Breast Cancer Risk After False-Positive Mammography
Breast Cancer Risk After False-Positive Mammography
Background Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests is unknown.
Methods We used data from a long-standing population-based screening mammography program in Copenhagen, Denmark, to determine the long-term risk of breast cancer in women with false-positive tests. The age-adjusted relative risk (RR) of breast cancer for women with a false-positive test compared with women with only negative tests was estimated with Poisson regression, adjusted for age, and stratified by screening round and technology period. All statistical tests were two-sided.
Results A total of 58 003 women, aged 50–69 years, were included in the analysis. Women with negative tests had an absolute cancer rate of 339/100 000 person-years at risk, whereas women with a false-positive test had an absolute rate of 583/100 000 person-years at risk. The adjusted relative risk of breast cancer after a false-positive test was 1.67 (95% confidence interval [CI] 1.45 to 1.88). The relative risk remained statistically significantly increased 6 or more years after the false-positive test, with point estimates varying between 1.58 and 2.30. When stratified by assessment technology phase and using equal follow-up time, the false-positive group from the mid 1990s had a statistically significantly higher risk of breast cancer (RR = 1.65, 95% CI = 1.22 to 2.24) than the group with negative tests, whereas the false-positive group from the early 2000s was not statistically significantly different from the group testing negative.
Conclusions The implementation of new assessment technology coincided with a decrease in the size of excess risk of breast cancer for women with false-positive screening results. However, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening.
In screening mammography, women with positive screening tests typically undergo assessment with triple diagnostics, that is, additional mammograms, ultrasound, palpation, and, if needed, fine needle aspiration cytology or core biopsy. In the majority of instances, the suspicion of malignancy can be ruled out or the final diagnosis of breast cancer can be determined on the basis of these triple diagnostics. In a minority of instances, a surgical biopsy may be needed to reach a conclusion. A high proportion of false-positive tests may result from a wish to uphold high sensitivity, erratic program adherence, technical insufficiency, inadequate interpretive skills, or may lie within the characteristics of the screening population, such as prior benign breast lesions.
Women with false-positive tests manifest suspicious mammographic patterns in their breast tissue including tumor-like masses, suspicious microcalcifications, skin thickening or retraction, recently retracted nipples, distortions, asymmetric densities, or suspicious axillary lymph nodes. One might therefore hypothesize that these women, despite the thorough assessment procedure to exclude malignancies, are at a higher risk of breast cancer than women without these suspicious patterns in their breast tissue. This hypothesis is supported by the overwhelming evidence for an increased risk of breast cancer in women with benign breast lesions. To our knowledge, only three short-term studies have followed the breast cancer risk in women with false-positive screening tests, two from the Netherlands and one from the United Kingdom. In a small Netherlands study from 1988, women with false-positive screening tests had an excess breast cancer risk in the 5 years following screening, whereas the other Netherlands study from 2001 found no excess risk. In the East Anglian screening program, women with false-positive tests had a higher interval cancer rate and a higher detection rate at the subsequent screen than women with negative screening tests. However, the short-term excess risk identified in the 1988 Netherlands study could largely be attributed to misclassification, and the long-term breast cancer risk in women with false-positive tests remains unknown.
Normally, women with false-positive screening tests are referred back to routine screening. To evaluate whether or not this can be considered a safe policy, or whether a closer follow-up should be considered, it is important to know the long-term fate of women with false-positive tests. We used data from a long-standing population-based screening mammography program to determine the long-term risk of breast cancer in women with false-positive screening tests.
Abstract and Introduction
Abstract
Background Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests is unknown.
Methods We used data from a long-standing population-based screening mammography program in Copenhagen, Denmark, to determine the long-term risk of breast cancer in women with false-positive tests. The age-adjusted relative risk (RR) of breast cancer for women with a false-positive test compared with women with only negative tests was estimated with Poisson regression, adjusted for age, and stratified by screening round and technology period. All statistical tests were two-sided.
Results A total of 58 003 women, aged 50–69 years, were included in the analysis. Women with negative tests had an absolute cancer rate of 339/100 000 person-years at risk, whereas women with a false-positive test had an absolute rate of 583/100 000 person-years at risk. The adjusted relative risk of breast cancer after a false-positive test was 1.67 (95% confidence interval [CI] 1.45 to 1.88). The relative risk remained statistically significantly increased 6 or more years after the false-positive test, with point estimates varying between 1.58 and 2.30. When stratified by assessment technology phase and using equal follow-up time, the false-positive group from the mid 1990s had a statistically significantly higher risk of breast cancer (RR = 1.65, 95% CI = 1.22 to 2.24) than the group with negative tests, whereas the false-positive group from the early 2000s was not statistically significantly different from the group testing negative.
Conclusions The implementation of new assessment technology coincided with a decrease in the size of excess risk of breast cancer for women with false-positive screening results. However, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening.
Intrroduction
In screening mammography, women with positive screening tests typically undergo assessment with triple diagnostics, that is, additional mammograms, ultrasound, palpation, and, if needed, fine needle aspiration cytology or core biopsy. In the majority of instances, the suspicion of malignancy can be ruled out or the final diagnosis of breast cancer can be determined on the basis of these triple diagnostics. In a minority of instances, a surgical biopsy may be needed to reach a conclusion. A high proportion of false-positive tests may result from a wish to uphold high sensitivity, erratic program adherence, technical insufficiency, inadequate interpretive skills, or may lie within the characteristics of the screening population, such as prior benign breast lesions.
Women with false-positive tests manifest suspicious mammographic patterns in their breast tissue including tumor-like masses, suspicious microcalcifications, skin thickening or retraction, recently retracted nipples, distortions, asymmetric densities, or suspicious axillary lymph nodes. One might therefore hypothesize that these women, despite the thorough assessment procedure to exclude malignancies, are at a higher risk of breast cancer than women without these suspicious patterns in their breast tissue. This hypothesis is supported by the overwhelming evidence for an increased risk of breast cancer in women with benign breast lesions. To our knowledge, only three short-term studies have followed the breast cancer risk in women with false-positive screening tests, two from the Netherlands and one from the United Kingdom. In a small Netherlands study from 1988, women with false-positive screening tests had an excess breast cancer risk in the 5 years following screening, whereas the other Netherlands study from 2001 found no excess risk. In the East Anglian screening program, women with false-positive tests had a higher interval cancer rate and a higher detection rate at the subsequent screen than women with negative screening tests. However, the short-term excess risk identified in the 1988 Netherlands study could largely be attributed to misclassification, and the long-term breast cancer risk in women with false-positive tests remains unknown.
Normally, women with false-positive screening tests are referred back to routine screening. To evaluate whether or not this can be considered a safe policy, or whether a closer follow-up should be considered, it is important to know the long-term fate of women with false-positive tests. We used data from a long-standing population-based screening mammography program to determine the long-term risk of breast cancer in women with false-positive screening tests.
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