Adding either tomosynthesis or ultrasound scanning to standard mammography may enable detection of more breast cancers in women with dense breasts, according to an interim analysis of a multicenter screening trial.
In a cohort that included more than 3000 women with dense breast tissue, for whom standard mammograms had not detected any malignant lesions, the addition of tomosynthesis or ultrasound scans picked up 24 additional cancers, 23 of which were invasive.
Of these screening-detected cancers, 12 were detected by both tomosynthesis and ultrasound, one was detected only by tomosynthesis, and 11 only by ultrasound.
This extrapolated to an incremental cancer detection rate for tomosynthesis of 4 breast cancers per 1000 women screened, and for ultrasound, 7.1 per 1000.
The findings were presented at the 10th European Breast Cancer Conference (EBCC-10) and were published onlineMarch 9 in the Journal of Clinical Oncology to coincide with the meeting.
Study author Nehmat Houssami, MBBS, PhD, a professor of public health at the University of Sydney, Australia, pointed out that until now, there have been no prospective trials comparing the addition of ultrasonography or tomosynthesis to standard mammography screening for women with dense breast tissue.
"These findings will have immediate implications for both screening practice and for guiding new research in dense breasts," she said.
A variety of breast imaging modalities have been evaluated as adjunct screening for women with mammography-dense breasts, the authors note. Interest intensified after legislative measures were enacted in some US states that require that women be informed about the their breast density and adjunct screening.
False Recall Rates Noteworthy
Study results have been mixed as to the effectiveness of adjunct screening with ultrasound. One study, for example, found that the addition of ultrasound screening to standard mammography had little impact on detection and that it increased harms and drastically increased costs.
Conversely, another study reported that use of ultrasonography, in addition to mammography, should be routine in the screening of women with dense breast tissue and that the positive predictive value of screening ultrasonography rose significantly during the first 4 years after the breast density notification law was passed.
Ultrasound screening for women with dense breasts is resource intensive and increases false recalls and costs, yet is of debatable beneﬁt, note Dr Houssami and colleagues.
Digital breast tomosynthesis (quasi 3D mammography), on the other hand, is a relatively novel technique that could potentially increase the rate of breast cancer detection and reduce false positive ﬁndings, say the authors.
Some data, they note, show that adjunct tomosynthesis yields incremental breast cancer detection, in the range of 1.2 to 2.7 per 1000 screens. On the basis of these findings, the modality has been touted as a potential adjunct screening modality for women with dense breasts.
In the current study, adjunct tests caused 3.3% more false positive recalls, Dr Houssami told Medscape Medical News.
"The percentage of false positive recalls did not differ between these tests, but that may be because the radiologists in the study were experienced in using ultrasound for screening dense breasts," she said.
There were 53 false positive recalls with tomosynthesis and 65 with ultrasound (P = 0.26).
The number of biopsies performed as a result of false positive recalls also did not differ significantly between the two techniques: 22 for tomosynthesis and 24 for ultrasound (P = .86).
Although ultrasound did detect more cancers than tomosynthesis, tomosynthesis still may have an edge on ultrasound.
Dr Houssami pointed out that ultrasound is a separate test, is time-consuming, and if not performed by someone with experience, can lead to a high rate of false negative results.
Tomosynthesis, however, is a type of mammography, can be performed as part of standard 2D mammography screening, or possibly instead of it, because it did detect more than 50% of the additional breast cancers in the study population.
Although tomosynthesis has the potential to become the primary method for breast cancer screening, without requiring an extra screening procedure, Dr Houssami cautioned that more data are needed.
"We do not have enough evidence to recommend that tomosynthesis can be used instead of standard mammogram, but evidence from our study could be used to inform such study," she said. "For example, we can use it to plan a trial where women known to have dense breasts can be triaged to tomosynthesis screening without adjunct tests, but we will need more research on the impact of such an approach.
"Having just the one screening test would be ideal for the woman, and that is why tomosynthesis will be more feasible for dense breasts, moving into the future," Dr Houssami added.
Replacing 2D Mammography
At least one institution has already moved away from standard 2D mammography for the screening of women with dense breasts.
Commenting on the study, Prasanna Kumar, MD, an assistant professor in the Department of Diagnostic Radiology, Roswell Park Cancer Institute, Buffalo, New York, noted that tomosynthesis is not universally available in screening facilities, so the alternative is ultrasonography.
"But ultrasonography is operator dependent, and it involves more time — as a screening protocol, you have to screen the whole breast bilaterally, and it is time consuming. It also has high false positive rates," he told Medscape Medical News.
At Roswell Park, tomosynthesis is used as the primary screening method for women with dense breast tissue, not as an adjunct to standard mammography. "If we see any abnormality on tomosynthesis, then we proceed with targeted ultrasound as a complementary measure, to correlate with the finding," Dr. Kumar said. "Since we are a tertiary cancer center, in our population, we don't do ultrasound as a screening modality as of now. But it's done elsewhere."
At Roswell Park, tomosynthesis is currently being used as a single screening modality for women with dense tissue. "But it will be expanded to include all screening mammography women once we have the new equipment ready," he explained.
An ACRIN 6666 large clinical trial was undertaken to develop guidelines for the screening of women with dense breast tissue. "Ultrasound screening women with dense breast tissue can be done," he added, "but it has high false positive rate, about 28%."
Many factors are involved for implementation, explained Dr Kumar, such as the availability of equipment and trained personnel. "There is no generally agreed consensus for screening of dense breast tissue, and it is still evolving," he said.
Dr Houssami and colleagues undertook a prospective, multicenter trial of the use of tomosynthesis and ultrasound for adjunct screening of women with dense breasts.
The patient cohort included 3231 women with dense breasts who had negative results on mammography screening (median age, 51 years; range, 44 to 78 years).
Tomosynthesis or ultrasonography detected suspicious ﬁndings that warranted further investigation in 131 of the participants.
A total of 24 women had screen-detected lesions that were malignant; these included invasive ductal (n = 18), invasive lobular (n = 4), mixed invasive type (n = 1), and ductal carcinoma in situ (n = 1).
The positive predictive value for recall leading to biopsy was 13 per 35 screens (37%) for tomosynthesis, and 23 per 47 screens (48%) for ultrasound.
There were other findings that were considered probably benign but were not recalled for work-up and were recommended for short-term imaging review. For tomosynthesis, these were observed in 150 (4.7%) screens; for ultrasonography, they were observed in 57 (1.8%) screens.
The study was funded by research support to one coauthor from the Associazione Italiana per la Ricerca sul Cancro and the University of Genoa. Dr Houssami received a National Breast Cancer Foundation Australia Breast Cancer Research Leadership Fellowship.
10th European Breast Cancer Conference (EBCC-10): Abstract 3 LBA, presented March 8, 2016.
J Clin Oncol. Published online March 9, 2016. Abstract