The national costs of false-positive mammograms and breast cancer overdiagnoses clock in at an estimated $4 billion per year, according to a study published in the April issue of Health Affairs.

Moreover, the costs of treating overdiagnosed cancer is likely to be higher in younger women, which could have implications for the debate over what age is appropriate to begin a routine screening program, according to study authors Kenneth D. Mandl, MD, professor at Harvard Medical School and director of the Children’s Hospital Informatics Program at Boston Children’s Hospital, and Mei-Sing Ong, PhD, a research fellow at Boston Children’s Hospital.

“The costs associated with false-positive mammograms and breast cancer overdiagnoses appear to be much higher than previously documented,” wrote Mandl and Ong. “Screening has the potential to save lives. However, the economic impact of false-positive mammography results and breast cancer overdiagnoses must be considered in the debate about the appropriate populations for screening.”

Mandl and Ong cited previous research estimating the cumulative probability of a recall for a false-positive scan after a decade of screening mammography at 61 percent. The U.S. rate of overdiagnosis—defined as the diagnosis of lesions that are unlikely to be clinically evident during a patient’s life—is estimated to be 22 percent or higher, however the study cited by Mandl and Ong that gave this estimate has been the subject of some controversy. The figure comes from a 2012 analysis by Bleyer et al published in the New England Journal of Medicine, and while some argued it helped demonstrate potential harms, others criticized assumptions made by the authors. A point-counterpoint article in the Journal of the American College of Radiology detailed these arguments.

To help illustrate the costs of false-positives and overdiagnosis, particularly in younger women, Mandl and Ong gathered expenditure data from a major private payer that included more than 700,000 women from 2011-2013, focusing on patients aged 40-59.

Results showed that average 12-month expenditures for each false-positive mammogram were $852 and that 11.1 percent of women in the study received a false-positive result.

For invasive breast cancer and ductal carcinoma in situ, the average 12-month expenditures totaled $51,837 and $12,369, respectively. Using the previous research on overdiagnosis rates to extrapolate these figures to an annual national cost, the total expenditure for false-positives and overdiagnosis is around $4 billion, according to the authors. They noted that these costs are higher than many previous estimates because past studies typically relied on Medicare data, which represent the lower end of reimbursement rates.

Mandl and Ong also explained that there is a greater risk of false-positive results among women ages 40-49, compared with those ages 50-59, and younger women with false-positives were more likely to use additional imaging services like MRI and ultrasound. Those diagnosed with breast cancer were more likely to undergo total mastectomy and breast reconstruction.

“The elevated risk of false-positive results, as well as the higher costs associated with breast cancer diagnosis and treatment in women ages 40–49, should inform the debate about the age at which breast cancer screening should commence,” wrote Mandl and Ong.