Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P‑1 Study
Tamoxifen reduces the risk of invasive breast cancer by 49 % and is an effective preventive agent for women at increased risk of breast cancer.
Background: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P‑1) in 1992. Methods: Women (N = 13 388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35‑59 years of age with a 5‑year predicted risk for breast cancer of at least 1.66 %, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n = 6 707) or 20 mg/day tamoxifen (n = 6 681) for 5 years. Gail's algorithm was used to estimate the probability of occurrence of breast cancer over time. Results: Tamoxifen reduced the risk of invasive breast cancer by 49 % (two‑sided P<.00001), with cumulative incidence through 69 months of follow‑up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44 %), 50‑59 years (51 %), and 60 years or older (55 %); risk was also reduced in women with a history of lobular carcinoma in situ (56 %) or atypical hyperplasia (86 %) and in those with any category of predicted 5‑year risk. Tamoxifen reduced the risk of non‑invasive breast cancer by 50 % (two‑sided P<.002). Tamoxifen reduced the occurrence of estrogen‑positive tumors by 69 %, but no difference in the occurrence of estrogen‑negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95 % confidence interval = 1.35‑4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep‑vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. Conclusions: Tamoxifen decreases the incidence of invasive and non‑invasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.
Demonstrating that a widely available drug can reduce breast cancer incidence in high‑risk women provides a tangible prevention strategy and informs decisions about initiating prophylactic therapy, while balancing the benefits against documented adverse events.
Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
Kapcsolódó jelek
- 20‑Year Risks of Breast‑Cancer Recurrence after Stopping Endocrine Therapy at 5 Years
- Breast Cancer: The good, the bad, and an important call to effective risk reduction strategies
- Clinical Trials in Cancer - Transforming Clinical Research in the United States - NCBI Bookshelf
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- The SURVIVE study (NCT05658172): Bringing breast cancer aftercare to the 21st century: Study protocol of a Phase III clinical trial comparing liquid biopsy guided vs. Standard of care surveillance for intermediate to high-risk breast cancer survivors - PMC