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Why We Need to Do Better
For a further striking example of the need for greater precision in the realm of analysis of breast cancer, consider a 2015 study published in the Journal of the American Medical Association suggesting that biopsies are less than reliable for identifying subtle tissue abnormalities in ambiguous cases.[vi] Although separate groups of experts and working pathologists agreed in identifying unambiguously healthy tissue and unambiguously cancerous tissue on slides that were provided to them, there was much less agreement in borderline cases where diagnoses such as ductal carcinoma in situ (DCIS) or atypical ductal hyperplasia (atypia) were likely to be made. Specifically, there was 84 percent agreement in diagnoses for DCIS and only 48 percent agreement in diagnoses for atypia.
What accounts for the ambiguity in diagnosis between the experts and the pathologists? The differences in diagnoses can be traced to the “gray zone” that sometimes exists between normal and malignant results. Although both groups of individuals who examined the slides in this study have substantial experience analyzing biopsy results, there is still a measure of subjective judgment involved. It is important to understand that the morphological criteria and definition of cancer has not changed for decades. It was inevitable that in the absence of more detailed analysis, opinions among the two groups regarding specific slides would vary. Overall, the disparity is unsettling, as it may result in either the overtreatment or the undertreatment of women with newly diagnosed—and potentially inappropriately diagnosed—breast lesions.
This naturally leads us to ponder the major challenges in diagnosing the potential for breast cancer at the pre-malignant stages. There is interest in both the medical and lay community in the earlier diagnosis of breast cancer and other malignancies as well. However, a more sophisticated discussion would really be in everyone’s best interest. Identifying more tumors as cancers when we don’t understand their clinical significance has the potential to result in significant overtreatment.
It is more important that we understand the metastatic potential of a tumor rather than just labeling a lesion a cancer. A tumor that has little metastatic potential is very different from a lesion with significant metastatic potential. The diagnosis of breast cancer usually changes and negatively impacts a patient’s life. Molecular and epigenetic-based diagnostic tests have the potential to deliver more accurate and personalized information that should lead to more effective treatment options.
The misinterpretation of biopsies can lead women to have surgery and other treatments they don’t need. As the disparity in diagnoses in the JAMA study reveal, relying on traditional approaches to diagnosing cancer can lead to clinical mistakes, especially in pre-malignant cases. And if experts can’t even agree on what cancer looks like under the microscope, they surely can’t understand the underlying biology—and whether a specific cancer will become invasive. This situation also highlights the importance of next-generation diagnostics. Giving patients more refined knowledge of the specific challenge they face is crucial, because once you tell them they “have cancer,” you’ve frightened them and changed their life. Next-generation diagnostics could eventually lead to more targeted therapies for specific subsets of cancer patients, as well as to increasing savings for hospitals and patients. On a broader scale, next-gen diagnostics could lead to more precise diagnosis to other cancers.
Better diagnostic tests will accelerate the delivery of personalized cancer therapy. Next-generation tests are moving away from a morphological approach to diagnosis to a more molecular-based approach, and this should result in better outcomes for patients and significant savings for the healthcare system. Cancer is complicated and “messy,” and relying on traditional criteria to establish this diagnosis potentially leads to incorrect approaches to the needs of individual patients.
