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Women with a false-positive mammography result have an increased risk of developing breast cancer over the following 20 years, according to a large population-based cohort study from Sweden.

In the cohort of nearly 500,000 women, the 20-year cumulative incidence of breast cancer was 11.3% among those with a false-positive result versus 7.3% among those without such a result (adjusted HR 1.61, 95% CI 1.54-1.68), reported Xinhe Mao, MSc, of the Karolinska Institutet in Stockholm, and colleagues.

In addition, women with a false-positive result were at increased risks of all-cause mortality (HR 1.07, 95% CI 1.04-1.11) and death due to breast cancer (HR 1.84, 95% CI 1.57-2.15), they noted in .

"This study suggests that breast cancer awareness should be emphasized long term for women with a false-positive mammography result," Mao and colleagues wrote, noting that development of personalized surveillance programs can be beneficial for these women.

"Given that false-positive results are common (i.e., approximately half [49.0%] of women in the U.S. and 20.0% of women in Europe will have at least 1 false-positive result after 10 screenings), our findings emphasize that they are also a critical public health issue," they added.

Looking at the reasons for this increased risk after a false-positive mammography result, Mao and colleagues focused on two possible mechanisms -- 1) the increased risk could be due to small tumors being missed at the previous mammography or to proliferative benign breast disease, or 2) the result may indicate a generally higher risk of breast cancer.

This matched cohort study was conducted in Sweden from January 1991 through March 2020 and included 45,213 women who received a first false-positive mammography result from 1991 through 2017, and 452,130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result).

The study also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study.

Median age of the total cohort was 52 (64.6% older than 50), and 92.3% had no family history of breast cancer.

Mao and colleagues found that the association between false-positive results and breast cancer risk was statistically significantly higher among women ages 60 to 75 (HR 2.02, 95% CI 1.80-2.26) compared with women ages 40 to 49 (HR 1.38, 95% CI 1.23-1.56).

The risk was also statistically significantly higher among women with lower breast density (HR 4.65, 95% CI 2.61-8.29) compared with women with higher breast density (HR 1.60, 95% CI 0.93-2.73), and for women who underwent a biopsy during the recall (HR 1.77, 95% CI 1.63-1.92) than for those without a biopsy (HR 1.51, 95% CI 1.43-1.60).

In addition, cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR 1.92, 95% CI 1.81-2.04), and were more common during the first 4 years of follow-up (within the first 2 years: HR 2.57, 95% CI 2.33-2.85; at >2 to 4 years: HR 1.93, 95% CI 1.76-2.12). There was no increase observed in the risk of breast cancer being detected on the contralateral side within the first 2 years of follow-up (HR 1.08, 95% CI 0.94-1.23).

Mao and team acknowledged that their results may not be generalizable due to differing screening intervals, false-positive rates, and strategies seen in Sweden compared with other countries. However, they also suggested that factors associated with false-positive results are similar between Europe and the U.S., and their findings "may be applicable to the U.S. context."

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