Study Links False-Positive Mammography Result to Increased Breast Cancer Risk
Findings detailing long-term breast cancer outcomes for women who received a false-positive result underscore the significance of false-positive results as a critical public health issue.
The risk of developing breast cancer is elevated in women who received a false-positive mammography result compared to those who did not, but the extent of the risk varies by individual characteristics and follow-up, according to study results published in JAMA Oncology.1
Participants in the population-based, matched cohort study conducted in Sweden from January 1, 1991, to March 31, 2020, included 45,213 women aged 40 to 74 who received a first false-positive mammography result between 1991 and 2017 and 452,130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result).
Another 1113 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 were included in the study pool. Statistical analysis was performed from April 2022 to February 2023.
Investigators followed up with women from the date of the next screening after their index mammography until the first diagnosis of breast cancer, death, emigration, or March 31, 2020, whichever came first, to investigate breast cancer incidence after a false-positive result. Investigators conducted a similar protocol to investigate mortality after a false-positive result, following up with women until death, emigration, or March 31, 2020, whichever came first.
The study found that women with a false-positive mammography result had an increased risk of subsequently developing breast cancer, persisting up to 20 years, but the degree of risk varied among host characteristics. Those who face a higher risk of developing breast cancer after a false-positive result include women aged 60 to 75 years, women who underwent a biopsy at recall, women with low mammographic breast density, and women with large tumors. Study authors noted that no association was found between a false-positive mammography result and other tumor characteristics or molecular subtypes, aside from tumor size.
Investigators also found that women with a false-positive result had an increased risk of all-cause mortality and death due to breast cancer.
Study results further showed that women who had tumors on the ipsilateral side to the false-positive result had an elevated risk of breast cancer, and that women were most at risk for developing breast cancer on the ipsilateral side within the first 4 years of follow-up. These findings shed light on potential explanations as to why women are more likely to develop breast cancer after a false-positive result, as the increased risk may be due to small tumors being missed at the previous mammography or to proliferative benign breast disease among the population.
Investigators alternatively hypothesized that a false-positive result may serve as a marker of an overall increased risk of breast cancer. This hypothesis was made considering study findings that demonstrated that after the first 4 years of follow-up, a similar and long-term increased risk of breast cancer on the ipsilateral and contralateral sides existed among women with a false-positive result compared with those without. Further studies are needed to explain this long-term risk and the factors that affect it, like those related to hormones or genetics.
Although mammography screening programs are associated with a reduction in breast cancer mortality of more than 20%,2-4 false-positive mammography results are common and harmful (ie, approximately half [49.0%] of women in the US and 20.0% of women in Europe will have at least 1 false-positive result after 10 screenings).5,6 These misleading outcomes may cause psychological distress and anxiety in recipients, potentially influencing future attendance in screening programs.
Findings from the current study, considered in tandem with the prevalence of false-positive results among women, underscore the significance of false-positive results as a critical public health issue.
Overall, the study suggests that women who receive a false-positive mammography result should remain aware about their long-term risks. For this population, study authors noted that developing individualized risk-based breast cancer screenings could be helpful.
“It’s important to accentuate a long-term awareness of breast cancer in women who get false-positive mammography results,” said Xinhe Mao, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet in Sweden, in a news release.7 “It might be beneficial to draw up personal monitoring programmes for these women with careful follow-ups over the years immediately following.”
