Article

DCIS: An example of why screening and disease classification go hand-in-hand

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If we are screening for any disease, we have to have a plan for everything that is detected as abnormal. When mammographic screening became widespread in the mid '80s, there was a rapid rise in the number of cases of "pre-invasive" cancer, known as ductal carcinoma in situ, because these lesions tend to calcify and lead to tell-tale specs on X-ray examinations. DCIS does not spread, and many individuals may never have any consequences of the lesions, even if it was never detected. Despite that, when these are found, surgery to remove all the DCIS is the generally accepted treatment because some of these are associated with the more dangerous form of invasive cancer or can recur after surgery--either as DCIS or invasive cancers, and invasive cancers can spread, so minimizing these recurrences are important.In fact, even after surgery, radiation and tamoxifen are sometimes used to lower the chance of any recurrence. Like many other screening efforts, we clearly overtreat those diagnosed with the disease because we have no way of predicting which DCIS cases are dangerous, and which ones can be left alone or treated with minimal surgery only. There are several factors that give us some clues about more aggressive tendencies, such as the overall size, nuclear grade of the cells, or how the cells are organized (called histology). But these are not selective enough to spare most patients from treatment they may not need, or on the other hand, to falsely reassure us that conservative management will be enough. Of course, there will never be a test that is fully accurate in this regard, but have we come closer with a series of markers that are all linked to early aberrant growth signals? A recent report from researchers at the University of California at San Francisco looked at a large population-based series of DCIS with eight years of average follow-up time, a rather short timeframe given the long window of recurrence risk. They found that these markers did not individually help discriminate, but when they were combined, they identified a "lower-risk" group, about half of the overall number of cases, that had a 2 percent to 4 percent risk of local recurrence, an intermediate group at 8 percent, and a higher-risk group at 14 percent. However, the accompanying editorial sounded a cautionary note that this scale needs to be validated in another group of patients. We are all now acutely aware of part of the mammographic screening debate--that is, how to handle low-risk findings that inevitably will come up. The bottom line is if we can avoid "overtreatment," screening becomes a more effective and acceptable tool. Whether the ultimate test will just be these few marker indicated in this report, or something more complicated, like gene profiling, it will take special efforts to tap into larger DCIS cohorts in order to validate, and also to commercialize and enact quality-control for such an assay. While this test is not ready for routine use, it is a step in the right direction of more effectively triaging DCIS so that the "punishment fits the crime."

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