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Confusion Caused by Conflating "False Positive" and "Overdiagnosis" in Breast Cancer

Posted Nov 27 2009 10:02pm

I have previously discussed some of the issues regarding the recent controversy about mammography screening for women in their 40's (see: Science-Driven Medicine Bumps Up Against Perception of Risk with Mammography; President of the ACP Defends Evidence-Based-Medicine and USPSTF ). Gina Kolata, a highly regarded health reporter for the New York Times, has written one of the best articles to date about how the panel of experts developing the mammography guidelines arrived at their conclusions (see: Behind Cancer Guidelines, Quest for Data ). Having said this, I also should also state that a portion of her article was very confusing, conflating false positive test results with overdiagnosis. Below is an excerpt from it. The Dr. Heidi D. Nelson referred to in this excerpt led a team of researchers in Oregon whose work was the basis for new guidelines on breast cancer screening.

Dr. Nelson’s group drew upon a National Cancer Institute database of eight million mammograms in the United States telling what sort of mammogram — digital or film — the women got, when they got it, and whether they had follow-up tests. Analyzing those data, she concluded that women in their 40s have about a 10 percent chance of a false positive and a 1 percent chance of having a biopsy each time they have a mammogram. While those risks are small, they gain more significance when weighed against the relatively small risk of cancer for women in their 40s — a risk of 1.5 per of 1,000 women. The serious harm, panel members said, is overdiagnosis, finding cancers that are better off not being found. In 2002, when the group last reviewed breast cancer screening studies, the idea of overdiagnosis was not well formed. It has been hard for many people, even scientists, to believe that some cancers start then stop or even regress. But researchers all over the world have been finding overdiagnosis in studies of all sorts of cancers. Dr. Barnett Kramer of the National Institutes of Health, who was not part of the panel, described overdiagnosis as “pure harm” because it means that women are treated with measures like chemotherapy, radiation and surgery for tumors that do not need treating.
A false positive test is one that it erroneously confirms that a patient has a particular disease (i.e., breast cancer). It's a misdiagnosis plain and simple, a misinterpretation. In the case of a breast biopsy report, it's commonly the result of an error on the part of the pathologist interpreting the biopsy. Overdiagnosis, in my opinion, is very different. The various stages of the development of breast cancer constitute a spectrum of disease from a lesion that shows the earliest signs of malignancy to one in which the cells are highly atypical under the microscope and represent an aggressive lesion. One type of overdiagnosis can occur if and when a pathologist tilts in his or her judgment toward a slightly more malignant interpretation on this continuum. This may not be an error on the part of him or her but may rest within the range of correct diagnoses. The pathology report may simply reflect a difference in judgment. The diagnostic criteria may be broad or the experts may not totally agree about them.

However, there is yet another form of overdiagnosis based on the biologic nature of the cancer. Into this category falls those lesions referred to above as "better off not being found." In such cases, for example, all pathologists diagnosing such the lesion might agree that it shows similar morphological criteria of malignancy. However, the lesion may not possess the genes programming it to invade and metastasize in vivo. A competent pathologist would be unable to make this determination because the lesion's morphology would not reveal its true nature. In fact, such a determination might impossible given today's state of knowledge. Lesions of this type should not be biopsied at all because they could lead to the "pure harm" referred to above. Unfortunately and at this time. we don't have a means to determine a priori which breast masses not to biopsy because any diagnosis would constitute overdiagnosis and any treatment would be overtreatment.

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