Tamoxifen Breast Cancer Prophylaxis Offers ‘Very Long Period of Protection’

The breast cancer risk reduction associated with prophylactic tamoxifen lasts over 10 years

medwireNews: Women given 5 years of treatment with tamoxifen to combat an excess risk of breast cancer have benefited throughout the extended follow-up period of the IBIS-I breast cancer prevention trial, researchers say.

After a median of 16 years of follow-up, 7.0% of the 3579 patients who were randomly assigned to receive tamoxifen 20 mg/day on the basis of family history or benign breast disease were diagnosed with breast cancer compared with 9.8% of the 3575 women assigned to receive placebo, giving a significant hazard ratio (HR) of 0.71.

And the reduction in the risk of breast cancer diagnosis associated with tamoxifen versus placebo was comparable for the first 10 years of the study (6.3 vs 4.6%, HR=0.72) and thereafter (3.8 vs 2.6%, HR=0.69), report Jack Cuzick, from Queen Mary University London, UK, and team.

“These results show that tamoxifen offers a very long period of protection after treatment cessation”, they write.

Further analysis indicated that tamoxifen was significantly associated with a reduction in the likelihood of developing invasive Oestrogen receptor (ER)-positive breast cancer (HR=0.66) and ductal carcinoma in situ (HR=0.65), but no such protective effect was found for invasive ER-negative disease.

Age did not significantly impact on the protective effect of tamoxifen, but women who used hormone replacement therapy for the menopause during tamoxifen treatment derived significantly less protection against breast cancer than those who did not. Hormone therapy had the greatest impact on the reduction of the risk of invasive ER-positive disease (HR=0.87 for users vs 0.55 for nonusers).

Jack Cuzick et al note with “some concern” that tamoxifen did not significantly impact on the risk of breast cancer-specific mortality, but observe that the study was underpowered for this analysis.

As previously reported for adjuvant tamoxifen trials, there was a trend towards an increase in the first 10 years of follow-up for the risk of endometrial cancer death with tamoxifen (five vs 0 cases).

The researchers say this finding “is important in making the decision to use the drug” but nevertheless conclude that the extended IBIS-I results “substantially improve the benefit-to-harm ratio for the use of tamoxifen to prevent breast cancer in high-risk women.”

The study has been simultaneously reported at the San Antonio Breast Cancer Symposium in Texas, USA, and as an advance early publication in The Lancet Oncology.


Cuzick J, Sestak I, Cawthorn S, et al. Tamoxifen for the prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol 2014; Early online publication 11 December. doi:10.1016/S1470-2045(14)71171-4

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