A false-positive mammogram could be an indicator of underlying pathology that could result in breast cancer, according to a study published April 5 in the Journal of the National Cancer Institute.

Women with false-positive mammography findings have suspicious patterns in their breast tissue, which may indicate a higher risk for breast cancer among this population than in women without these suspicious patterns. However, few studies have examined this link, and existing studies have reported contradictory results.

My von Euler-Chelpin, PhD, of the department of public health at University of Copenhagen, and colleagues sought to determine whether women with false-positive results have a higher long-term risk for breast cancer compared with women who test negative. 

The researchers gathered data from a long-standing population-based screening mammography program in Copenhagen from 1991 to 2005. They evaluated the risk of breast cancer and ductal carcinoma in situ in women who had received false-positive test results between the ages of 50 to 69 years. The age-adjusted relative risk of breast cancer for women who had tested false-positive for breast cancer was compared to women who had tested negative.

A total of 58,003 women were included in the analysis.

von Euler-Chelpin and colleagues found that women who had tested negative for breast cancer had an absolute cancer rate of 339/100,000 person-years at risk, compared to women who tested false-positive, who had an absolute cancer rate of 583/100,000 person-years at risk. The figures translate into a 67 percent higher risk of breast cancer among women with a false-positive test than in women without a false-positive result.

The relative risk of breast cancer in women with false-positive tests was statistically significantly higher than in women who tested negative even six or more years after the test. However, the researchers wrote, "The excess breast cancer risk in women with false-positive tests may be attributable to misclassification of malignancies already present at the baseline assessment."

The researchers also observed a marked excess risk two to four years after the false-positive. At that point, comparison with previous mammograms could reveal eventual changes in suspicious tissue.

von Euler-Chelpin and colleagues noted that excess risk dropped over time, with the 65 percent excess risk of breast cancer in women with false-positive results from 1994 to 1998 declining to 31 percent from 2001 to 2005.

The improvement coincided with the introductions of high-frequency ultrasound in 2001, stereotactic breast biopsy in 2002 and standard bi-directional mammography in 2004. 

There are two hypotheses about the reason behind excess breast cancer risk. Malignancies may be misclassified at baseline assessment, or some women without malignancies at baseline may have a biological susceptibility to the development of breast cancer. The study findings—more than double risk at the first screen following the false positive and reduced excess risk in the later technology phase—support the misclassification hypothesis, according to von Euler-Chelpin et al.

The authors also cautioned that the experience of a false-positive may cause anxiety, which may discourage women from attending regular screenings. “The long-term excess risk of breast cancer found in women with false-positive tests stresses the need for their adherence to regular screening. … Based on the findings in this study, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening."

von Euler-Chelpin and colleagues recommended researchers collect longer follow-up data for screening after the introduction of new technology.