False-positive mammography results are common, but a large population-based cohort study conducted in Sweden found an elevated incidence of developing and dying of breast cancer up to 20 years after a false-positive result.
Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer compared with those who did not have a false-positive result.
However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.
The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and "can be used to develop individualized risk-based breast cancer screening," the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm, said.
The findings were published online on November 2 in JAMA Oncology.
About 11% of women in the US and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.
To assess long-term outcomes after a false-positive result, Mao and colleagues compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 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.
Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio [aHR], 1.61).
Breast cancer risk was higher in older women — those aged 60-75 years (HR, 2.02) — vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).
After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) vs the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs 1.47 for smaller tumors).
The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result vs no false-positive result; 95% CI, 0.89-1.25).
This study is the first to show that "women with a false-positive result are at increased risk of death from breast cancer," Mao and colleagues concluded. This finding is "most probably associated with the increased breast cancer incidence," given that the prognosis of patients with breast cancer was similar among those who had a false-positive result vs those who did not.
The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false-positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Mao and colleagues noted.
When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.
Overall, the findings indicate that clinicians " should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result," Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, told Medscape Medical News.
Miglioretti, who has led research on false-positive mammography results and approaches to reduce false-positives, noted that "this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium (BCSC) showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future."
The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Miglioretti said.
However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.
It is "important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results," Miglioretti said.
This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Mao is supported by a grant from the China Scholarship Council. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at email@example.com or on Twitter: @SW_MedReporter.