Women with risk factors for breast cancer were more likely to be recalled for additional imaging and biopsy after screening mammography when they did not have breast cancer. Unfortunately, this increase in recall did not result in an increased probability of detecting cancer when it was present. Moreover, although the PPV trended towards being higher among women with risk factors, the magnitude of this increase was not as large as we would expect due to the actual increased cancer rate noted among these women.
Our findings suggest that radiologists' interpretations may be influenced by information about patient risk available to them at the time of the mammogram. Availability of risk factor information may improve performance among women with no risk factors, as these women were less likely to have a false-positive examination with no change in the probability of detecting cancer. False-positive rates for low risk women are within the recommended U.S. guidelines of <10% (10
). In contrast, for every 1,000 women with three risk factors screened, 34 more women were recalled for additional imaging compared to those with no risk factors, and 10 more women were recommended for biopsy. Unfortunately, this increase in work-up did not correspond to an increase in detecting cancer when it was present.
It is possible that radiologists are overly cautious about interpreting mammographic findings among women with risk factors, because they overestimate these women's pre-test probability of cancer. Indeed, in one study of these same radiologists, 96% overestimated an individual woman's 5- year risk of a diagnosis of breast cancer, particularly those with risk factors such as family history of breast cancer and prior biopsy (15
). This suggests that radiologists may be over influenced by some risk factors when they are deciding whether or not to recall women for additional work up or are considering whether or not to biopsy a possible abnormality.
While observational studies have shown that mammography performed on women currently using postmenopausal hormone therapy (HT) have higher false positive rates (8
) and lower sensitivity (8
) it is not clear if this is completely caused by HT's effect on breast density or if radiologists are being influenced by the knowledge of HT use, or both. In our study, we adjusted our analyses for radiologists' interpretation of breast density. Thus, our findings should not be affected by breast density patterns. The increased recall and biopsy recommendation rates may be appropriate if true abnormalities are visually apparent on the exam.
It is possible that women with risk factors have different breast architecture and lesions visible on their exams compared to women with no risk factors. For example, women taking conjugated equine estrogen have been shown to be at increased risk of benign proliferative breast disease (16
) and women with a family history of breast cancer were shown to have an increased risk of biopsy confirmed benign breast disease (17
). In another study, Berg and colleagues found no increased risk for breast cancer associated with radial scar beyond that of proliferative disease without atypia that occurs in the general population (23
). Another study (19
) examined multiple benign breast pathology (non-proliferative, proliferative, or proliferative with atypia) to address the issue of the contribution of concurrent multiple lesions on breast cancer risk. They found that >70% had more than one type of benign lesion and that multiple benign lesions and patient age were associated with increased risk of subsequent breast cancer. In yet another study(25), investigators found that among women with atypical hyperplasia, multiple foci of atypia and presence of histologic calcifications appears to indicate very high risk (> 50% risk at 20 years), but that a positive family history does not further increase risk in women with atypia. These studies suggest that visual distortions possibly associated with risk are likely present and may need work-up. However, more research is needed to determine how best to provide surveillance to women with multiple risk factors for breast cancer.
We know of only a few studies that have examined the influence of clinical information on the accuracy of mammography, and most of these focused on diagnostic rather than screening mammography (2
) and have produced conflicting results (20
). Prior studies that evaluated the influence of risk factors on interpretive performance had several weaknesses, including the small number of radiologists studied (≤10). Prior studies also measured performance using test sets, which may not replicate actual practice(2
Our study had several strengths in contrast to the published literature. We examined mammography performance data from actual clinical practice in three geographically distinct regions in the US as opposed to evaluating performance using test sets of mammograms. In addition, because of the large number of radiologists and mammograms included, our findings are likely more stable then results from test sets. Another important strength of our study is that we had the ability to perform analyses that accounted for radiologists' characteristics previously shown to influence performance in other studies, such as radiologist age, number of years interpreting mammograms, and annual interpretive volume (7
, 28). We, therefore, had the unique opportunity to conduct within-radiologist comparisons by applying conditional logistic regression models. This statistical technique can be used to account for all between radiologist differences including differences in case-mix (14
). Results are therefore interpreted on the mammogram level and measure the effect of changing the number of clinical risk factors for an individual radiologist's performance, removing the potential effect of between radiologist differences. This is a key improvement from most analyses conducted in this area, since previous applied methods did not separate the between and within-in radiologist effects. Between radiologist differences may overshadow any within-in radiologist relationships that are of actual interest. For example, the between effect for changing number of clinical risk factors would be estimating whether radiologists who interpret mammograms more often on higher risk women have a different interpretative performance then those who typically interpret mammograms on lower risk women. This could occur if women with more risk factors were more likely to obtain mammograms at particular facilities, such as academic facilities, which have different baseline interpretive performance rates (24
). One could attempt to control for confounders through adjustment, but it is difficult to identify and accurately measure all possible confounders. Using conditional logistic regression assures that case-mix is being fully adjusted for without making such strong assumptions and therefore you are able to easily and robustly estimate pure within radiologist effects.
Our study also had some limitations. We did not examine whether the radiologists actually used the risk factor information at the time of the mammogram interpretation; rather we only looked at whether the risk factors were reported at the screening examination. A follow-up study should identify whether and how radiologists use clinical history in screening mammography interpretation, as this may be an area in which the performance can be improved. In addition, we cannot determine whether the increased recall and biopsy rates observed for high risk women were appropriate, given that these women may be at increased risk of benign breast disease that requires additional work-up to rule-out cancer.
In conclusion, our large multi-center study found that radiologists are less likely to recall women who have no risk factors for breast cancer, reducing the number of false-positive examinations in these women without increasing the probability of missing cancers. However, our findings also suggest that radiologists may be over using clinical history about women's risk factors in their recall of more women with risk factors without increasing the probability of detecting cancer, particularly for women who are currently using HT and/or have had a previous biopsy. Alternatively, this increased recall may be appropriate given that the clinical risk factors we studied are associated with an increased risk of benign breast disease. Women with multiple risk factors for breast cancer should be informed that they are at elevated risk of being recalled for additional follow-up and biopsy following a screening mammography examination even when breast cancer is not present.