For the past 30 years, mammography screening has been one of the most contentious issues in medicine. Controversy has generally centered on the age at which to begin mammography screening (40 vs 50 years) and also, to a lesser extent, on the age at which it should stop. The recent American Cancer Society (ACS) guidelines—summarized in this issue of The ASCO Post—are unlikely to quell such controversy.1
Two randomized trials have been specifically designed to assess the efficacy of mammography screening for women in their 40s: the Canadian National Breast Screening Study (CNBSS) I and the United Kingdom Age trial.2,3 In both trials, mammography screening for women in their 40s did not significantly reduce breast cancer mortality. Although other trials have included women in their 40s, those trials were not specifically designed to assess the efficacy of screening younger women.
Moreover, meta-analyses of the screening trials show that, among women who initiate mammography screening at age > 50 years, the mortality benefit is evident within 7 to 9 years, whereas for those who initiate screening in their 40s, the benefit takes longer to emerge.4 Many investigators have argued that the delayed benefit of screening younger women is simply attributable to screening beyond age 50 years. Thus, the ACS recommendations for screening women in their 40s do not seem consistent with the best evidence at hand.
Overdiagnosis Problem
The ACS guidelines do not specify the age at which mammography screening should stop. Yet of the nine randomized trials that have examined the efficacy of mammography screening, only the Swedish Two-County trial included women aged ≥ 70 years (women were aged 40–74 years at entry), but participation of this age group was low, and a subgroup analysis of four Swedish randomized trials found no mortality benefit for those aged 70 to 74 years at study entry.5 Without evidence of benefit, mammography screening in women aged ≥ 70 years is difficult to justify.
Indeed, older women are more vulnerable to the harms associated with mammography screening, particularly the vexing problem of overdiagnosis.6 Overdiagnosis refers to the diagnosis of a cancer that, in the absence of screening, would never have been detected during a patient’s lifetime. A population-based study has suggested that, in the United States, nearly one-third of all breast cancers would never have been diagnosed in the absence of screening.7
This substantial rate of overdiagnosis is partly due to the detection of ductal carcinoma in situ, which is rarely palpable and almost exclusively detected with screening mammography. Many cases of ductal carcinoma in situ would likely never progress to invasive cancer, and when they do progress, the process undoubtedly takes many years. Thus, ductal carcinoma in situ is unlikely to pose a threat to the life of an elderly woman, and its detection triggers treatments (surgery, radiotherapy, and endocrine therapy) that could have been avoided in the absence of screening mammography.
However, overdiagnosis is not simply attributable to the detection of ductal carcinoma in situ; it can also result from the detection of invasive cancers. Mammography screening preferentially detects indolent invasive cancers, whereas the more aggressive tumors are often detected in the intervals between screening sessions (length bias).6 Many indolent invasive cancers would pose no threat to the life of an elderly patient and might not be detected in the absence of mammography screening. As with ductal carcinoma in situ, detection of these cancers may trigger unnecessary treatments. Thus, overdiagnosis of breast cancer may expose elderly women to the risk of unnecessary treatment-related morbidity and mortality.
Clinical vs Self Breast Exam
The ACS recommendation against screening clinical breast examination is puzzling. Screening clinical breast examination is undertaken by trained health-care personnel and should be distinguished from screening breast self-examination, where women are instructed on self-breast examination.4
Two large randomized trials, undertaken in St. Petersburg, Russia, and Shanghai, China, have shown that screening breast self-examination does not reduce breast cancer mortality. However, screening clinical breast examination was incorporated into four of the nine mammography screening trials and showed promise.
In the Health Insurance Plan (HIP) trial of New York, women were randomized to mammography screening plus screening clinical breast examination vs usual care. In the screening arm of the trial, 67% of the cancers were detectable by clinical breast examination and only 33%, by mammography alone.
In the Edinburgh trial, 74% of the cancers in the screening group were detectable by clinical breast exam and only 26% by mammography alone.
In the CNBSS I, women aged 40 to 49 years at study entry were randomized to screening with mammography and clinical breast examination vs no screening. There was no reduction in mortality attributable to screening, but clinical breast examination detected 59% of the cancers in the study arm, with 32% detected by clinical breast examination alone and 27% detected by clinical breast examination and mammography.
In the CNBSS II, women aged 50 to 59 years at study entry were randomized to receive either screening with clinical breast examination and mammography (study group) vs clinical breast examination alone (control group). Whereas other trials have shown that mammography screening can effectively reduce breast cancer mortality in women older than 50 years, there was no difference in breast cancer mortality between the study and control groups of the CNBSS II trial. This finding might be interpreted to mean that mammography screening adds little benefit beyond that of screening clinical breast examination alone.
Mammography screening is likely to remain a contentious issue. As breast cancer treatments continue to improve, the benefit of screening in reducing breast cancer mortality is likely to decline.8 Moreover, the impact of screening on quality of life needs to be thoroughly considered. The harms associated with screening are not insignificant, and greater emphasis should be placed on reducing these adverse effects. ■
Disclosure: Dr. Jatoi reported no potential conflicts of interest.
References
1. Oeffinger KC, et al: Breast cancer screening for women at average risk. JAMA 314:1599-1614, 2015.
2. Miller AB, et al: Twenty five year follow-up for breast cancer incidence and mortality of the CNBSS. BMJ 348:g366, 2014.
3. Moss SM, et al: Effect of mammographic screening from age 40 years on breast cancer mortality in the UK Age trial at 17 years’ follow-up. Lancet Oncol 16:1123-1132, 2015.
4. Jatoi I, Anderson WF: Cancer screening. Curr Probl Surg 42:620-682, 2005.
5. Nyström L, et al: Long-term effects of mammography screening. Lancet 359:909-919, 2002.
6. Jatoi I, Miller AB: Breast cancer screening in elderly women. JAMA Surg. October 14, 2015 (early release online).
7. Bleyer A, Welch HG: Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 367:1998-2005, 2012.
8. Jatoi I: The impact of advances in treatment on the efficacy of mammography screening. Prev Med 53:103-104, 2011.
Dr. Jatoi is Dale H. Dorn Chair in Surgery, Professor and Chief, Division of Surgical Oncology and Endocrine Surgery, University of Texas Health Science Center, San Antonio.
