New study examines cost savings, chemoprevention aspects of tamoxifen

Virtual clinical trial model suggests group of women most likely to benefit from taking tamoxifen as a cancer prevention agent

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According to a new study run by Archimedes Inc. and published online in Cancer, a peer-reviewed journal of the American Cancer Society, taking tamoxifen as a preventative against breast cancer can both save lives and reduce medical costs. Tamoxifen, an estrogen receptor blocker, has been used as a treatment for women with breast cancer for decades, and recently, it has been noted just how long tamoxifen continues to have a suppressing effect on cancer post-treatment.

The issue, however, is that it's been difficult to pinpoint which group of women can most benefit from tamoxifen without serious side effects, which include cataracts, deep vein thrombosis, endometrial cancer and pulmonary embolism, in addition to hot flashes and early menopause. Still, tamoxifen's long history, as well as its potential in the prevention of breast cancer, led Archimedes to analyze the drug with an eye toward which kinds of patients would benefit most from its preventative capabilities.

"There's been a ton of trials, and what they noticed was that in addition to reducing recurrence in the same affected breast, it also had significant reduction in contralateral breast cancer," says Joyce Noah-Vanhoucke, lead author of the study and a scientist at Archimedes. "And they sort of extrapolated from that and said 'oh, maybe we can use it as a chemopreventive agent.'"

Dr. Peter Alperin, Archimedes' vice president of medicine and the study's co-author, along with his colleagues, used the Archimedes Model to simulate a population of post-menopausal women under the age of 55 in a virtual clinical trial, in which they compared patients being treated with tamoxifen with those receiving no treatment. Scientists modeled the virtual therapy based on the analysis of four randomized, placebo-controlled cancer prevention trials, and also studied the effect the drug would have on breast cancer risks 10 years after treatment. The trial used cancer incidences and survival information from the Surveillance Epidemiology and End Results cancer registry, and factors such as quality of life, cost and non-cancer disease incidences were taken from medical literature.

Archimedes describes their model as "a full-scale simulation model of human physiology, diseases, behaviors, interventions and healthcare systems." It consists of hundreds of equations and algorithms that together represent real patient physiology and healthcare situations.

"We use our model to sort of model out the complex interplay between the factors which increase your risks and then the factors of the side effects, as well as the things that increase your risk of developing disease," Alperin says, "and that's how it is that we came up with this group of people who would seem to benefit the most."

The study illustrated that post-menopausal women 55 years old and younger with a five-year risk of developing breast cancer of 1.66 percent or greater would benefit from taking tamoxifen the most, with the drug's chemopreventive benefits maximized and its side effects minimized.

"In this group of women, using tamoxifen to prevent breast cancer saves lives and has a low frequency of side effects," says Alperin. "Specifically, chemoprevention with tamoxifen prevents 29 breast cancer cases and nine breast cancer deaths per 1,000 women treated, and it saves $47,580 per 1,000 women treated in the United States."

Noah-Vanhoucke notes that as the risk threshold was lowered in the study and more women were included, "you get a benefit and risk ratio that approaches 1-to-1." She adds that in none of the demographic groups did they see "more side effects than breast cancer cases prevented, but they were comparable to each other" as the risk threshold was lowered. Alperin cautions that when looking at drugs given on a chemopreventive basis, "it's really critical that the risk/benefit ratio be pretty strongly swung in favor of the benefits and not the risks."

"It's another thing to say that you're going to be getting a medication for something you already have, but if you're giving it again for a chemopreventive agent, even if you're at increased risk, you always have to be very careful about how one addresses that risk/benefit ratio," Alperin stresses.

Alperin notes that Archimedes is seeing "a pretty robust adoption of our technology" of late, and that their model "is gaining a lot of traction inside of the industry," reflecting the more cautious attitude seen lately in the pharmaceutical industry as more companies seek risk-sharing opportunities and carefully consider their investments.

"As the financial investments increase for development of new compounds, I think groups are being very careful and just a bit more cautious about doing more modeling," Alperin says, "so that they can understand what might happen with these drugs not only in the clinical trial populations that they may enroll, but also in the populations of patients who actually they think will end up getting their compound after the drug is approved."

There's a definite niche for forecasting models such as Archimedes' and for chemopreventive therapies such as tamoxifen. As scientists and doctors learn more about the various forms of cancer, more information is released about lifestyle changes that can prevent or at least reduce the risk of cancer, and while there are a multitude of treatments available for those afflicted, it's looking more and more like the best bet against the disease is prevention.

"There is a desire to push more effort towards prevention of cancer in the first place," says Noah-Vanhoucke. "It's hard to speculate as to the future, but if we look at tamoxifen as a case study, that really came out of using tamoxifen for treatment that we learned about its chemopreventive properties."

The study, entitled "Cost-effectiveness of chemoprevention of breast cancer using tamoxifen in a postmenopausal US population," was published online March 14. Additional co-authors for the study include Drs. Linda E. Green, Tuan A. Dinh and Robert A. Smith.

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