Mammography: Can It Be Improved?

Common Sense 101: if benefits outweigh the costs, generally people will opt in to whatever action is under consideration. If you can prevent or reduce your chance of death from cancer by early screenings at a nominal fee, you will probably get screened.

Now throw a twist into the equation. Say that screening is only 50 percent effective at catching early cancer. On the benefit side, screening will still prevent or reduce cancer. On the cost side, you may not catch a tumor; you may be exposing yourself to harmful radiation (which ironically could contribute to the cancer you’re trying to prevent), emotional stress from false positives and possible physical harm from false negatives; and you’re spending money on a service that only works half the time. (Using the same idea, if your airbag only worked in 50 percent of accidents, would you pay for it to be installed in your car, or would you demand that auto manufacturers developed an airbag with 100 percent efficiency?)

A study published in the May 14 issue of JAMA will likely continue the debate over gold standards in clinical care – early mammograms in breast cancer, colonoscopies in colon cancer, etc – and whether the costs are worth the benefits. The American College of Radiology and Radiological Society of North America write on a public information Web site that mammography plays “a central part in early detection of breast cancers because it can show changes in the breast up to two years before a patient or physician can feel them…. Research has shown that annual mammograms lead to early detection of breast cancers, when they are most curable and breast-conservation therapies are available.” Government guidelines recommend women (of average risk) get a screening mammography every year beginning at age 40.

That mammograms save lives does not seem to be in question. But how many lives does the screening save, and can it be done better? The authors note that an analysis of 7 randomized trials found that the point estimate of the reduction in mortality from screening mammography was 22 percent in women aged 50 years or older and 15 percent among women between 40 and 49 years. Christiane Kuhl, University of Bonn, writes in an editorial from the same JAMA issue that sensitivity can be as low as 25 percent (for BRCA1 mutation carriers), and a large trial showed that even in average-risk women sensitivity was only 55 percent.

Wendie Berg and colleagues acknowledge that methods “to address improving detection despite dense breast tissue are needed.” They note that supplemental screening ultrasound “has the potential of depicting small, node-negative breast cancers not seen on mammography, and its performance is improved in dense parenchyma.”

With support from the Avon Foundation and National Cancer Institute, Berg et al. compared the diagnostic yield (the proportion of women with positive screen test results and positive reference standard, a combination of pathology and 12-month follow-up) and performance of screening with ultrasound plus mammography with mammography alone in women at elevated risk of breast cancer.

Kuhl called the results of the study impressive. Ultrasound in combination with mammography was associated with a 55 percent increase in diagnosing breast cancer compared with mammography alone. The sensitivity of detection was 77.5 percent for patients in the ultrasound/mammography group, compared with 50 percent for mammography only patients.

According to the authors, 40 of the 2,637 patients included in the analysis set (reference standard) were diagnosed with cancer, 39 of whom had breast cancer. Twenty of the 40 cancers (50 percent) were identified on mammography only for a yield of 7.6 per 1000 women. The ultrasound plus mammography screening depicted 31 cancers (77.5 percent), producing a yield of 11.8 per 1000 women and an increased yield due to ultrasound of 4.2 per 1000 over mammography alone. (Both yield and sensitivity were significant at p=0.003.)

The specificity of mammography alone was 95.5 percent, while the ultrasound plus mammography was 89.4 percent specific (p<0.001).

*Remember: sensitivity = [true positives/(true positives+false negatives)] = the true positive rate. Specificity = [true negatives/(true negatives+false positives)] = the true negative rate.

So, why not add ultrasound to all mammography screening in the future? Well, besides the cost and lack of evidence from randomized trials on mortality endpoints, as Kuhl points out, the number of false positives increases. (Lower specificity = more false positives.)

Yet your view of a false-positive may be relative – Kuhl writes that what these women “fear the most is a late diagnosis of breast cancer. If these women were told that screening mammography detects only half of the cancers, they may perceive that fact as the real threat they want to be protected against, not false-positive diagnoses.”

Women have trusted in mammography for many years, Kuhl writes, and radiologists are reluctant to educate women on the actual diagnostic performance of mammography for fear of reducing screening participation due to a lack of perceived alternatives.

Is there anything in the alternative category besides ultrasound? Berg et al. have an ongoing study using contrast-enhanced breast magnetic resonance imaging (MRI) within 8 weeks of the final 24-month mammography and ultrasound screening round, which they suggest may soon “shed some light on the possible competitive roles of ultrasound and MRI as adjuncts to mammographic screening for breast cancer.”

Kuhl concludes that it may be “time to carefully reconsider” the concept of mammographic screening, perhaps using individualized screening schemes tailored to individual women. Whether ultrasound or MRI will be more appropriate for this purpose, Kuhl says – and whether these studies impact screening participation and breast cancer mortality – remains to be seen.

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