Economic Evaluation of Using a Genetic Test to Direct Breast Cancer Chemoprevention in White Women with a Previous Breast Biopsy

Abstract

Background

Tamoxifen therapy reduces the risk of breast cancer but increases the risk of serious adverse events including endometrial cancer and thromboembolic events.

Objectives

The cost effectiveness of using a commercially available breast cancer risk assessment test (BREVAGen™) to inform the decision of which women should undergo chemoprevention by tamoxifen was modeled in a simulated population of women who had undergone biopsies but had no diagnosis of cancer.

Methods

A continuous time, discrete event, mathematical model was used to simulate a population of white women aged 40–69 years, who were at elevated risk for breast cancer because of a history of benign breast biopsy. Women were assessed for clinical risk of breast cancer using the Gail model and for genetic risk using a panel of seven common single nucleotide polymorphisms. We evaluated the cost effectiveness of using genetic risk together with clinical risk, instead of clinical risk alone, to determine eligibility for 5 years of tamoxifen therapy. In addition to breast cancer, the simulation included health states of endometrial cancer, pulmonary embolism, deep-vein thrombosis, stroke, and cataract. Estimates of costs in 2012 US dollars were based on Medicare reimbursement rates reported in the literature and utilities for modeled health states were calculated as an average of utilities reported in the literature. A 50-year time horizon was used to observe lifetime effects including survival benefits.

Results

For those women at intermediate risk of developing breast cancer (1.2–1.66 % 5-year risk), the incremental cost-effectiveness ratio for the combined genetic and clinical risk assessment strategy over the clinical risk assessment-only strategy was US$47,000, US$44,000, and US$65,000 per quality-adjusted life-year gained, for women aged 40–49, 50–59, and 60–69 years, respectively (assuming a price of US$945 for genetic testing). Results were sensitive to assumptions about patient adherence, utility of life while taking tamoxifen, and cost of genetic testing.

Conclusions

From the US payer’s perspective, the combined genetic and clinical risk assessment strategy may be a moderately cost-effective alternative to using clinical risk alone to guide chemoprevention recommendations for women at intermediate risk of developing breast cancer.

Appendix

1.1 Calculation of Combined Risk

The combined risk of breast cancer was calculated as follows. For each risk allele i with frequency f _i and per allele odds ratio r _i , the risk of breast cancer due to this allele relative to the population mean risk was calculated as $\frac{{r_{i}^{2} }}{{n_{i} }}$ for individuals with two copies of the risk allele, $\frac{{r_{i} }}{{n_{i} }}$ for individuals with one copy of the risk allele, and $\frac{1}{{n_{i} }}$ for individuals with no copies of the allele, where $n_{i} = r_{i}^{2} \cdot f_{i}^{2} + 2r_{i} \cdot f_{i} \cdot (1 - f_{i} ) + 1 \cdot (1 - f_{i} )^{2}.$ The combined risk score was computed by multiplying the individual’s Gail 5-year risk by the product of these relative risks for each of the seven alleles. For example, if a woman had a Gail 5-year risk of 1.5 %, and had two copies each of the risk-bearing alleles of rs2981582 and rs3803662, one copy each of the risk-bearing alleles of rs889312, rs13387042, and rs13281615, and no copies of risk-bearing alleles of rs4415084 or rs3817198, then her combined risk score would be 1.5 %*1.31*1.31*1.05*0.99*1.01*0.88*0.96 = 2.28 %. See Table 8.

Table 8 Calculation of risk multipliers