Breast cancer is the most frequently diagnosed cancer among women. Its rate of incidence in the United States has continued to increase since 1986
[WTHR03], while breast cancer mortality has decreased overall in the United States, Canada and the United Kingdom [SEER98, IARC99, WTHR03]. Plausible explanations for this decrease in mortality include progress in treatment, as well as widespread participation in early detection programs that contribute to increased cure rates and reduced disease-specific mortality. Many studies have indicated that early detection through screening can lead to more advantageous treatment options, and often leads to an increase in survival rates and improvement in the quality of life for women who develop breast cancer [FE03, Wan03]. The development of new technologies and further improvement of the existing modalities for disease detection may increasingly make screening for cancer a routine part of secondary prevention.
The goals of early detection are to reduce breast cancer morbidity and mortality. Optimal screening strategies are expected to carefully balance these goals against the associated burden to women and cost to health care systems. Several issues regarding the optimal choice of breast cancer screening strategies remain open. For example, debate surrounds the question of whether regular mammographies are beneficial to women in their forties. Evidence of benefit varies across the relevant randomized clinical trials [Ber9], and there is controversy on the relevance of the suggested benefits for individual women. Consensus panels [GBC97, CTF01] who reviewed the evidence did not find it sufficiently strong to make general recommendations, emphasizing that "women should be informed of the potential benefits and risks of screening mammography and assisted in deciding at what age they wish to initiate the manoeuvre" [CTF01]. In addition to the issue of the appropriate age at which screening should begin, complex open issues include the appropriate frequency of screening examinations; whether women who are at increased risk of breast cancer would benefit from more frequent screening; and what would be the impact of combining multiple screening modalities.
Evaluating alternative screening strategies is difficult because the benefits of screening depend on complex interaction among several factors, including the ability of various screening tests to detect cancer sufficiently early; the time window during which such detection can take place, and its relation to the interval between screening exams; the relative advantage of an early detection compared to waiting for symptoms to arise; the age distribution of onset of pre-symptomatic cancer; competing causes of mortality; and others.
Simulation-based decision models have proved to be an effective way to evaluate health care interventions whose consequences are complex and depend on the interaction of many factors. They can provide a formal structure for supporting optimal choice of screening strategies, cost-effectiveness analysis of specific interventions, and formal optimization of utility functions of interest. These models often generate simulated individual histories by drawing evidence from several sources, including epidemiology and genetic risk factors, relevant clinical trials of secondary prevention and treatment, and studies of tumor growth. A decision model can also support realistic assessments of uncertainty about the relative merits of alternative choices, an aspect that is often underappreciated in policy making [Par02]. The literature on modelbased evaluation of screening strategies is now extensive [VBH95, PARM02].
In this article we consider the model by Parmgiani [Par93, Par02], and generalize it by incorporating the possibility of using two breast cancer screening modalities in concert: mammography (MM) and clinical breast examination (CBE). We also update the model inputs to reflect recent contributions to the literature. Existing investigations regarding the balance between mortality reduction and costs have focused on mammography only, and have paid less attention to the combined use of periodic mammography with clinical breast examination. [Dek00, LR95, Bro92, MF92, VVD93, Bro92, BF93, Eli91, Cla92, PK93, EHM89, CGV93, SKP97, BBE01, Fet01, YRP03, KSR03]. Recent studies have shown that periodic clinical breast examinations combined with mammograms improve the overall sensitivity of the screening exam compared with mammography alone, [BHF99, BMB99, BLT00, SZ01], and can be particularly valuable among younger women for whom the sensitivity of mammography alone is relatively low. Logistically, a regular clinical breast examination is easy to administer as part of a routine physical examination, and is less expensive compared to mammography.
To promote more efficient and cost-effective breast cancer early detection programs, we will explore optimal screening strategies in terms of the costs and the quality-adjusted years of life saved. The analyses focus on strategies that combine the use of both mammography and clinical breast examination. The other factors we investigate include age group and screening interval. The primary objectives of this article are to discuss modeling issues arising in optimization of screening strategies with multiple modalities, and to provide methodologic justifications for models and sources of data used in the analyses reported Shen and Parmigiani [SP05].
The results from our investigation will help in the design of more efficient and near optimal early detection programs, thereby maximizing the survival benefit for breast cancer patients while also considering the associated societal costs. This study focuses on breast cancer, but the methods are also applicable to early detection programs for other types of cancer. The proposed research will provide a basis to guide health policy makers in designing optimal and cost-effective screening programs, and in extending such benefits to a large population.
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