A long-term follow up study has reported on the effectiveness of tamoxifen for breast cancer prevention in women at high risk for developing breast cancer. The international breast cancer intervention study reported significant reductions in breast cancer cases for up to 20 years in women who took tamoxifen for 5 years, compared with women who did not.
Tamoxifen prevents the growth of breast cancer cells by competitively binding to and preventing the activation of the estrogen receptor, which drives the growth of breast cancer cells. Because it is an estrogen receptor antagonist, tamoxifen only inhibits the growth of estrogen receptor-positive breast cancer cells, and not estrogen receptor-negative breast cancer cells. Tamoxifen is used, therefore, to treat estrogen receptor-positive breast cancer in women; however, tamoxifen has also been investigated as a preventive medicine in women at high risk of developing breast cancer.
The International Breast Cancer Intervention Study I (IBIS-I) has reported in the Lancet results from 20 years of follow up. The IBIS-I study began in 1992 at 37 medical centres in the UK, Australia, NZ, Finland, Spain, Switzerland, Belgium, and Ireland. Women considered to be at high risk of developing breast cancer; either having a family history of breast cancer, or abnormal benign breast disease, were randomly allocated to receive either 20mg per day of tamoxifen or placebo control for five years.
Earlier reports from the IBIS-I study demonstrated significant reductions in incidence of estrogen receptor positive breast cancer in women taking tamoxifen. These results were reported during the first 10 years of follow up. The current report after 20 years of follow up demonstrated that, overall, the risk of breast cancer in the treatment group was 7.8%, compared with 12.3% in the control group. There was an overall reduction in the incidence of breast cancer for up to 20 years following the 5 year treatment period; however, this reduction in incidence did not result in a reduction in mortality in the treatment group.
Although the study indicates success in relation to estrogen receptor positive cancers, Tamoxifen did not reduce the incidence of estrogen receptor negative breast cancers; in fact, there were more estrogen receptor negative breast cancers in the tamoxifen treatment group compared with the placebo group. In addition, tamoxifen was not as effective at preventing breast cancer in women who were also taking hormone replacement therapy while they were taking tamoxifen. An adverse effect reported by this and other tamoxifen trials is an increase in the incidence of endometrial cancer during the time that the women were taking tamoxifen, which also resulted in increased mortality in this group of women.
As with any medical treatment, the harm versus benefit should be weighed carefully when considering the potential benefits of breast cancer prevention versus the associated risks in this group of high-risk women.
Cuzick, J, Sestak, I, Cawthorn, S, Hamed, H, Holli, K, Howell, A, Forbes, JF, on behalf of the IBIS-I Investigators “Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial” The Lancet Oncology, early online publication DOI: http://dx.doi.org/10.1016/S1470-2045(14)71171-4 Published Online: 11 December 2014.
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Written by Deborah Tallarigo, PhD