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      A false-positive finding on mammography points to a greater chance of breast cancer long-term, possibly because of underlying pathology or initial misclassification, a population-based study suggested.

      Women with any type of false-positive test faced an adjusted 67% higher risk of breast cancer after a false-positive test than women who had only negative screens (P0.001), My von Euler-Chelpin, PhD, of the University of Copenhagen, and colleagues found.

      That risk remained significantly elevated from 6 to more than 12 years after a false-positive test result, with relative risk point estimates of 1.58 to 2.30 (all P≤0.001), the researchers reported in the May 2 issue of the Journal of the National Cancer Institute.

      “It may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening,” they recommended, though acknowledging the risk of causing extra anxiety.

      It’s possible that the higher risk just reflected that cancers had been missed, perhaps because of older, less sensitive diagnostic tools, von Euler-Chelpin’s group noted.

      Their study examined outcomes for the 58,003 women, ages 50 to 69, who participated in Copenhagen’s population-based mammography screening program from 1991 to 2005. At that time, false-positive test rates ranged from 5.6% to 1.4%.

      The overall absolute cancer rate was 339 per 100,000 person-years at risk compared with 583 per 100,000 person-years at risk over the mean follow up of 10.9 years.

      When they stratified the analysis by phases of technology used in the program, risk of breast cancer with equal follow-up time were elevated for the false-positive group from the mid-1990s evaluated with clinical examination, film-screen mammography, and needle biopsy for suspicious findings (relative risk 1.65 versus negative-only screening, 95% CI 1.22 to 2.24).

      However, the risk was not significantly elevated for the false-positive group from the early 2000s, after introduction of high frequency ultrasound and sterotactic biopsy (RR 1.31 versus negative-only screening, 95% CI 0.87 to 2.00).

      Another factor favoring misclassification as an explanation was the “finding of a more than doubled risk at the first screen following the false-positive test,” they noted.

      However, the persistently elevated risk supported the idea of biological susceptibility, similar to the excess breast cancer risk seen among women with benign breast lesions, the group argued.

      “Women with false-positive tests manifest suspicious mammographic patterns in their breast tissue, including tumor-like masses, suspicious microcalcifications, skin thickening or retraction, recently retracted nipples, distortions, asymmetric densities, or suspicious axillary lymph nodes,” von Euler-Chelpin and colleagues noted.

      Despite a thorough assessment to exclude malignancies at baseline, these suspicious patterns in breast tissue may eventually develop into detectable cancer, they explained.

      “Even with newer screening methods, women with false-positive tests should be encouraged to use regular mammographic screening because a false-positive test may indicate underlying pathology that could result in breast cancer,” the group concluded.

      The study had some limitations: false-positive tests classified by right or left breast were not included in the dataset. Also, the sample sizes and follow-up times for the analysis by technology period were smaller than those in other analyses.

      The authors noted that the cumulative risk of false-positive was around 16% in their screening program, whereas estimates put that risk at roughly 60% for mammography as done in the U.S.

      “Considering the large difference in recall rate between the U.S. and Denmark, one may, on the basis of who is selected for recall, expect the breast cancer risk in the large group of U.S. women with a false-positive test to be closer to that of test-negative women than what we found for the more restricted group of Copenhagen women with a false-positive test,” they wrote.

      But there are likely subgroups of American women with risks similar to those found in the Copenhagen group after a false-positive given that biology and screening technology are fairly similar across the two countries, the group noted.

      One co-author reported employment with NovoNordisk.

      Primary source: Journal of the National Cancer Institute

      Source reference:
      Von Euler-Chelpin M, et al “Risk of breast cancer after false-positive test results in screening mammography” J Natl Cancer Inst 2012; 104; DOI: 10.1093/jnci/djs176.


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