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 HRA Pharma, Bayer Healthcare, Merck, Agile Pharm, Population Council, AbbVie, Evofem, and ContraMed; and is a consultant for Teva Pharmaceuticals and Microchips.

SYNOPSIS: A cost-effectiveness model found that supplemental ultrasound screening after a negative mammogram for women with dense breasts substantially increases costs without yielding significant benefit.

SOURCE: Sprague BL, et al. Benefits, harms, and cost-effectiveness of supplemental ultrasonography screening for women with dense breasts. Ann Intern Med 2015;162:157-166.

Since mammographic breast density can affect the performance of screening mammography, and is also an independent risk factor for breast cancer, ultrasound is commonly recommended as a secondary screening test. Since little is known about the effectiveness of ultrasound as a secondary screen, the authors used data from the Surveillance, Epidemiology, and End Results (SEER) Program and Breast Cancer Surveillance Consortium to evaluate the benefits, harms, and cost-effectiveness of supplemental ultrasonography screening for women with dense breasts. Three independent Cancer Intervention and Surveillance Modeling Network breast cancer models were used. The models simulated life histories of women who were at risk for breast cancer, had screening, were treated for breast cancer diagnosed by screening or clinical detection, and were at risk for dying of breast cancer and other causes. Although the models had independent approaches and structures, they approximately replicated U.S. breast cancer incidence and mortality trends and used common inputs, including incidence in the absence of screening, mammography performance, treatment effectiveness, and competing causes of death. The cost analyses assumed a federal payer perspective. The performance of screening ultrasound was assumed to be 55% sensitive and 94% specific. The cost of ultrasound was conservatively estimated at $100. Models estimated breast cancer mortality rates, life-years, quality adjusted life-years (QALYs), false-positive examination results, and costs across the lifetimes of each simulated woman beginning at age 40 years. Within-model cost-effectiveness ratios were calculated for mammography-alone vs mammography with follow-up ultrasound.

Results of these analyses showed that for women aged 50 to 74 years with heterogeneously or extremely dense breasts, supplemental ultrasonography screening after a negative mammogram result averted 0.36 additional breast cancer deaths (range across models, 0.14 to 0.75), gained 1.7 QALYs (range, 0.9 to 4.7), and resulted in 354 biopsy recommendations for false-positive ultrasonography result (range, 345 to 421) per 1000 women with dense breasts compared with biennial screening by mammography alone. The cost-effectiveness ratio was $325,000 (range, $112,000 to $766,000) per QALY gained. Restricting the analyses to only those women with extremely dense breasts reduced the cost to $246,000 (range, $74,000 to $535,000) per QALY gained. The authors performed sensitivity analyses that demonstrated that the conclusions were not sensitive to ultrasonography performance characteristics, screening frequency (annual vs biennial), or starting age.

The authors concluded that supplemental ultrasonography screening for women with dense breasts would substantially increase costs while producing relatively small benefits.


Why has women’s health care become such a topic of legislative interference? Although we have become used to legislation affecting reproductive health issues, a number of advocacy groups have lobbied to increase access to medical procedures. One area of specific interest has been health care screening services for women, in particular breast cancer screening. I am a strong supporter of universal health care access and public insurance. However, we need to consider carefully the menu of services offered since resources will always be limited. To provide the greatest good to the greatest number, we need to rely on careful evidence of comparative effectiveness. We all contribute to health care costs and value as providers and consumers. There is no such thing as someone else’s money. Through taxes, our health insurance premiums, and the cost of services we purchase, we collectively pay the ever-increasing cost of health care. Therefore, we need to make careful evidence-based choices.

Consider family planning services. For every dollar spent on contraceptive services (including the expensive LARC methods), we save $4-5 on other direct health care expenditures.1 That is the major reason that contraceptive care features prominently in the Affordable Care Act. Yet despite the evidence, legislative and judicial forces have conspired to weaken the intent of universal contraceptive coverage. We need to fight back on this one.

Interference by advocacy groups in health care is often based more on emotional hot button issues rather than fact. Consider the case for breast cancer screening. One source of concern about mammography is that the sensitivity is affected by breast density. This has led advocates to lobby for laws that require notification of patients with dense breasts about this concern along with a recommendation for a screening ultrasound. These laws have passed in 24 states as of July 2015, with 9 more states considering the legislation ( But is this good for women?

Until the study by Sprague et al, there has been no formal evaluation of the practice of screening ultrasound in this population. We do know that the U.S. Preventive Services Task Force and others have issued evidence-based guidelines for screening practices that question the frequency of mammogram screening.2,3 I have previously reported that the results from several studies4-6 suggest that screening mammography also results in widespread overdiagnosis of breast cancer. Overdiagnosis is a true positive result of screening that fails to result in a net benefit to the patient. In the case of breast cancer overdiagnosis, the possibility of harm is real when one considers mastectomy, chemotherapy, and out-of-pocket treatment costs. This is in addition to the false-positive screens that result in additional unnecessary worry and follow-up interventions.7

The argument of advocates (and many radiologists) is that since dense breasts are hard to image, follow-up imaging will improve sensitivity, detect more cancers, and save lives. However, the evidence previously reviewed strongly suggests that overdiagnosis of breast cancer may in fact be harming women. Therefore, it makes sense to critically evaluate the result of adding ultrasound to the screening paradigm.

Sprague et al used strong methodology to model the effects of adding a screening ultrasound after a normal mammogram test in women with dense breasts. They found consistent results using three separate models, and the conclusions were robust and unchanged in a sensitivity analysis. The key conclusion of minimal benefit and high cost is best summarized by looking at the effect on women aged 50-74 with extremely dense breasts. In this group, use of supplemental screening ultrasonography averted 0.30 additional breast cancer deaths (range, 0.14 to 0.75) and produced 1.1 additional QALYs per 1000 women. This median 1.1 QALYs gained per 1000 women is equal to only 9.6 hours per woman! And, this marginal gain comes at a cost of 189 biopsies recommended after a false-positive ultrasonography result and a cost of $287,000 for the 1000 women (or $287 per woman). If we expand this to include women with heterogeneously dense breasts, only an additional 0.06 additional breast cancer deaths are averted, but the total cost increases to $560,000 per 1000 women. Consider too that this cost estimate is likely low, as a federal payer perspective was used, and the estimate for breast ultrasound was a conservative $100.

As clinicians, we have to think of what is best for the patient in front of us, and we are taught not to think of dollars. But could this money be better spent on improved screening approaches? I am not convinced that imaging is the answer. Remember when diagnosis of fetal aneuploidy through a maternal blood test was a pipe dream? More research is needed. Also, we need to consider the emotional impact of false-positive screening results, and the impact of true positive tests that may in fact be overdiagnosis. To be fair, many women are willing to accept the risks of screening for the potential benefit. Our job is to provide a good discussion of the trade-off.


  1. Sonfield A. Contraceptive coverage at the U.S. Supreme Court: Countering the rhetoric with evidence. Guttmacher Policy Review 2014;17:1-8.
  2. Nelson HD, et al. Screening for Breast Cancer: Systematic Evidence Review Update for the US Preventive Services Task Force. U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. Rockville, MD; 2009.
  3. Nelson HD, et al. Risk factors for breast cancer for women aged 40 to 49 years: A systematic review and meta-analysis. Ann Intern Med 2012;156:635-648.
  4. Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Eng J Med 2012;367:1998-2005.
  5. 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.
  6. Harding C, et al. Breast cancer screening, incidence, and mortality across us counties. JAMA Intern Med 2015;175:1483-1489.
  7. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:I44. doi: 10.7326/0003-4819-151-10-200911170-00002.