New Evidence May Tip Balance Towards Taking Tamoxifen to Prevent Breast Cancer

A new study in the  journal Cancer, published by the American Cancer Society concludes that tamoxifen can save lives and decrease medical costs when taken by menopausal women under 55 years of age as a preventive measure against breast cancer (DOI: 10.1002/cncr.25926).

The conclusion is based on results of simulated virtual “5 year trials” using a mathematical model that accounts for known breast cancer incidence, tumor growth, detection, and progression, and various risk groups.

Tamoxifen is an oral anti-estrogen that, besides being used as a treatment for breast cancer for over 30 years, is also used to reduce the chance of breast cancer development in women who have an increased risk of the disease. It was approved as a preventive agent by the FDA based on a trial published in 1998 that showed a 50% reduction in risk of invasive breast cancer. The eligible high-risk cohort of women, however, does not often take prophylactic tamoxifen due to the accompanying side effects of thromboembolitic events, cataracts, and higher susceptibility to endometrial cancer. Additionally, cost-effective analyses suggested that tamoxifen as a breast cancer prevention agent is not cost-effective.

New long-term tamoxifen trial data calls previous cost-effectiveness analyses into question
The authors of the paper state that the cost analysis question needed to be re-evaluated in light of recent results of long-term, 20-year, and 8-year follow-up tamoxifen prophylaxis cancer trials. The new long-term data suggest that tamoxifen can actually protect against breast cancer for years after discontinuation of tamoxifen. However, identifying the cohort of women for whom the benefit outweighs the risk of treatment is still a formidable challenge. 

Using their mathematical model, the authors modeled five-year virtual placebo-controlled trials comparing tamoxifen treatment with no treatment in post-menopausal women 55 years of age and under. The trials were modeled on four randomized, controlled cancer preventive trial results and evaluated the effects of the treatment on breast cancer risk for 10 years after treatment discontinuation.

Study results show cost-effectiveness of prophylactic tamoxifen
The simulation results reaffirm the utility of tamoxifen in women at high risk of breast cancer development. Women with a greater than 1.66% five-year risk of breast cancer development receive a maximal benefit from the treatment, with minimal side effects. This is the specific cohort for which the American Society of Clinical Oncology recommends tamoxifen as prophylaxis. “Specifically, chemoprevention with tamoxifen prevents 29 breast cancer cases and 9 breast cancer deaths per 1,000 women treated, and it saves $47,580 per 1,000 women treated in the United States,” stated one of the study authors, Dr. Alperin, MD, of Archimedes Inc. in San Francisco.

The caveat is that the model is only for estrogen-receptor (ER)-positive breast cancer and does not account for the 2-10% of the population that does not respond to tamoxifen treatment. However, this study is a step forward in assisting physicians in making an educated decision for patients at high risk of breast cancer. It will also facilitate further study for understanding the risk factors that influence tamoxifen side effects as well as the total duration of breast cancer risk reduction with tamoxifen, which is still unknown.