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For women who are shown to have dense breasts on mammography screening, the addition of ultrasound screening has little impact on outcome, increases harms, and drastically increases costs, researchers report.
The findings are published online on December 8 in the Annals of Internal Medicine.
Supplemental ultrasound screening for women with dense breasts has a high false-positive rate and substantially increases the number of unnecessary biopsies with little gain in quality-adjusted life years (QALYs), according to lead author Brian Sprague, PhD, codirector of the cancer control and population health sciences research program at the University of Vermont Cancer Center in Burlington, and colleagues.
Moreover, they add, the cost per QALY is more than $300,000.
The study is particularly relevant because national legislation is currently being considered that would make it mandatory to notify women of their breast density and discuss supplementary screening options. Similar legislation has been introduced in at least 19 states.
These notification laws have been a subject of debate for several years, as reported byMedscape Medical News, with experts questioning whether the laws are running ahead of the science on breast screening. Despite this, the introduction of such laws in individual states, including California, has continued apace.
Dr Sprague was involved in a previous study that found that 43.3% of women 40 to 74 years of age have dense breast tissue, which shows more glandular and connective tissue than fat on mammography (J Natl Cancer Inst. 2014;106[10]:dju255). This equates to 27.6 million women, 12.3 million of whom are 40 to 49 years of age.
"We know mammography does not perform as well for women with dense breasts as for women who do not have dense breasts, so there's a lot of interest in identifying more effective screening strategies for women with dense breasts," Dr Sprague told Medscape Medical News.
"One possible approach is to use ultrasound imaging in conjunction with mammography to identify cancers that may have been missed by the mammogram," he explained.
The choice of ultrasound for supplemental screening in women with breast cancer seems obvious. "It's been used for many, many years in the diagnostic imaging of breast cancer. If a woman has suspicious findings on a mammogram, one of the next steps in the workup may be to do ultrasound imaging of that specific suspicious finding," Dr Sprague said.
"Most clinics provide ultrasound imaging and have the capacity to use it for screening as well. Compared with something like MRI, it's not very expensive and almost every center has it," he said. "That's why it is increasingly being considered for use in screening in women with dense breasts, and that's why we focused on ultrasound."
The team used three microsimulation models, developed by the Cancer Intervention and Surveillance Modeling Network consortium, to examine the potential benefits, harms, and cost-effectiveness of supplemental screening with ultrasound. The models use evidence from clinical trials and observational studies to estimate the impact of various screening scenarios on outcomes.
For their study, Dr Sprague and colleagues took a lifetime horizon and federal payer perspective, and compared three strategies for women 50 to 74 years receiving biennial screening mammography: mammography alone; mammography plus screening ultrasonography after a negative mammography for women with extremely dense breasts; and mammography plus handheld screening ultrasonography after a negative mammography for women with heterogeneously or extremely dense breasts.
In secondary analyses, the models were examined as an annual screening regimen for women 40 to 74 years. No screening was the comparator in all cases.
The estimated benefits and harms of the screening strategies were similar in all three models.
For women 50 to 74 years, supplemental ultrasonography after a negative mammography prevented 0.36 additional breast cancer deaths per 1000 women with dense breasts, compared with mammography alone.
Furthermore, supplemental ultrasonography added 1.7 QALYs and resulted in 354 biopsy recommendations after a false-positive ultrasonography result per 1000 women with dense breasts.
The cost-effectiveness of ultrasonography was $325,000 per QALY gained, or $246,000 per QALY gained if ultrasonography was restricted to women with extremely dense breasts.
"The lack of cost-effectiveness comes from the relatively low cancer detection rate that we believe will occur among women who are routinely screened with mammography," Dr Sprague explained.
"Balancing that against the number of false-positive exams that would occur, it ends up being a lot of imaging with low cancer yield. But each of those imaging exams costs money, and the workup for so many false-positive exams to conduct those biopsies is expensive as well, which results in relatively poor cost-effectiveness."
"Certainly the benefit to harm profile of mammography screening itself is much more favorable than the results we are seeing with ultrasound screening," Dr Sprague said.
"Generally, mammography screening is considered to be one of our more cost-effective approaches to cancer prevention, although clearly there is a lot of controversy about the value of mammography screening in terms of when it should start and how often it should be done," he explained.
However, "the benefits of ultrasound that we observed in our study are relatively small, compared with the benefits of mammography," he pointed out. In addition, "the potential harms of ultrasound screening are quite high, compared with the harms of mammography screening, in terms of the number of biopsies that would be done in women who do not actually have breast cancer."
One of the primary concerns related to unnecessary biopsies is the anxiety that accompanies a biopsy, and the length of time it can take for the results to be reported, Dr Sprague noted.
There are, however, alternatives to supplementary ultrasonography on the horizon, which might give a more accurate picture of the breast cancer risk in women with dense breasts.
"One thing a number of researchers are very interested in is the potential for digital breast tomosynthesis to improve outcomes for women with dense breasts," he reported.
The technique, also known as 3D mammography, "acquires multiple slices of images through the 3-dimensional profile of the breast," he explained. "The radiologist is not just reviewing the 2-dimensional projection, but rather can look at all these images of different levels through the breast."
"It is hypothesized that it will allow radiologists to see breast cancers more clearly without the dense tissue interfering with their observations, and at the same time could prevent the dense tissue from causing artifactual appearances that look suspicious but aren't breast cancer," he added.
In fact, a computer simulation that Dr Sprague was involved with indicated that adding digital breast tomosynthesis to mammography was associated with an incremental cost per QALY of $53,893 (Radiology. Published online October 13, 2014). An additional 0.5 deaths were averted and 405 false-positive findings were avoided per 1000 women.
3D mammography "holds the promise of both increasing the cancer detection rate and reducing the false-positive rate, so there's a lot of interest now in evaluating that new technology," Dr Sprague concluded.
Funding was provided by the Breast Cancer Surveillance Consortium and the National Cancer Institute. Dr Sprague reports having worked briefly as a consultant for GE Healthcare.
Ann Inter Med. Published online December 8, 2014. Abstract
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