An analysis of more than half a million breast-cancer screenings complemented by a long follow-up period has buttressed the theory that women with false-positive results at mammography are at increased risk of later developing breast cancer.

In the study, the association was particularly strong in women who had calcifications vs. other features at mammography.

Perhaps most notably, the researchers observed a highly increased risk in women who had more than one false-positive exam coupled with changes in mammographic features over time.

The study, lead-authored by Xavier Castells, MD, PhD, Autonomous University of Barcelona, is running online ahead of print in Radiology.

Castells and colleagues retrospectively reviewed the cases of 521,200 women between the ages of 50 and 69 who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and were observed until December 2012.

After adjusting for screen-detected and interval cancers, and for screen-film and digital mammography, the team found:

• When compared with women with negative mammograms, the age-adjusted hazard ratio of cancer in women with false-positive results was 1.84 (95 percent confidence interval for this and all hazard ratios below).
• The risk was higher in women who had calcifications, whether they were (hazard ratio, 2.73) or were not (hazard ratio, 2.24) associated with masses.
• Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (hazard ratio, 9.13).
• The risk of breast cancer in women with false-positive results was similar between screen-detected (hazard ratio, 1.77) and interval (hazard ratio, 2.01) cancers.

In their study discussion, the authors suggest that the mammographic features in women with false-positive results might be worth considering when planning follow-up protocols.

They point to the long follow-up period and large sample size as strengths of their study. They acknowledge as a weakness a substantial number of cases in which they were unable to ascertain whether tumors were found in the same location as some mammographic features.

“As with other variables, such as family history, age and breast density, previous screening results may be useful to improve the accuracy of risk-prediction models,” the authors conclude. “Population-based breast cancer screening programs should consider the antecedent of having a false-positive result for recommending yearly follow-up.”

The Spanish study comes soon after one in the U.S. showed that women with false-positive findings at screening are at increased risk for at least 10 years.