An analysis of mass screening strategies using a mathematical model: comparison of breast cancer screening in Japan and the United States

Abstract

Background: Although the United States Preventive Services Task Force (USPSTF) downgraded their recommendation for breast cancer screening for women aged 40-49 years in 2009, Japanese women in their 40s have been encouraged to attend breast cancer screenings since 2004. The aim of this study is to examine whether these different mass-screening strategies are justifiable by the different situations of these countries and to provide evidence for suitable judgment.

Methods: Performance of screening strategies (annual/biennial intervals; initiating/terminating ages) was evaluated using a mathematical model based on the natural history of breast cancer and the transition between its stages. Benefits (reduced number of deaths and extended average life expectancy) and harm (false-positives) associated with these strategies were calculated.

Results: Additional average life expectancy by including women in their 40s as participants were 13 days (26%) and 25 days (22%) in Japan and the United States, respectively, under the biennial screening condition; however, the respective increases in numbers of false-positive cases were 65% and 53% in Japan and the United States. Moreover, the number of screenings needed to detect one diagnosis or to avert one death was smaller when participants were limited to women of age 50 or over than when women in their 40s were included. The validity of including women in their 40s in Japan could not be determined without specifying the weight of harms compared to benefits.

Conclusions: Whether screening of women in their 40s in Japan is justifiable must be carefully determined based the quantitative balance of benefits and harms.

Figure 1.. A mathematical model of breast cancer screening consisting of 12-month cycles of 10 health states that simulate the theoretical natural history of breast cancer, comprising the following seven structures: u₁: healthy; w₁: false positive; u₂–u₅: undetected breast cancer (stages 1–4); w₂–w₅: detected for breast cancer (stages 1–4) through screening or outpatient care; du₁: died from a cause other than breast cancer; du₂–du₅^a: undetected and died of breast cancer; dw₁–dw₄^a: detected and died of breast cancer. Stage classifications used here are those published by the Union for International Cancer Control (UICC) for Japanese data and by the American Joint Committee on Cancer (AJCC) for United States data. ^aDeath from causes other than breast cancer (μ) is excluded. BC, breast cancer.

Figure 2.. Model-predicted and observed statistics on age-specific incidence (a), mortality (b), and stage distribution of breast cancer (c) in Japan and the United States. A population of 100 000 women was traced from age 0 to 100 years. Observed statistics on incidence^a peaked (154.5 per 100 000 women) in those age aged 45–49 years in Japan, whereas the incidence increased continuously from age 45 and peaked (433.1 per 100 000 women) in those aged 75–79 years in the United States. Observed statistics on mortality tended to increase with age in both Japan and the United States. Differences in mortality between Japan and the United States were marked in women aged 50 years or older. ^aExcluding carcinoma in situ.

Figure 3.. Average life expectancy extension in 40-to-74-year age group (vs. 50–74 years) in Japan and the United States; (a) absolute effect; (b) relative effect^a. ^aRelative effect of average life expectancy extension was calculated; in Japan, eg, 26% [(63 − 50 = 13 days)/50 days × 100] (δ′ = 1.5δ).