Swedish Two-County Trial

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Tabar L, et al. "Swedish two-county trial: impact of mammographic screening on breast cancer mortality during 3 decades". Radiology. 2011. 260(3):658-663.
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Clinical Question

What is the the long-term (29-year) effect of mammographic screening for women age 40-74 on breast cancer mortality?

Bottom Line

Mammography screening of women starting at 40 results in a highly significant decrease in breast cancer–specific mortality.

Major Points

The Swedish Two-County Trial of mammographic screening was the first breast cancer screening trial to show that mortality from breast cancer was reduced from screening with mammography alone.[1] The trial began in 1977 and enrolled 162 981 women aged 40 years or more and living in the counties of Kopparberg and Ostergötland in Sweden. The women were randomly divided into 2 groups: one group invited for single view mammography screening every 2 to 3 years, and the other group that was not invited for screening. The first published results to the end of 1984 showed a 31% reduction in mortality from breast cancer and a 25% reduction in the rate of stage II or more advanced breast cancers in the group invited to screening.

Since the initial published results, regular updates of the trial have shown that the effect of screening on breast cancer mortality has remained stable over longer follow-up.[2][3][4] In addition, the absolute benefit in terms of lives saves increased over time. The purpose of this 29 year follow-up was to estimate the long term mortality in terms of relative and absolute effects.

Case status and cause of death was determined by a local trial committee and an independent Swedish overview committee through local end point trial data and national registry data. Results from the Swedish overview committee consensus data show a significant reduction in breast cancer mortality (RR 0.73; 95% confidence interval: 0.59, 0.89; P=.002). These were within >10% of local end point committee data (RR 0.69; 95% confidence interval: 0.56, 0.84; P=<.0001). The number of women needed to undergo screening for 7 years to prevent one death was 414 according to local data and 519 according to consensus data.

However, results from a 25 year follow-up of the Canadian National Breast Screening Study have called into question the benefit of early breast cancer screening.[5]

Not all health organizations agree on breast cancer screening guidelines. The U.S. Preventive Services Task Force mammogram guidelines recommend women begin screening at age 50 and repeat the test every two years. The American Cancer Society and other organizations recommend screening begin at 40 and continue annually.

Guidelines

American Cancer Society

  • Mammography screening beginning at age 40 and continuing annually in healthy women.

U.S. Preventive Services Task Force

  • Mammography screening beginning at age 50 and repeating every 2 years.

Design

  • Two center, randomized, controlled trial
  • N=133,065
    • Invited for screening (n=77,080)
    • Control (n=55,985)
  • Setting: 2 centers in Sweden
  • Enrollment: From 1977 in Dalarna for 31 months, and 1978 in Östergötland for 34 months.
  • Mean follow-up: 29 years
  • Analysis: Intention-to-treat
  • Primary outcome: mortality from breast cancer

Population

Inclusion Criteria

  • Women age 40 to 74
  • Residing in one of two counties in Sweden: Dalarna and Östergötland

Exclusion Criteria

  • Women with previously diagnosed breast cancer

Interventions

  • Female population from the two counties were divided into 45 geographic clusters. The population in these clusters were randomized to invited (mammography screening for breast cancer) or control (no mammography screening).
    • The invited/control randomization ratio was approximately 1:1 in Östergötland and 2:1 in Dalarn
    • Women aged 40– 49 years at randomization were invited to screening every 24 months on average.
    • Women aged 50–74 years were invited to screening every 33 months on average.
    • The screening method was one-view screen-film mammography with a single reading—without physical examination.
  • Case status and cause of death was determined by a committee of physicians after a detailed review of patient's records and autopsy data.

Outcomes

Comparisons are invited for screening and control group

Primary Outcomes

Local Trial End Point Committee Data
Breast Cancers Detected/Deaths
351/1426 vs. 367/1042 (RR 0.69; 95% confidence interval: 0.56, 0.84; P=<.0001)
Swedish Overview Committee Consensus Data
Breast Cancer Deaths
39/1439 vs. 339/1049 (RR 0.73; 95% confidence interval: 0.59, 0.89; P=<.0001)

Criticisms

  • Trial used only single-view, single-observer screenings, with longer intervals than in other trials.
  • Inconsistencies between the assessment of cause of death in the trial and the official Swedish cause of death register data.

Funding

  • American Cancer Society through a gift from the Longaberger Company’s Horizon of Hope Campaign

Further Reading

  1. Tabar, Lazio, et al. "Reduction in mortality from breast cancer after mass screening with mammography: randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare." The Lancet 325.8433 (1985): 829-832.
  2. Tabar, Laszlo, et al. "The Swedish two county trial of mammographic screening for breast cancer: recent results and calculation of benefit." Journal of epidemiology and community health 43.2 (1989): 107-114.
  3. Tabar, Laszlo, et al. "Efficacy of breast cancer screening by age. New results swedish two‐county trial." Cancer 75.10 (1995): 2507-2517.
  4. Tabár, László, et al. "The Swedish Two-County Trial twenty years later: updated mortality results and new insights from long-term follow-up." Radiologic Clinics of North America 38.4 (2000): 625-651.
  5. Miller, Anthony B., et al. "Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial." Bmj 348 (2014).