Mammography: Does Early Detection Matter?

Abstract & Commentary

By Jeffrey T. Jensen, MD, MPH, Leon Speroff Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland. Dr. Jensen is a consultant for Bayer Healthcare and Population Council; is a speaker for Bayer Healthcare and Merck; receives research support from Agile Pharmaceuticals, Bayer Healthcare, HRA Pharma, Merck, and Population Council; and is on the advisory boards of Bayer Healthcare, Merck, HRA Pharma, and Agile Pharmaceuticals.

This article originally appeared in the January 2013 issue of OB/GYN Clinical Alert.

Synopsis: Although widespread screening mammography has greatly increased the diagnosis of early breast cancer, it has had only a marginal effect on the diagnosis of late-stage tumors and breast cancer mortality.

Source: Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 2012;367:1998-2005.

To evaluate the effectiveness of mammography as a screening test, the authors used the Surveillance, Epidemiology, and End Results (SEER) database to examine trends from 1976 through 2008 in the incidence of earlystage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older 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, from 112 to 234 cases per 100,000 women: an absolute increase of 122 additional breast cancer cases per 100,000 women. At the same time, the rate at which women presented with late-stage cancer decreased by only 8%, from 102 to 94 cases per 100,000 women: an absolute decrease of just 8 cases per 100,000 women. The authors concluded that with the assumption of a constant underlying disease burden (e.g., no change in the biology or virulence of breast cancer), only 8 of the 122 additional early-stage cancers diagnosed by mammography would have been expected to progress to advanced disease. In other words, according to these data, most of the tumors detected by screening would never have led to clinical symptoms or required treatment of any kind. After adjusting the numbers for the transient excess cancer incidence associated with hormone-replacement therapy and for trends in the incidence of breast cancer among women younger than 40 years of age, the authors estimated that routine screening mammography has led to the “overdiagnosis” and treatment of breast cancer in 1.3 million U.S. women over 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 breast cancers diagnosed.

Commentary

Many American women and their doctors sat down on Thanksgiving Day confronted with new information questioning whether screening mammography is one of the things for which they should be thankful. During the last 30 years, considerable effort has led to broad acceptance of routine screening mammography as an essential health care service, with mandated coverage now the law of the land. Effective screening programs are widely supported because breast cancer is a pernicious and indiscriminate killer that takes our mothers, sisters, daughters, wives, and friends. With few options for effective treatment of advanced breast cancer, early detection and treatment has understandably been the focus of attention for many advocacy groups. However, the goal of screening is the detection of life-threatening disease at an earlier, more curable stage. Therefore, the effectiveness of cancer-screening programs should be judged not just by the increase in the incidence of cancer detected at an early stage, but also by a decrease in the incidence of cancer presenting at a late stage and a reduction in overall mortality.

Bleyer and Welch used the SEER database to investigate the hypothesis that routine screening mammography starting at age 40 is an effective screening strategy. Their conclusions that yearly tests lead to a large increase in diagnosis of early tumors but do not reduce the diagnosis of advanced tumors or greatly impact breast cancer mortality support the earlier recommendations against annual routine screening mammography starting at age 40 published by the U.S. Preventive Health Task Force (USPHTF) in 2009.1

Although screening mammography substantially increases the number of cases of early-stage breast cancer detected, unlike cervical cancer screening, this has only marginally reduced the rate at which women present with advanced cancer. This leads to two questions: 1) Does the benefit of routine screening mammography outweigh the potential for harm? and 2) Should the health care dollars invested in screening be redirected instead to research and treatment of clinically important tumors?

The answer to the first question is the clinical point that you will need to address with each women age 40 or older in the office. It is important to acknowledge that we do not have a highly sensitive and specific method of screening for advanced breast cancer. Although we recognize that mammography is not perfect, the relief most women experience with a negative test is considerable. Unfortunately, an uncomfortably common result is a “positive” screening examination and the sequence of events that stems from this. Although routine annual mammograms starting at age 40 instead of age 50 and continued to age 69 do reduce breast cancer mortality, the overall effect is small. This strategy will prevent one additional cancer death (8.3 vs 7.3) for every 1000 women screened at the expense of 63 more “unnecessary” biopsies.2 You and your patient need to decide if a 6% chance of getting a biopsy is worth the 0.1% chance of avoiding cancer mortality associated with annual screening at age 40 (recommended by ACOG and the American Cancer Society) or age 50 (recommended by the USPHTF). There will be 70 fewer biopsies in 1000 women age 40-69 who get mammograms every other year compared to annually, but two additional women will die from breast cancer.2 So if you are willing to risk more intervention, mammography does reduce the risk of breast cancer mortality, although the effect is small. Many women gladly will accept the high burden of a breast biopsy to reduce the chance of breast cancer death. But this is personal and should be discussed in real terms with each patient.

On the flip side, the high “false-positive” rate and anxiety during the work-up of a positive screen should not be underestimated. Furthermore, the data from Bleyer and Welch suggest that the majority of early breast cancers detected may never become clinically important. Their results suggest that in 2008 more than 70,000 women (accounting for one-third of all breast cancer diagnoses in women ≥ 40) were “overdiagnosied” (e.g., the cancer diagnosed would never have progressed to clinically important disease). If true, this represents a substantial harm of even most “true-positive” screening mammogram results.

The second question has enormous public health impact in our role as advocates for all women, not just the patient in front of us. Considerable evidence suggests that the reduction of breast cancer mortality observed over the last 30 years is due more to effective treatment than to early detection.3 Bleyer and Welch concluded that the impact of early detection on decreasing numbers of deaths must be small because the absolute reduction in deaths (20 deaths per 100,000 women) observed during the 30-year study period is larger than the absolute reduction in the number of cases of late-stage cancer (eight cases per 100,000 women). Furthermore, they point out that this small reduction in cases of late-stage cancer is confined to regional (largely node-positive) metastatic disease. In other words, screening mammography did not influence the number of women presenting with advanced metastatic disease.

According to the 2010 census, there are more than 52 million women aged 40-65, and the average cost of a mammogram is $266.4 The math tells us that a universal annual screening mammography program will cost almost $14 billion, and this 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. Imagine a $14 billion dollar investment in research into better diagnostics and treatment for truly life-threatening breast cancers.

Like many OB/GYNs, I spent a large proportion of my early years in practice performing colposcopy and treating early cervical dysplasia. Now we know that cervical cancer is caused by a virus, that screening intervals can be greatly reduced, and that most early lesions do not require treatment at all. I hope that we can see a similar shift in practice with respect to breast cancer screening and treatment in the near future. In the meantime, ACOG and the American Cancer Society still recommend annual screens at age 40. The evidence for annual exams does support a modest benefit to individual women at the expense of unnecessary follow-up and biopsies (and perhaps unnecessary treatment). I am beginning to shift away from a strong advocacy for routine mammography, but only when we agree to shift the resources to a better approach. Breast cancer is a horrible disease. We should all agree that more research is needed.

References

1. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716-726, W-236.

2. 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.

3. Esserman L, et al. Rethinking screening for breast cancer and prostate cancer. JAMA 2009;302:1685-1692.

4. Henderson LM, et al. Assessing health care use and cost consequences of a new screening modality: The case of digital mammography. Med Care 2012;50:1045-1052.