Using Automated Breast Ultrasound to Reduce or Eliminate Interval Cancers

This is the first of a two-part series. Next week, Dr. Dean explores incorporating ABUS into clinical practice.

Breast density has been well established as a risk factor for cancer, increasing a woman’s risk by as much as four to six times. Numerous studies have also demonstrated that increased breast density makes cancer more difficult to detect with mammography. By masking the conspicuity of tumors, as breast density goes up, the accuracy of mammography goes down.

Breast tissue density has also been shown to be a major determinant of interval cancer, which is defined as cancer that becomes apparent clinically, usually because of a lump, between routine mammographic screenings. Retrospective studies have shown that 15 percent to 30 percent of interval cancers appear on the original screening mammogram that was initially interpreted as negative. The other 70 percent to 85 percent are not seen mammographically, even in retrospect.

A May 2011 article in the Journal of the National Cancer Institute showed that all interval cancers (true interval cancers and missed cancers) were diagnosed at a higher stage and grade than screen detected cancer. These findings continue to suggest a need for more sensitive modalities and revised screening protocols to improve the sensitivity and efficacy of breast cancer screening.

With demonstrated value as an adjunct to screening mammography, I believe automated breast ultrasound (ABUS) can be the modality that improves screening for women with dense breasts. I believe ABUS can be used to reduce interval cancers in women with dense breast tissue now being missed by relying on screening mammography only.

Finding Earlier, Smaller Cancers

In my Santa Barbara, Calif. practice, we have been offering ABUS since 2005 and have performed more than 8,000 ABUS exams on more than 3,000 women. As part of my experience with ABUS, I have participated in a prospective trial with SonoCine and more recently served as a reader in a pivotal ROC Reader Study for U-Systems.

At RSNA, I presented updated results to the 2010 European Radiology study, “Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts.” The update included 3,778 digital mammograms and automated breast ultrasound studies; all women had dense breast tissue (BIRADS 3 or 4 density score) or a high risk of breast cancer. Results showed that ABUS found 13 additional cancers, an increased yield of 76 percent over mammography alone. All the additional cancers found by automated breast ultrasound were invasive, and the average size of invasive cancers found was 9 mm with ABUS compared to 14 mm with digital mammography.

Specificity – 99.4%; PPV – 43.6%

Since we have been routinely offering ABUS exams, the number of interval cancers among screened women has dropped dramatically. We are finding smaller cancers, potentially a year or more before they would be palpable or visible on mammography. Earlier detection means different treatment options and potentially better outcomes. Before we began offering ABUS, interval cancers were not unusual in my practice, occurring 10 to 15 times every year. In 2011 there was just one interval cancer in patients with prior ABUS within 16 months. These results, if extrapolated over the dense breast patient population, could have a tremendous impact on effective breast cancer screening and overall breast health.

Avoiding Unnecessary Biopsies

The most common reason cited by physicians for not accepting ultrasound screening for breast cancer is the low Positive Predictive Value (PPV) of biopsy shown in the ACRIN 6666 study. But this trial involved a very high risk cancer population with a cancer rate of 12.6/1000. If a lesion was found in a woman in this very high risk group it would be difficult to justify short-term follow-up instead of biopsy.

To avoid low PPV using ABUS, the first step is to correlate the exam to the original mammogram. If a possible abnormality is identified the next step is to use focused breast ultrasound with color Doppler, to determine if there is a lesion, and to characterize the lesion using a systematic approach like the ACR BIRADS™ characterization method. If you are not familiar with breast ultrasound, there are a number of terrific courses available, and you should enroll in one before starting an ultrasound screening program.

RELATED: Introducing Whole Breast Ultrasound

In my practice we treat ABUS findings in the same way we treat screening mammography findings. The patient is recalled for the appropriate imaging to clarify whether there is cause for concern or not. That may mean magnification views, focused breast ultrasound, Color flow Doppler, or other imaging. Biopsy is never recommended on the basis of the initial ABUS finding alone. Therefore my PPV for lesions first identified by ultrasound and lesions first identified by mammography is similar, since the decision whether to biopsy is based on the work-up and not the initial screening. I was not a participant in the ACRIN 6666 trial but I think it may have blurred the line between screening and diagnostic ultrasound since these were hand-held, radiologist performed ultrasounds.

The radiologist also has to be able to confidently identify benign ultrasound findings like intramammary lymph nodes and fibroadenoma, or the biopsy rate will be unacceptably high.

The Balancing Act: Anxiety from False Positives or Missing the Opportunity to Prevent a Delayed Diagnosis of Breast Cancer

The use of adjunctive screening tools in breast cancer is frequently criticized - not for lack of sensitivity, but for the potential anxiety created by false positives. This concern is one of the most frequently cited objections to legislative efforts seeking to standardize the communication of breast density to women. However, what this argument fails to consider is the far greater stress and anxiety created by delayed diagnosis. The personal pain, cost and grief generated by a late diagnosis of breast cancer cannot be overstated. ABUS gives us the tool we need to prevent a great many delayed diagnoses.

While imaging tests detect suspicious areas, only a biopsy can provide a definitive diagnosis. Biopsies are an integral step in the diagnostic process and I do not hesitate to recommend a biopsy if the imaging results warrant it. At the same time, I wouldn’t recommend a biopsy on any screening study without a work up, whether it is a mammogram or an ultrasound. In a true screening scenario, when you work up each case, the PPV should be the same no matter how you first identified the lesion.

A practice utilizing ABUS will have significantly higher recall rates at the outset until the readers gain experience differentiating normal and benign findings, and identifying artifacts. Patient anxiety can be greatly reduced during this learning curve by initially having patients wait while ABUS studies are reviewed, and allowing time on the schedule for hand-held ultrasound if the radiologist feels it is needed. While recall rates for screening ABUS may always be higher than mammography, the increase is proportional to the additional cancers found.

What Density Score Suggests an ABUS?

There is a great deal of discussion about the classification of breast density and what BIRADS density score warrants the use of ABUS. While it is intuitive that there are more cancers missed by mammography the higher the density, in fact we have found occult cancers in density categories 2, 3, and 4.

This is where breast imagers may have to think differently than we’re used to. Rather than deciding for or against an ABUS recommendation solely on the BIRADS density score I also include the patient’s risk profile in my decision-making. From a protocol perspective, if I have a high risk patient with BIRADS 2 density rating, I discuss the surveillance options and let her decide. However, I recommend an ABUS exam for all patients with BIRADS 3 or 4 ratings. This is obviously an area where additional research will be of benefit, but the fact that a radiologist’s judgment of the density score may vary is not a reason to withhold density information or ABUS studies from women. Whether or not an ABUS is warranted is a judgment call, and radiologists are the best qualified physicians I know to make that judgment.

Down-staging Cancers

When we’re talking about reducing or eliminating interval cancers, we’re really talking about down-staging the cancers we find. In our 3,778 case study, we found 13 additional cancers using ABUS - all invasive, all node negative, and 12 of 13 were T1 (under 20 mm). These are early stage cancers with excellent prognoses and potentially less treatment required. Besides dramatically reducing the medical and financial impact of the cancer, we can’t ignore the social and emotional aspects of an early versus late stage cancer on women and their families.

I expect that the adjunctive use of automated breast ultrasound will have a huge impact on overall breast health. I believe it is the right thing to do for women with dense breasts.

Left: Retro areolar irregular mass seen in the coronal and transverse views. Right: Spiculated mass seen in the coronal and transverse views.

Multicyctic breast tissue seen in the coronal, transverse and sagital views. 

Judy Dean, MD, is a diagnostic radiologist in Santa Barbara, Calif., with more than 20 years of experience in women’s imaging. She completed an ultrasound and body imaging fellowship at Stanford University, and medical school and residency at Loma Linda University.