New analyses from researchers at Queen Mary University of London (UK) have indicated that tamoxifen can reduce the chances of breast cancer development by approximately 30%, and that this effect can remain almost constant for at least 20 years. The study, which was funded by Cancer Research UK, was presented at the San Antonio Breast Cancer Symposium (December 9–13, TX, USA) and recently published in The Lancet Oncology.
The International Breast Cancer Intervention Study-I trial (IBIS-I) studied the long-term effects, both risks and benefits, of patients taking tamoxifen as a form of prevention against breast cancer. The individuals chosen for the study were all women considered to be at high risk of developing the disease; 35–70 years of age and predominantly with a family history of breast cancer.
The study consisted of 7154 pre and post-menopausal women who were randomized to receive either 20 mg daily of tamoxifen or a placebo for 5 years. Subsequent to the full treatment the research team monitored the health of all women within the study, with an average follow-up time of 16 years and a maximum of 22 years.
This extended analysis identified a 29% reduction in the development of breast cancer in women who had received tamoxifen compared with those that had not. Of the 7154 participants, 251 women in the tamoxifen group and 350 from the placebo group developed breast cancer. In addition to this estrogen receptor-positive invasive cancer was reduced by 35%.
The estimated risks of developing breast cancer were 8% and 12% after 20 years of follow-up for the tamoxifen and placebo groups, respectively. This equates to 22 women being treated with tamoxifen for every one breast cancer case prevented after 20 years.
Jack Cuzick (Queen Mary University of London), lead author of the study, commented: “Tamoxifen is a well-established and effective treatment for certain breast cancers, but we now have evidence of its very long-term preventive benefits. The preventive effect of tamoxifen is highly significant with a reduction in breast cancer rates of around a third, and this impact has remained strong and unabated for 20 years. We hope these results will stimulate more women, particularly younger women, to consider treatment options for breast cancer prevention if they have a family history of the disease or other major risk factors.”
Within the study, hormone replacement therapy was also demonstrated to have an impact on the effectiveness of tamoxifen as a preventative agent, highlighting a significantly reduced benefit in participants who were also prescribed hormone replacement during the 5 year tamoxifen treatment period. Moreover, the incidence of endometrial cancer, which is a known side effect of tamoxifen, was 3.8 times more common in tamoxifen patients during the five year treatment period (15 tamoxifen versus 4 placebo). However, there was no evidence of increased risk in the follow-up period.
Despite these results, an effect of tamoxifen treatment on breast cancer-specific deaths has not been illustrated so far. To date, there have been 31 breast cancer-related deaths in the tamoxifen group, compared with 26 in the placebo group. Additionally, there have been five deaths due to endometrial cancer in the group of women receiving tamoxifen treatment. Deaths due to other causes totaled at 146 and 140 for the tamoxifen and placebo groups, respectively.
Cuzick continued: “Despite a clear and continuing reduction in breast cancer rates, this has not yet resulted in a reduction in breast cancer deaths. However, the number of deaths is still small compared with the number of breast cancer cases – which is 10 times higher. We will need to continue monitoring these women for a further decade to get a clearer picture of the impact of tamoxifen on death rates. Some of the side effects of tamoxifen are also cause for concern and need continued monitoring – specifically the increased occurrence of endometrial cancer.”
These results follow on from the release of the IBIS-II trial results last year, which indicated that the aromatase inhibitor anastrozole could reduce the likelihood of postmenopausal high-risk women developing breast cancer by 53%, compared with those taking a placebo.
Despite these findings, tamoxifen remains the only drug option for the majority of premenopausal high-risk women. The evidence from the IBIS-I trial importantly shows that tamoxifen is an effective drug for breast cancer prevention.
Julie Sharp (Cancer Research UK) added: “The landmark IBIS trials show the value of chemoprevention for women at high risk of breast cancer and highlight just how important these large and long-term studies are. This follow up of IBIS-I confirms that tamoxifen has a long-lasting effect in reducing cases of breast cancer in women at high risk of the disease. All these drugs have side effects so it’s important that women at high risk of breast cancer talk through their choices with their doctor to work out the best option for them.”