Annual mammography starting at age 40: More talk, less action?
National societies agree on the value of mammographic screening at age 50 through 69 (though the frequency is still debated), but there is no consensus about whether to screen at age 40 through 49, or age 70 and older. The US Preventive Services Task Force (USPSTF) recommends against routinely screening women age 40 through 49, while the American Academy of Family Physicians and the American College of Physicians recommend screening every 1 to 2 years for women in this age group. The American Cancer Society, the American Medical Association, the National Cancer Institute, the American College of Radiology, and the American Congress of Obstetricians and Gynecologists recommend yearly mammography starting at age 40.1
Besides female sex, the major risk factor for breast cancer is increasing age. Thus, women in their 40s are at significantly lower risk of breast cancer than those in their 50s. As emerging evidence focuses on the potential harms and benefits from screening, we must question the practice of annual screening starting at age 40.
DOES MAMMOGRAPHIC SCREENING SAVE LIVES?
The main goal of screening for any type of cancer is to reduce the death rate. A 2014 meta-analysis of randomized controlled trials found a 15% to 20% relative decrease in the breast cancer mortality rate with screening mammography, approximately 15% for women in their 40s and 32% for women in their 60s.2 Since the prevalence of breast cancer is lower in younger women, many more women in their 40s must be screened to prevent one breast cancer death. For women age 60 to 69, 377 must be screened to prevent one breast cancer death, whereas for women age 39 to 49 the number is 1,904.3
Whether screening for breast cancer reduces the death rate has been questioned following the 2014 publication of 25-year follow-up data from the Canadian National Breast Screening Study.4 This randomized controlled trial of screening mammography and clinical breast examination, launched in 1980, involved 89,835 women and 5 years of screening. Women age 40 to 49 were randomly assigned to undergo either five annual mammographic screenings and annual clinical breast examinations or no mammography and a single clinical breast examination, followed by usual care in the community. Those age 50 to 59 received annual clinical breast examinations and were randomized to either mammography or no mammography.
During 25 years of follow-up, 3,250 women in the mammography group and 3,133 in the control group were diagnosed with breast cancer, and 500 and 505, respectively, died of breast cancer. No difference in mortality rate was found between the mammography and control groups (hazard ratio 0.99, 95% confidence interval 0.88–1.12), and the findings in both age cohorts were similar.4
Criticisms of this study include that it was performed using outdated imaging technology, and that a significant proportion of the control group also received mammography, although it is also possible that the mortality benefit from mammographic screening alone may not be as high as once predicted.
Reduction in breast cancer mortality is likely from a combination of screening mammography and better treatment. The number of women presenting with late-stage cancers has decreased in the past 3 decades, but only slightly; and most of the decrease has been in regional, node-positive disease, a stage that can now often be treated successfully (the expected 5-year survival rate is 85% in women age 40 or older).5 For women with estrogen receptor-positive tumors, the combination of hormonal therapy and adjuvant chemotherapy has reduced the death rate by half.6
It has been 50 years since a large randomized controlled trial of mammographic screening has been done in the United States. Thus, further study is needed to understand whether screening is less valuable now that better treatments are available.
DOES MAMMOGRAPHIC SCREENING REDUCE LATE-STAGE CANCERS?
To be effective, screening must detect disease at an earlier, more curable stage. Although screening mammography has substantially increased the number of early-stage breast cancers detected, it has only marginally decreased the rate of diagnosis of late-stage cancers.5
The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data5 show that between 1976 and 2008 screening mammography was associated with a doubling in early-stage breast cancer cases detected (from 112 to 234 cases per 100,000 women per year, an absolute increase of 122 cases per 100,000 per year). In contrast, late-stage cancer diagnoses decreased by 8% (from 102 to 94 cases per 100,000 women per year, or an absolute decrease of 8 per 100,000 women per year). Assuming a constant underlying disease burden, only 8 of the 122 early-stage cancers diagnosed would be expected to progress to advanced disease, suggesting that the rest would have never harmed these women—ie, they were overdiagnosed. The authors estimated that in 2008, breast cancer was overdiagnosed in more than 70,000 women, accounting for 31% of all diagnosed breast cancers.5
HARMS OF OVERDIAGNOSIS
Based on SEER data, Bleyer and Welch5 estimated that more than 1 million US women may have been overdiagnosed with breast cancer in the past 3 decades. Many women in this situation subsequently undergo surgery, radiation therapy, hormonal therapy, chemotherapy, or a combination of these for a cancer that may never become clinically significant. Until we can differentiate deadly from indolent cancers, highly sensitive screening tests will increase the risk of overtreatment.
Breast cancer has increased in incidence since the 1990s, mostly from the detection of more early-stage cancer or ductal carcinoma in situ (DCIS). Rare before widespread screening, DCIS now accounts for 20% to 30% of all breast cancer diagnoses.6,7 However, DCIS is not always a precursor to invasive cancer: untreated, it progresses to invasive disease in half of cases or fewer. Because DCIS is usually diagnosed only with mammography, its incidence has been steadily on the rise since screening became widespread.1
Welch and Passow6 reviewed the available evidence and attempted to provide a range of estimates for three outcomes important to the mammography decision: breast cancer deaths avoided, false alarms, and overdiagnosis. For every 1,000 US women screened yearly for a decade starting at age 50, an estimated 0.3 to 3.2 avoided breast cancer death, 490 to 670 had at least one false alarm, and 3 to 14 were overdiagnosed and treated needlessly.
Esserman et al7 calculated that in women age 50 to 70, prevention of one breast cancer death would require that 838 women be screened for 6 years, leading to 5,866 screening visits, 535 recalls, 90 biopsies, and 24 cancers treated (18 invasive, 6 DCIS).
