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 reports he is a consultant for and receives grant/research support from Bayer, Merck, ContraMed, and FHI360; receives grant/research support from Abbvie, HRA Pharma, Medicines 360, and CONRAD; and is a consultant for the Population Council.
Compared to women who undergo breast cancer screening with mammography alone, those receiving MRI exams experience a two- to fivefold increased rate of core and surgical biopsy. However, the biopsies have a lower cancer yield rate than mammography alone.
Buist DM, Abraham L, Lee CI, et al. Breast biopsy intensity and findings following breast cancer screening in women with and without a personal history of breast cancer. JAMA Intern Med 2018; Feb. 12. doi: 10.1001/jamainternmed.2017.8549. [Epub ahead of print].
Women’s health providers must help patients make decisions on preventive health care, including cancer screening. An improved understanding of the biology of cervical cancer has allowed us to better focus our screening efforts on molecular testing, and women have benefited from the improved precision and reduction in screening interval. However, no such progress has occurred with respect to breast cancer screening. Since 2015, many states have passed laws requiring notifying women with dense breasts of limitations of mammography. This has greatly increased the use of supplemental testing, such as ultrasound and magnetic resonance imaging (MRI). However, few studies have evaluated the population benefits and risks of additional screening.
To better inform this debate, Buist and colleagues performed an observational cohort study of six Breast Cancer Surveillance Consortium registries (Carolina Mammography Registry [North Carolina], Kaiser Permanente Washington Registry [Washington State], Metro Chicago Breast Cancer Registry, New Hampshire Mammography Network, San Francisco Mammography Registry, and Vermont Breast Cancer Surveillance System) that included a population-based sample of 812,164 women undergoing screening between 2003 through 2013. The primary objective of the study was to compare mammography screening alone to MRI (with or without mammography) and evaluate biopsy rates and yield in the 90 days following screening. The authors evaluated biopsy intensity (fine needle aspiration) and biopsy result within biopsy intensity (benign, high-risk benign, ductal carcinoma in situ [DCIS], or invasive), adjusting for demographic and facility characteristics, and stratified results by screening episode type and personal history of breast cancer (PHBC).
Women in the population sample underwent a total of 2,048,994 breast screening episodes during the study period: 101,103 and 1,939,455 in women with and without PHBC, respectively. This sample included 8,436 women who received an MRI (3,763 with PHBC, 4,673 without PHBC).
Compared to mammography alone (23.6; 95% confidence interval [CI], 22.4-24.8), age-adjusted core and surgical biopsy rates (per 1,000 episodes) doubled following MRI exams among women with PHBC (57.1; 95% CI, 50.3-65.1) and increased more than fivefold in women without PHBC (from 14.9 [95% CI, 14.7-15.0] to 84.7 [95% CI, 75.9-94.9]). However, the increased intensity of screening did not increase the biopsy yield in high- or average-risk women. The DCIS and invasive biopsy yield actually was significantly higher following mammography (404.6; 95% CI, 381.2-428.8) compared with MRI (267.6; 95% CI, 208.0-337.8) in women with a PHBC, and nonsignificantly higher, but in the same direction, in women without PHBC (mammography, 279.3 [95% CI, 274.2-284.4]; MRI, 214.6, [95% CI, 158.7-280.8]). MRI did increase the detection of high-risk benign lesions regardless of PHBC. The higher biopsy rates and lower cancer yield following MRI were not explained by increasing age or higher five-year breast cancer risk.
Overall, these results add to a growing literature on the potential harms of breast cancer screening. Based on the absence of benefit, the authors suggested that clinicians counsel women that, when compared to mammography alone, undergoing a screening MRI increases their risk of undergoing an unnecessary core or surgical breast biopsy.
COMMENTARY
I am bothered by the trend in medicine to use additional imaging as the solution to diagnostic uncertainty. When I teach students, I remind them that imaging is not treatment. Prior to ordering any test, the clinician must consider the expected results and actions. Great clinicians understand the risks and limitations of testing, and communicate pros and cons to patients in understandable language. The highly emotional subject of breast cancer screening requires clear discussion of potential harms as well as benefits.
Last year, the U.S. Preventive Services Task Force published updated guidelines for breast cancer screening,1 recommending biennial screening mammography for all women aged 50 to 74 years. For women younger than 50 years of age, the recommendation for screening mammography received a “C” grade (moderate certainty that the net benefit of screening, while positive, is small). As we have discussed previously in OB/GYN Clinical Alert, the decision to undergo screening more frequently than every other year or before age 50 requires an evaluation of potential benefits and harms.2 Harms include the risk of undergoing an invasive procedure that does not result in an improved outcome following a supplemental screening tests. In a recent review, Nelson et al considered potential harms to include both false-positive and false-negative imaging results, “overdiagnosis,” anxiety and other psychological responses, pain during procedures, and radiation exposure.3 They defined overdiagnosis as a diagnosis of DCIS or invasive breast cancer considered unlikely to become clinically important in the women during their lifetime in the absence of screening. Keep in mind that there is no consensus definition of overdiagnosis, and it is difficult to determine the significance of a breast cancer diagnosis to an individual woman. Our goal is not to increase the detection of breast cancer, but to reduce breast cancer mortality, so all screening tests must be evaluated by this metric.
The current study by Buist et al adds to our understanding of the effect of supplemental MRI screening for breast cancer detection. Women who underwent an MRI were more likely to undergo an invasive biopsy, but these biopsies were less likely to yield a diagnosis of DCIS or invasive cancer. Low-risk women without a PHBC had the lowest biopsy yields. We would term these “false-positive” screening tests. Women receiving negative results generally feel relieved, but do they benefit from additional screening?
Researchers have estimated that with current breast cancer treatment protocols, 3,448 women need to be screened to prevent one breast cancer death.4 For each breast cancer death prevented, three women receive an overdiagnosis of a nonfatal cancer and undergo surgery (including mastectomy) and/or medical treatments.5 In other words, as we increase breast cancer screening, we tend to increase overdiagnosis, magnifying screening costs without affecting the risk of breast cancer death.
Every medical school, including my own, wants to market itself as a “Cancer Center.” Battling cancer should be a major goal for medical science. Unfortunately, I see much of the effort centered on new diagnostic modalities that are not treatment. We seduce the public with the prospect of advanced imaging, robotics, and personalized medicine. Not surprisingly, they expect miracles. As clinicians, we need to help our patients negotiate the false (or premature) claims. Cautioning women with dense breasts that additional screening with MRI will increase their risk of undergoing an invasive biopsy procedure, but not significantly decrease their risk of breast cancer mortality, requires time and effort, but is our responsibility.
REFERENCES
- Siu AL, U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2016;164:279-296.
- Jensen JT. 2016 USPSTF Update: Recommendations for and effectiveness of screening mammography. OB/GYN Clinical Alert 2016;32:81-83.
- Nelson HD, Pappas M, Cantor A, et al. Harms of breast cancer screening: Systematic review to update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med 2016;164:256-267.
- Autier P. Efficient treatments reduce the cost-efficiency of breast cancer screening. Ann Intern Med 2016;164:297-298.
- Marmot M, Independent UK Panel on Breast Cancer Screening, Altman G, et al. Independent UK Panel on Breast Cancer Screening replies to Michael Baum. BMJ 2013;346:f873.
