OB/GYN Quarterly Update

Does availability of screening mammography significantly reduce breast cancer mortality?

Abstract & Commentary

By Jeffrey T. Jensen, MD, MPH, Editor, OB/GYN Clinical Alert, also published by AHC Media, and Leon Speroff, Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland.

Synopsis: The availability of screening mammography in Norway did not result in a significant reduction in breast cancer mortality after subtracting the effect of improved cancer treatment.

Source: Kalager M, Zelen M, Langmark F, et al. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med 2010; 363:1203-1210.

To assess the effect of screening mammography on breast cancer mortality, the authors used data from the Norwegian Breast Cancer Screening Program to observe chronologic trends associated with screening as well as advances in breast cancer awareness and treatment. The Norwegian Breast Cancer Screening Program offered women between the ages of 50 and 69 years screening mammography every two years. The authors compared the incidence-based rates of death from breast cancer in four groups: two groups of women that from 1996 through 2005 were living in counties with screening (screening group) or without screening (nonscreening group); and two historical comparison groups that from 1986 through 1995 mirrored the current groups.

Analyzing data from 40,075 women with breast cancer, the death rate was reduced by 7.2 deaths per 100,000 person-years in the screening group as compared with the historical screening group (rate ratio [RR], 0.72; 95% confidence interval [CI], 0.63-0.81) and by 4.8 deaths per 100,000 person-years in the nonscreening group as compared with the historical nonscreening group (RR, 0.82; 95% CI, 0.71-0.93). This yielded a nonsignificant relative reduction in mortality of 10% in the screening group. The difference in the reduction in mortality between the current and historical groups that could be attributed to screening alone was 2.4 deaths per 100,000 person-years, or a third of the total reduction of 7.2 deaths. The authors concluded that the implementation of a screening mammography program explained only one-third of the reduction in breast cancer mortality.

Commentary

Whether routine screening mammography results in a clinically important reduction in the risk of breast cancer mortality remains a hotly contested issue. In November 2009, the U.S. Preventive Services Task Force (USPSTF) released revised recommendations for breast cancer screening.1 The USPSTF recommended against routine screening mammography in women ages 40-49 years and concluded that the risk of harm attributable to screening exceeds the potential benefit for low-risk women. Mammography was recommended for women ages 50-74 years, but only every two years, and the USPSTF concluded that the evidence of additional benefits and harms of screening mammography in women 75 years or older was inconclusive. The task force also found the evidence insufficient to recommend clinical breast examination in women age 40 or older that undergo mammography and determined that teaching breast self-examination (BSE) is not longer recommended.

I reviewed these guidelines and background information including positions from ACOG and the American Cancer Society (both recommend annual mammograms starting at age 40) in the January 2010 issue of OB/GYN Clinical Alert.2 The primary benefit of screening at an earlier age is a reduction in mortality and the risk is unnecessary interventions; annual mammograms starting at age 40 instead of age 50 and continued to age 69 will prevent one additional cancer death (8.3 vs 7.3) for every 1,000 women screened at the expense of 63 unnecessary biopsies. In other words, 10 additional years of mammogram screening yields a 6% chance of getting a biopsy but only a 0.1% chance of avoiding cancer mortality. If women are screened every other year starting at age 40 until age 69, there will be 70 fewer biopsies per 1000 women, but two additional women/1,000 will die from breast cancer.3

While we should not dismiss the burden of screening, most of us consider death an even less desirable outcome. However, if the observed reduction in breast cancer mortality is not associated with mammography screening, but is instead due to other factors, mammogram screening should be abandoned. The recent publication of data from the Norwegian Breast Cancer Screening Program put this issue back in the public eye again, so prepare for more calls from patients.

To determine whether the results of the Norwegian study provide guidance to U.S. clinicians, let's look at the screening program itself. Norway has a population of 4.8 million and a public health care system. Patients generally receive treatment in their county of residence, and there is no private primary care (e.g., mammograms) for breast cancer. The Breast Cancer Screening Program (BCSP) began as a pilot project in four of the 19 Norwegian counties in 1996, but it was expanded to the remaining 15 counties over the next nine years, and it has offered screening mammography to all women between the ages of 50 and 69 since 2005.

Women receive an invitation by mail to participate in screening, and 77% of all women who are invited participate in the program and obtain a standard two-view film mammogram. Breast cancer specialty services are centralized for all residents within each county; establishing these specialty teams was a prerequisite to participation in the BCSP.

In an attempt to avoid confounding due to improvements in treatment and heightened awareness due to the establishment of the breast specialty services, the authors compared death rates in counties with and without screening before and after the introduction of the BCSP. They first compared women in the nonscreening group with their historical counterparts to determine the temporal change in mortality that was not attributable to the introduction of the screening program (reflecting improved treatment and earlier clinical diagnosis) and then compared women in the screening group with their historical counterparts to determine the change in mortality after implementation of the screening program (attributable to both the screening program as well as temporal trends in mortality that were unrelated to the screening program). They then calculated the reduction in mortality that was related to the screening program as the difference between the rate ratio for death among women in the screening group as compared with their historical counterparts, and the rate ratio for death among women in the nonscreening group as compared with their historical counterparts.

Simple enough for a statistician, but what does this mean to patients and clinicians in the Unites States where screening is much more widely established?

The overall crude death rate from breast cancer in U.S. women ages 50-65 in 2005 was about 21.4/100,000.4 This rate is comparable to the rate seen among nonscreened women of the same age in Norway (21.2/100,000). The prevalence of mammography screening in the United States among women ages 50-64 in 2005 varied from 50% in poor women to 77% among well off women,5 while in Norway this was more than 70% for everyone. As the proportion of women screened with mammography has increased, the death rate from breast cancer in the United States has declined 3.2% in women younger than age 50 and 2% in women older than age 50.4 This decline in breast cancer mortality has been attributed to both improvements in breast cancer treatment and early detection, and it is difficult to tease out these effects.

The Norwegian paper suggests that mammography results in a nonsignificant reduction of only 2.4 deaths among 100,000 screened women ages 50-69. Most of the reduction in mortality was attributed to better care once cancer is diagnosed. Adding weight to the argument are data that demonstrated a similar reduction in mortality among older and younger age groups that did not undergo screening mammography that was attributable entirely to better treatment.

Before abandoning mammography, it is important to consider that we start screening earlier in the United States, and screen annually rather than every two years. Annual screening may be of particular benefit to younger women who are more likely to develop fast growing tumors.1 Data from U.S. studies do demonstrate a small but real reduction in mortality with annual screening. These reductions in mortality may only be one case per 1,000 women screened, but women are highly motivated to avoid that statistic.

A logical and rational distribution of health care resources requires us not to hold on to any sacred cows. However, more data will be needed to determine if routine mammography is ready to be sacrificed. In my opinion, it is premature to abandon our current screening practices on the basis of the data in the Kalager paper. At the same time, we should continue to evaluate this important topic as more data become available.

References

  1. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2009;151: 716-726.
  2. Jensen JT. USPSTF Mammography Recommendations: Seeing through the screen. OB/GYN Clin Alert 2010;26:65-68.
  3. Mandelblatt JS, et al. Effects of mammography screening under different screening schedules: Model estimates of potential benefits and harms. Ann Intern Med 2009;151:738-747.
  4. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999-2005 Incidence and Mortality Web-based Report. Atlanta: Centers for Disease Control and Prevention and National Cancer Institute; 2009. Available at: www.cdc.gov/uscs.
  5. American Cancer Society. Breast Cancer Facts & Figures 2009-2010. Atlanta: American Cancer Society; 2009.