at surveillance and lifestyle advice. Bernard Fisher, chairman of the National Surgical Adjuvant Breast and Bowel Project, had spent decades running adjuvant breast cancer trials and believed the same selective estrogen receptor modulator that suppressed recurrence might prevent initial tumor formation in susceptible tissue.
The NSABP P-1 trial enrolled 13,388 women at elevated breast cancer risk across multiple North American centers and randomized them to tamoxifen 20 mg daily or placebo for up to five years. The trial was stopped early after interim analysis showed a 49% reduction in invasive breast cancer incidence in the tamoxifen arm. The FDA approved tamoxifen for risk reduction in high-risk women in October 1998, acting on these data before the full follow-up was complete.
The benefit was not distributed evenly across tumor biology. Reductions occurred entirely in estrogen receptor-positive tumors; ER-negative cancers were unaffected, which aligned with tamoxifen's known mechanism and also predicted who would and would not benefit. On the other side of the ledger, tamoxifen increased rates of endometrial cancer, deep venous thrombosis, and pulmonary embolism, all more pronounced in women over 50. These findings required clinicians to weigh prevention against a concrete set of harms rather than treating chemoprevention as a simple default.
P-1 opened a clinical category that had not previously existed in oncology practice. Subsequent trials, including STAR, which compared tamoxifen to raloxifene, and later studies of aromatase inhibitors in postmenopausal high-risk women, followed directly from P-1's evidence base. The IBIS-II trial and the MAP.3 trial demonstrated that exemestane and anastrozole also reduced breast cancer incidence in high-risk postmenopausal women, extending the P-1 framework to a different drug class with a different side-effect profile.
Victor Vogel co-led the prevention program within NSABP and contributed to the risk-stratification methodology that defined trial eligibility. Uptake of tamoxifen for prevention in clinical practice remained modest despite the trial result, partly because of concerns about side effects and partly because clinicians and patients found the benefit-to-harm discussion genuinely complex in women without existing disease. The trial nonetheless established that cancer prevention by pharmacologic means was measurable, reproducible, and approvable by regulatory agencies.
Key People
- Bernard Fisher — NSABP chairman who designed and led the P-1 trial
- Victor Vogel — Co-principal investigator in the prevention program
- D. Lawrence Wickerham — NSABP co-investigator; led subsequent STAR prevention trial
J Natl Cancer Inst 1998;90:1371-1388
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