Women with dense breasts are at increased risk for developing breast cancer, as well as for that cancer to be missed by standard screening methods. Wendie Berg, MD, PhD, FACR, Professor of Radiology and The Dr. Bernard F. Fisher Chair for Breast Cancer Clinical Science at the University of Pittsburgh School of Medicine and Magee-Womens Hospital of UPMC, and colleagues conducted a study to determine if annual technologist-performed screening ultrasounds improve breast cancer detection when performed after digital breast tomosynthesis for women ages 40-75 with dense breasts. The results were published in the Journal of Clinical Oncology (2023; doi: 10.1200/JCO.22.01445).
For the study, 6,179 women underwent three rounds of annual screening, interpreted by two radiologist observers, and had appropriate follow-up. The data showed that adding ultrasound did indeed improve breast cancer detection over digital breast tomosynthesis alone, though with modest benefit. Overall sensitivity of digital breast tomosynthesis was 69 percent, whereas adding ultrasound increased sensitivity to 84 percent. "Overall added cancer detection rate of ultrasound screening after digital breast tomosynthesis was modest," the researchers noted in the paper, "but potentially overcomes substantial increases in false-positive recalls and benign biopsies." In an interview with Oncology Times, Berg discussed the findings.
1 Why did you and your colleagues decide to pursue this research now?
"There is increasing public awareness about the risks of dense breasts-both the increased risk of developing cancer and, more problematic, the risk of cancer being hidden by dense tissue on a mammogram. About 40 percent of women having mammograms have dense breasts (heterogeneously dense or extremely dense). About 30-40 percent of cancers are hidden in dense breasts.
"Currently, 37 states plus DC require some density information with the mammogram results letters (https://tinyurl.com/5dz4an2a). Florida had legislation requiring this, but it expired on the last day of June 2023. As of September 2024, the FDA will require nationally standardized mammogram results letters that inform women their breasts are either dense or not dense, that dense tissue makes it harder to find cancer on a mammogram, and it also raises the risk of developing breast cancer. In women with dense breasts, the letter must also state that 'other imaging tests in addition to a mammogram may help find cancers.'
"We have strong evidence of the benefit of screening MRI in women at high risk or with extremely dense breasts, but there are no clear guidelines for women with heterogeneously dense breasts, and not all women who qualify for an MRI can access or tolerate it. Ultrasound is an alternative to MRI, but there were very few published studies evaluating ultrasound after tomosynthesis (3D mammography), especially incidence screening."
2 What were the key findings from this study?
"Consistent with a large body of work in the United States and Europe, our study showed that mammography alone, even using tomosynthesis, missed over 30 percent of cancers in dense breasts, and adding ultrasound each year improved cancer detection. The cancers found by screening ultrasound were mostly invasive (84%) and node-negative (81%)-the types of cancers that need treatment. We observed a very low interval cancer rate (cancers found because of symptoms). Adding ultrasound also produced additional testing for findings that were not found to be cancer in about 4 percent of women each year."
3 What are the implications of the research?
"The USPSTF just issued draft guidelines for breast cancer screening that fail to adequately address the limitations of mammography in women with dense breasts or the overlapping large group of women at higher-than-average risk. Our work adds to a large body of evidence showing improved detection of invasive cancers by adding ultrasound to mammography in women with dense breasts. MRI finds many more cancers than ultrasound, but not all women qualify for or can tolerate MRI. Many women with dense breasts and a family history or personal history of breast cancer or other risk factors meet 'high-risk' criteria and there are other national guidelines (including NCCN, ACR, ACS) that recommend adding MRI each year, or ultrasound if MRI is not possible. But many women and their doctors are not aware of these guidelines.
"The most important takeaway is that, separate and distinct from the increased risk of developing breast cancer, in women with dense breasts at least 30 percent of cancers are hidden on mammography. Women and their health care providers should be comfortable discussing supplemental screening options such as ultrasound or MRI-and efforts to standardize insurance coverage are equally important. Currently, 21 states plus DC have laws requiring coverage of at least some additional breast screening beyond mammographic (19 MRI or ultrasound and two ultrasound). The Find It Early Act has been introduced in Congress by Reps. Rosa DeLauro (D-CT) and Brian Fitzpatrick (R-PA) requiring a national standard so that all women can afford access to early detection of breast cancer (http://www.FindItEarlyAct.org)."