To the Editor: Dr Yaziji and colleagues1 compared immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests for overexpression of human epidermal growth factor receptor-2 (HER-2). Based on the inconvenience and higher cost of FISH, they concluded that HER-2 determination was most "efficient" by using IHC, with FISH performed for tumors with an IHC score of 2+. FISH was not recommended in tumors with an IHC score of 3+. Although I agree that FISH should be performed if the IHC score is 2+, the omission of confirmatory FISH when the IHC score is 3+ could lead to several adverse financial and ethical consequences.
First, HER-2 status determines if a woman should receive trastuzumab, an antibody specifically targeting tumor cells overexpressing HER-2 gene. The FISH test is currently the most predictive of tumor response.2 Indeed, Yaziji et al found 8.4% of the tumors with an IHC score of 3+ were, in fact, FISH-negative. Treating these women with trastuzumab would likely render the strategy cost-ineffective, as trastuzumab costs about $2700 per month plus infusion and premedication costs.3 Furthermore, the duration of treatment is life-long for metastatic breast cancer. Clearly, the cost of FISH ($140 per test) can easily be offset by savings from avoiding unnecessary trastuzumab treatment. In fact, a recent analysis considering different testing strategies, treatments, and life-gains also shows that confirmatory FISH for cancers with an IHC score of 2+ or 3+ is more cost-effective than is confirmatory FISH only for cancers with an IHC score of 2+.4
Second, trastuzumab is associated with a number of adverse effects, including cardiotoxicity and infusion-related anaphylaxis.2 Before subjecting a patient to the risk of such toxicity, clinicians should know with the best of their ability that the treatment is not futile.
Third, because HER-2 overexpression portends aggressive disease and poor survival, it is a common clinical practice to use HER-2 status to make a decision on adjuvant cytotoxic chemotherapy. HER-2 overexpression also affects the decision to give patients anthracyclines in early stages of breast cancer.5 The importance of correct HER-2 status cannot be overestimated.
I believe that the authors' algorithm should be modified to recommend confirmatory FISH for cancers with an IHC score of 3+ before important clinical decisions are made.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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