Annual Mammography Screening: The Debate Continues
Abstract & Commentary
By Jeffrey T. Jensen, MD, MPH, Editor
Synopsis: Although annual screening mammography did increase the detection rate of non-palpable tumors, it did not reduce mortality from breast cancer over 25 years of follow-up.
Source: Miller AB, et al. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial. BMJ 2014;348:g366.
In 1980, the canadian national breast screening study, a random-ized controlled trial of screening mammography and physical examination of breasts in women aged 40-59, was initiated in Canada. Screening mammography was not routinely available in Canada at that time. However, diagnostic evaluation of a breast mass and surgical and adjuvant therapy for breast cancer was freely available to all women. The study was designed to evaluate the benefit of screening women aged 40-49 with mammography compared with usual care (no active screening) and to determine the risk benefit of adding annual mammography to annual breast physical examination in women aged 50-59. The study involved a 5-year period of screening that ended in 1988 followed by a follow-up period of 6-25 years. This publication reports the results of breast cancer mortality.
A total of 89,835 women ages 40-59 were randomized. During the 5-year screening period, invasive breast cancers were diagnosed in 1.5% (666/44,925) of women in the mammography arm and 1.2% (524/44,910) in the control arm. Of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25-year follow-up period (overall hazard ratio [HR] for death from breast cancer diagnosed during the screening period, 1.05; 95% confidence interval [CI], 0.85-1.30). There was no difference in the findings for women aged 40-49 (HR, 1.09; CI, 0.80-1.49) who received no additional screening and those 50-59 (HR, 1.02; CI, 0.77-1.36) who received annual clinical breast examinations.
Over the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer. There was no difference in the cumulative mortality from breast cancer between the groups (mammography arm, 500 deaths; control arm, 505 deaths; HR, 0.99; CI, 0.88-1.12). Most (68%) of the tumors diagnosed by mammography were palpable (mean size 2.10 cm) at the time of the exam. During the screening interval, 142 excess tumors were diagnosed in the mammogram cohort; over 15 years of follow-up, the number of excess tumors became constant at 106.
The authors conclude that annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Furthermore, women in screening mammography programs are at risk for over-diagnosis of serious breast cancer. The 22% (106/484) of mammography screen-detected invasive breast cancers did not contribute to a reduction of breast cancer mortality. For every 424 women in the study who received mammography screening, one received an over-diagnosis of breast cancer.
Physical examination has gone out of vogue, and imaging is stressed as the gold standard for almost all conditions. Ask a group of students or residents to work up almost any patient complaint and it won't be long before an imaging test is suggested. The dogma that imaging can only help is widely accepted and we invest billions of dollars in imaging studies. But is the tide turning for mammography? The cracks that have appeared in the ceiling that protect mammography screening programs appear to be of little consequence compared to this recent report that shakes the very foundation that justifies routine imaging.
Screening mammography has received broad acceptance from clinicians, politicians, and the public. This has continued despite evidence that mammography may put women at risk for an increase in intervention due to a false-positive study. Although data from studies in the United States suggests that starting annual mammograms at age 40 instead of age 50 may prevent one additional cancer death (8.3 vs 7.3) for every 1000 women screened, this comes at a cost of 63 unnecessary biopsies.1 The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening mammography in women age 40-49 years, concluding that the risk of harm attributable to screening exceeds the potential benefit for low-risk women.2 Mammography for women age 50-74 years is recommended, but only every 2 years, and the USPSTF concluded that the evidence of additional benefits and harms of screening mammography in women 75 years or older was inconclusive. These recommendations have not been adopted by the American College of Obstetricians and Gynecologists or the American Cancer Society.
Further erosion of the enthusiasm for screening mammography came from the landmark paper from Bleyer et al published in the New England Journal of Medicine in 2012.3 The authors used the Surveillance, Epidemiology, and End Results database to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women ≥ 40 years of age in the United States. During this time interval, screening mammography was associated with a doubling in the number of cases of early-stage breast cancer detected each year, but the rate at which women presented with late-stage cancer decreased by only 8%. After adjusting the numbers for potential confounders, the authors estimated that routine screening mammography led to the "overdiagnosis" and treatment of breast cancer in 1.3 million U.S. women during the past 30 years. They estimated that in 2008 alone, breast cancer was overdiagnosed in more than 70,000 women — just under one-third of all women in whom breast cancer was diagnosed.
The new results from this well-designed and conducted randomized trial done in Canada provide further evidence that treatment programs for breast cancer are more important than screening programs. Surgical and adjunctive breast cancer treatment was available as part of the Canadian Health Care system to all women. Although not directly evaluated in this study, a good clinical exam may be important after all, and at least as good as mammography. A clinic visit costs about the same as a mammogram (average cost of a mammogram is $266.40), and I believe that we accomplish a lot of other good health interventions and education during these visits. It is time to lower health care costs and reclaim our patients (and the revenue that comes with this).
According to the 2010 U.S. census, there are more than 52 million women aged 40-65. The cost of a universal program for screening mammography for this group is almost $14 billion annually. This cost does not include the cost of follow-up imaging studies and biopsy procedures for "false-positive" studies or for the treatment cost of "overdiagnosed" tumors. Add to this the personal economic cost to individual women due to time spent in screening, follow-up, and treatment, and the emotional stress and suffering by women with false-positive studies. Imagine the impact of an investment of an additional $14 billion into research for better diagnostics and treatment for truly life-threatening breast cancers.
In my opinion, the current evidence does not support the recommendation for screening mammography in women 40-59. Just as with pap tests, we are learning to do better with less screening, but it will not be easy to communicate this message to patients. Don't expect to see government agencies or major insurers adopting a no-screen recommendation, at least not in an election year. But you should expect to discuss these new and widely reported results with patients before ordering a screening mammogram.
- Mandelblatt JS, Silliman R. Hanging in the balance: Making decisions about the benefits and harms of breast cancer screening among the oldest old without a safety net of scientific evidence. J Clin Oncol 2009;27:487-490.
- US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716-726, W-236.
- Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 2012;367:1998-2005.