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A recent report sheds light on how much false-positives and overdiagnosis of breast cancer cost. Additionally, new research examines the impact of the number of live births on future heart health in the mother and provides further evidence of the efficacy of cfDNA testing.
An analysis of routine mammography in women aged 40 to 59 shows that false-positive results and overdiagnosis of breast cancer are costing the United States $4 billion every year. Published in Health Affairs, the report on a nationally representative sample suggests greater expenditures-and more economic impact-for false-positives than had been previously thought.
Using medical claims data from a major US healthcare insurance plan for 702,514 women spanning 2011 to 2013, researchers from Boston Children’s Hospital and Harvard University assessed mammography outcomes in women aged 40 to 49 and 50 to 59 who underwent routine screening.
The authors calculated a false-positive rate of 11%--or 3.2 million women receiving such results. That, taken together with overdiagnosis of invasive breast cancer and ductal cancer in situ (DCIS) at rates of 22% and 86%, respectively, brought the price tag for women aged 40 to 59 to $4 billion annually.
The average cost of each false-positive mammogram, invasive breast cancer, and DCIS was $852, $51,837, and $12,369, respectively. In women aged 40 to 49, an average of $867 was spent related to false-positive mammograms, compared with $833 for women aged 50 to 59. The difference was largely ascribed to more use of imaging in younger women.
False-positive mammograms were more likely in the younger women (odds ratio 1.25; 95% confidence interval [CI]: 1.23-1.26; P<0.001). However, a diagnosis of invasive breast cancer was less likely in that group: OR 0.77; 95% CI: 0.72-0.84; P<0.001)
Looking at breast cancer treatment, the researchers found that younger women with invasive breast cancer were more likely to undergo total mastectomy (41% vs 30.4%), at a cost $1,459 versus $1,012 for a partial mastectomy. Reconstruction, too, was more common in the younger group (35.6% vs 25.4%; $3747 vs $2364).
Commenting on limitations of their study, the authors noted that: (1) all diagnoses and procedures performed may not have been captured in the claims data; (2) some DCIS cases may be have been misclassified as invasive breast cancer, given that the rate of DCIS was lower than expected; and (3) the costs may not be generalizable to other populations because the data were from a single commercial health plan.
For their analysis, researchers at the University of Texas Southwestern used the Dallas Heart Study, a multiethnic population-based cohort aged 30 to 65 years. Participants were included if they had data on self-reported live births and coronary artery calcium (CAC), which had been measured by either aortic wall thickness or computed tomography. Aortic wall thickness was considered positive if it was greater than the 75th percentile reference point for age and gender; CAC was considered positive if it was >10 Agatston units. Sequential multivariable models adjusted for age, traditional cardiovascular risk factors, body mass index, education, income, hormone replacement therapy, oral contraceptives, physical activity, and race were completed.
Among the 1644 women who met the study requirements, the mean age was 45 years and 55% of them were black. Women with 2 to 3 live births were used as a reference. Women who had 4 or more live births were found to have an increased prevalence of elevated CAC (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.28 – 3.65) and aortic wall thickness (OR 1.6, 95% CI 1.04 – 2.41). Women with zero to 1 live births were also found to have increased CAC (OR 1.9, 95% CI 1.16 – 3.03) and aortic wall thickness (OR 1.5, 95% CI 1.05 – 2.09), after adjustment for multiple variables.
The researchers concluded that subclinical coronary and aortic atherosclerosis are associated with live births in a U-shaped relationship. They urged further study to both confirm the association and to find the biologic processes that cause it.
In a multicenter cohort study, routine prenatal screening for aneuploidy with cell-free DNA (cfDNA) testing had a false-positive rate nearly 100 times lower than that for standard screening. Published in The New England Journal of Medicine, the findings-which showed both higher sensitivity and specificity-provide compelling support for use of cfDNA testing in women regardless of age or risk status.
Nearly 19,000 women age 18 and older with singleton pregnancies were represented in the research, which was conducted at 35 international centers. They were assigned to aneuploidy screening at 10 to 14 weeks’ gestation with both standard measurement of nuchal translucency and biochemical analytes, and cfDNA testing. Results of the standard screening were released to the participants, whereas the cfDNA results were blinded. Outcomes at birth were determined based on genetic testing or newborn examination. The primary study outcome was the area under the receiver-operating-characteristic curve (AUC) for trisomy 21. The researchers also evaluated cfDNA testing and standard screening to assess risks of trisomies 18 and 13.
Results reported by the authors were based on data from 15,841 women that were available for analysis. The average maternal age was 30.7 years and the average gestational age at time of testing was 12.5 weeks.
The AUC for trisomy 21 was 0.999 for cfDNA testing and 0.958 for standard screening (P = 0.001). In the cfDNA-testing group, trisomy 21 was detected in all 38 women (100%; 95% confidence interval [CI], 90.7 to 100), versus 30 of 38 women (78.9%; 95% CI, 62.7 to 90.4) in the standard-screening group (P = 0.008). The false-positive rates were 0.06% (95% CI, 0.03 to 0.11) and 5.4% (95% CI, 5.1 to 5.8) for the standard-screening and cfDNA groups, respectively (P < 0.001). Overall, the positive predictive value of cfDNA was 80.9% (95% CI, 66.7 to 90.9) as opposed to 3.4% (95% CI, 2.3 to 4.8) for standard screening (P <0.001).
The researchers concluded that in a large, routine prenatal-screening population, cfDNA testing for trisomy 21 had a lower false-positive rate, higher positive predictive value, and higher sensitivity than the standard screening methods, measurement of nuchal translucency and biochemical analytes. “As emphasized by professional societies,” they noted, however, “the use of cfDNA testing and other genetic tests requires an explanation of the limitations and benefits of prenatal test choices to the patient.”