Ultrasound Adds to Mammography's Diagnostic Power for At-Risk Women

James Brice

April 03, 2012

April 3, 2012 — Annual screening mammography and breast ultrasound exams detect 34% more invasive breast cancers than mammography alone, according to a new multicenter study involving 2662 women with dense breasts and a moderately elevated risk for breast cancer.

Final results of the 3-year American College of Radiology Imaging Network (ACRIN) 6666 study showed that the benefits of screening ultrasound are tempered by more false-positives and negative breast biopsies.

The researchers also found that breast magnetic resonance imaging (MRI) after 3 years of screening mammography and ultrasound raises the diagnostic yield even higher (56% more invasive breast cancers detected), but at the cost of increased false-positives, higher financial expenses, and patient resistance to the procedure.

The study, which is published in the April 4 issue of JAMA, is the first major scientific inquiry to examine the specific, clinical relevance of breast cancers detected with screening ultrasound, principal investigator Wendie A. Berg, MD, PhD, from the Department of Radiology, University of Pittsburgh, Pennsylvania, said to Medscape Medical News.

The study is important because it addresses how the performance of breast imaging can be improved for women who have dense breasts or are inherently susceptible to breast cancer, Robert A. Smith, PhD, senior director of cancer screening at the American Cancer Society, said in an interview with Medscape Medical News. Dr. Smith was not involved in the study.

Dr. Berg characterized dense breast tissue as a "double whammy" in the context of cancer incidence and prevention. Women with dense breasts are up to 5 times more likely to develop breast cancer than women with fatty breasts, and mammography tends to miss cancers that reside in dense breasts, she said.

The trial, performed at 21 facilities, also confirmed the value of intensified screening using medical imaging for intermediate-risk women. Eight of 10 women in the study fell into that category, with 45% having a personal history of breast cancer, such as past lumpectomy and radiation therapy or a family member who was diagnosed with breast or ovarian cancer. Evidence from previous mammography of heterogeneously dense or extremely dense tissue was required.

The average age of participants at enrollment was 55 years, although women as young as 25 years were eligible when they met the study's at-risk criteria.

The women received breast ultrasound exams and screening mammograms in a single imaging session at the start of the trial, and then again 12 and 24 months later. Breast MRI was offered at the end of the series to 612 women who completed all 3 mammography and ultrasound screenings.

Improved Cancer Detection

Over the course of 3 years, 110 breast cancers were detected, with 89 cases involving invasive cancers.

Fifty-nine cancers (53%) were detected by mammography. Its diagnostic yield was the equivalent of 7.9 cancers per 1000 population.

The detection of invasive cancers increased 34% when screening ultrasound was performed. Its additional yield averaged 4.3 cancers per 1000 patients.

Only 8% of the cancers detected with mammography and ultrasound were palpable. This was half the expected rate of detected interval cancers for dense-breasted women, and lower than the 10% interval detection rate reported previously for women with fatty breasts, Dr. Berg noted.

Breast MRI raised cancer detection rate 56% and increased the yield by 14.7 cancers per 1000 (95% CI, 3.5 - 25.9 cancers per 1000; P = .004 vs mammogram plus ultrasound).

Clinical Costs of Higher Sensitivity

However, screening ultrasound and MRI involved added clinical costs that Dr. Smith characterized as "really quite significant."

Seven percent of women (95% CI, 6.3% - 7.8%) who underwent ultrasound screening required extra testing, including 5% referred for breast biopsies. Only 7.4% of the biopsies yielded a positive histological finding of cancer.

Of the 612 MRI participants, the rate of biopsy after mammography plus ultrasound was 6.2%; (95% CI, 4.4% - 8.4%). The rate of biopsy increased to 81 of 612 (13.2%; 95% CI, 10.7% - 16.2%) with the addition of MRI (P < .001). Only 19% of those procedures produced a positive cancer diagnosis.

Several additional factors led Dr. Berg and colleagues to recommend against MRI as a routine part of screening for intermediate-risk women, including that MRI is several times more expensive than ultrasound and access is limited because of required accessory equipment and specially trained personnel. In addition, breast MRI is not well-tolerated by women, Dr. Berg said.

Selected trial participants were offered the procedures for free at the 14 sites equipped to perform the procedures.

"We were surprised that only 58% of the women actually wanted to have the MRI," she said.

Screening ultrasound was beset by its own set of practice-related problems, Dr. Berg said. Low reimbursement rates and high operational costs make it no better than a break-even financial proposition, and healthcare facilities are discouraged from offering the service, she said.

Such problems could be addressed if the American Cancer Society recommends the combined mammography–ultrasound screening protocol for intermediate-risk women, as it did in 2007 when its guidelines were modified to acknowledge the benefits of screening MRI for high-risk women who are genetically susceptible to breast cancer.

A specific provision addressing breast cancer screening for the intermediate-risk group will be considered the next time ACS updates its guidelines, Dr. Smith told Medscape Medical News.

"We would certainly examine this study and others to determine if the data were sufficiently strong to provide clear guidance to women and referring physicians about whether different approaches to screening are needed," he said.

An ACS update on breast cancer screening guidelines was published in JAMA earlier this year. The update process, which typically takes about 12 months, will begin in late 2012, he said.

The study was funded by the Avon Foundation and grants from the National Cancer Institute. Dr. Berg has served as a consultant to Naviscan Inc and SuperSonic Imagine, has received research support from Naviscan, has prepared educational materials for Gamma Medica, has a research grant from Hologic Inc, and is on the medical advisory board of Philips Medical Systems. Dr. Smith has disclosed no relevant financial relationships. Full disclosure information for the authors is available on the journal's Web site.

JAMA. 2012;307:1394-1404. Abstract

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