TY - JOUR
T1 - Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial
AU - Powles, Trevor
AU - Eeles, Ros
AU - Ashley, Sue
AU - Easton, Doug
AU - Chang, Jenny
AU - Dowsett, Mitch
AU - Tidy, Alwynne
AU - Viggers, Jenny
AU - Davey, Jane
N1 - Funding Information:
One reason for the difference between our data and those of the NSABP-P1 trial could relate to the study populations. Our entry criteria for all ages were predominantly based on a strong family history, with an associated increased risk of inheriting a high-risk breast-cancer-predisposing gene such as BRCA1. In our trial, using pedigree analysis, 13 we estimate that about 36% of all participants and over 60% of those who have developed breast cancer are in clusters that have a greater than 80% chance of being due to a breast-cancer-predisposition gene. In NSABP-P1, the entry criteria are based mostly on non-genetic risk factors. Oestrogen promotion, which we would be expecting tamoxifen (with its antioestrogenic effects) to oppose, may not be important in the genesis of clinical breast cancer in high-risk gene carriers. This is supported by the lack of progesterone receptors in BRCA1 and BRCA2 cancers, which indicates phenotypical hormone resistance. 14
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 1998/7/11
Y1 - 1998/7/11
N2 - Background: Tamoxifen, a drug with antioestrogenic effects, is predicted to prevent the occurrence of breast cancer. We have undertaken a trial of tamoxifen in healthy women who are at increased risk of breast cancer because of family history. We report a planned interim analysis. Methods: Between October, 1986, and April, 1996, we accrued 2494 healthy women aged between 30 and 70 with a family history of breast cancer. They have been randomised (double blind) to receive tamoxifen 20 mg per day orally or placebo for up to 8 years. Follow-up included clinical assessment, annual mammography, and assessment of toxicity and compliance. The primary endpoint was the occurrence of breast cancer, which was analysed on an intention-to-treat basis with a survival curve. Findings: With a median follow-up of 70 months, 2471 women (tamoxifen 1238, placebo 1233) were suitable for analysis. The groups were evenly matched at baseline, and compliance was good. The overall frequency of breast cancer is the same for women on tamoxifen or placebo (tamoxifen 34, placebo 36, relative risk 1.06 [95% CI 0.7-1.7], p = 0.8). Participants who were already on hormone-replacement therapy when they entered the study had an increased risk of breast cancer compared with non-users. Those participants who started such therapy while on trial had a significantly reduced risk. The safety profile of tamoxifen was as expected. Interpretation: We have been unable to show any effect of tamoxifen on breast-cancer incidence in healthy women, contrary to the report from the NSABP-P1 study showing a 45% reduction in healthy women given tamoxifen versus placebo. Differences in the study populations for the two trials may underlie these conflicting findings: eligibility in our trial was based predominantly on a strong family history of breast cancer whereas in the NSABP trial was mostly based on non-genetic risk factors. The importance of oestrogen promotion may vary between such populations.
AB - Background: Tamoxifen, a drug with antioestrogenic effects, is predicted to prevent the occurrence of breast cancer. We have undertaken a trial of tamoxifen in healthy women who are at increased risk of breast cancer because of family history. We report a planned interim analysis. Methods: Between October, 1986, and April, 1996, we accrued 2494 healthy women aged between 30 and 70 with a family history of breast cancer. They have been randomised (double blind) to receive tamoxifen 20 mg per day orally or placebo for up to 8 years. Follow-up included clinical assessment, annual mammography, and assessment of toxicity and compliance. The primary endpoint was the occurrence of breast cancer, which was analysed on an intention-to-treat basis with a survival curve. Findings: With a median follow-up of 70 months, 2471 women (tamoxifen 1238, placebo 1233) were suitable for analysis. The groups were evenly matched at baseline, and compliance was good. The overall frequency of breast cancer is the same for women on tamoxifen or placebo (tamoxifen 34, placebo 36, relative risk 1.06 [95% CI 0.7-1.7], p = 0.8). Participants who were already on hormone-replacement therapy when they entered the study had an increased risk of breast cancer compared with non-users. Those participants who started such therapy while on trial had a significantly reduced risk. The safety profile of tamoxifen was as expected. Interpretation: We have been unable to show any effect of tamoxifen on breast-cancer incidence in healthy women, contrary to the report from the NSABP-P1 study showing a 45% reduction in healthy women given tamoxifen versus placebo. Differences in the study populations for the two trials may underlie these conflicting findings: eligibility in our trial was based predominantly on a strong family history of breast cancer whereas in the NSABP trial was mostly based on non-genetic risk factors. The importance of oestrogen promotion may vary between such populations.
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U2 - 10.1016/S0140-6736(98)85012-5
DO - 10.1016/S0140-6736(98)85012-5
M3 - Article
C2 - 9672274
AN - SCOPUS:0032508294
SN - 0140-6736
VL - 352
SP - 98
EP - 101
JO - Lancet
JF - Lancet
IS - 9122
ER -