Mammogram Plus Ultrasound Screening Increases the Detection of Early Breast Cancer

Fran Lowry

December 02, 2009

December 2, 2009 (Chicago, Illinois) — Ultrasound plus mammography screening annually is significantly more efficient than mammography alone in detecting early-stage breast cancer in women who are at elevated risk for the disease, according to new research presented here at the Radiological Society of North America 95th Scientific Assembly and Annual Meeting.

Results from the American College of Radiology Imaging Network (ACRIN) 6666 trial showed that annual screening done every year for 3 years with mammography and physician-performed ultrasound found 29% more cancers, and 34% more invasive cancers, than mammography alone, Wendie A. Berg, MD, PhD, from American Radiology Services, Johns Hopkins at Green Spring Station in Lutherville, Maryland, reported.

The diagnostic yield from mammography alone was 53%, but jumped to 82% when ultrasound was added.

"That in and of itself tells you why there are some concerns about finding better screening combinations than just doing a mammogram alone," Dr. Berg told Medscape Radiology. "Importantly, the vast majority of the cancers that we found with ultrasound were the small invasive cancers that are likely to spread and could ultimately kill a person."

In 2008, Dr. Berg and her colleagues reported that screening with ultrasound and mammography significantly increased the detection rate of early breast cancers by 4.2 per 1000 in the first screen (JAMA. 2008;299:2151-2163).

ACRIN 6666 sought to determine that yield over 3 years.

"One of the issues that had never been looked at was whether we had to do ultrasound every year or whether you would catch some the first time you looked," she explained. "In fact, . . . we did find that we could increase detection significantly with each annual screening, so it does help to do ultrasound each year in addition to the mammogram. Overall, we had a significant increased detection across all 3 years."

ACRIN 6666, which was funded by the Avon Foundation and the National Cancer Institute, enrolled 2809 women at increased risk for breast cancer, from April 2004 to February 2006, from 21 sites in the United States, Canada, and Argentina.

The median age was 55 years (range, 25 to 91), and 88% had at least 40% dense breasts in year 1 of screening. Of the mammograms that were done in year 1, 35% were digital; this increased to 52% in year 3.

Overall, 53% of the women had a personal history of breast cancer and 1% were BRCA mutation carriers. In addition, 20% of the women met current American Cancer Society guidelines for magnetic resonance imaging (MRI) screening.

Of 7473 screens, 111 women were diagnosed with cancer, for a detection rate of 1.5%.

Thirty-three of the cancers (30%) were seen only with mammography, 32 (29%) were seen only with ultrasound, 26 (23%) were seen with both, and 20 (18%) were undetected. However, 9 of the cancers that were not detected with combined screening were found on MRI in the third year of the study.

The median size of the tumors was 11.5 mm (range, 1 - 55 mm), and 10 of 15 (67%) were node-negative.

Combined screening with mammography plus ultrasound found 91 of the 111 cancers, for a 29% absolute increase in cancer detection and a 34% absolute increase in invasive cancer detection, Dr. Berg noted.

Screening ultrasound was just as beneficial in women who had digital mammography or film, and in those with or without a personal history of breast cancer.

ACCRIN 6666 also screened a subset of 612 patients with MRI in year 3 of the study.

MRI increased the detection of breast cancer another 56% in that subgroup of patients, and increased the detection of invasive cancers by 67%.

"Even though this was a relatively small number of patients, it was clearly significant. If you really want to find as many of the cancers as you possibly can, doing the MRI was even more sensitive, by far, than the combination of mammography and ultrasound," Dr. Berg said.

The downside to adding ultrasound or MRI screening was the increase in false-positives. With the addition of ultrasound, there was a 7% to 8% increase in recalls for additional imaging or follow-up. Overall, 3% more women were recommended for short-term follow-up, and fewer than 2% of those cases turned out to have cancer.

One in 20 women who underwent the combination of mammography and ultrasound had a biopsy. Only 10% of the suspicious lesions seen on ultrasound turned out to be cancer.

"With mammography, that rate is between 25% and 35%, so with the addition of ultrasound, there were more biopsies for findings that were not cancer," Dr. Berg told Medscape Radiology.

Dr. Berg maintains that a needle biopsy done under ultrasound guidance is a minimal procedure, akin to going to the dentist.

"It's done in about 15 minutes with lidocaine. I've had many, many conversations with women about this, and the vast majority say it's not a big deal. I'd much rather be sure there's no cancer," she told Medscape Radiology. "They are willing to accept these risks."

Recall for additional evaluation occurred in 14% of women who were screened with MRI. However, when biopsies were done, they detected cancer 25% of the time. "That's a reasonable number," Dr. Berg said.

The study confirms the benefit of MRI in women with an elevated risk for breast cancer.

The next step is to do a randomized controlled trial to determine if there is reduced mortality as a result of adding either MRI or ultrasound to mammography.

"Such trials are extremely expensive and take many, many years, and it may be hard for women and their doctors to accept randomization not to have additional screening," Dr. Berg said.

She said that her center has been offering combination screening with ultrasound plus mammography or MRI plus mammography to appropriately selected women for years.

Most women accept the offer. "The vast majority of women who are offered it do choose to have ultrasound because they recognize the potential benefit of detecting these invasive cancers early. They also know that the test is painless and requires no radiation or injection. The facility has been willing to train dedicated technologists so that we can offer it."

Dr. Berg added that MRI is not as well tolerated because it requires an injection and because some women are claustrophobic. Insurance coverage for MRI varies, which is also a factor in its use.

Women must know their risk factors and discuss these with their physician, she concluded.

"We now have the ability to tailor screening based on a woman's risk factors as well as breast tissue density. If they are at increased risk, they should consider an MRI if they can tolerate it. If not, then ultrasound is now a viable alternative at centers with trained personnel. We know it helps detect early cancers."

Asked to comment on this study, Stamatia V. Destounis, MD, from the University of Rochester School of Medicine in New York, told Medscape Radiology that the information provided by Dr. Berg is very significant.

"As breast imagers, we have realized the significance of additional tools in the evaluation of patients at higher risk for breast cancer," she said. "Ultrasound is a noninvasive test that is well tolerated and accepted by women, so it is indeed good news that the data and follow-up on these high-risk patients reveal benefit from adding the ultrasound examination."

Dr. Destounis noted that these high-risk patients might have difficult dense breast patterns on mammography, making the detection of small invasive tumors a challenge.

The increase in false-positives increases the work-up rate, but Dr. Destounis said she believes that most women are happy to undergo additional testing to make certain they are okay. "An ultrasound guided needle biopsy is typically a procedure that can be done quickly and with minimal patient discomfort."

Dr. Berg and Dr. Destounis have disclosed no relevant financial relationships.

Radiological Society of North America (RSNA) 95th Scientific Assembly and Annual Meeting: Abstract VB31-12. Presented December 1, 2009.


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