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October 20, 2004


JAMA. 2004;292(15):1817-1818. doi:10.1001/jama.292.15.1818-a

In Reply: Drs Tubbs and Hicks argue that because of our deviation from the FDA-approved guidelines our test “becomes an in-house validated assay.” We would first point out that the guidelines themselves have limitations, of which the FDA itself appears aware. In a recent briefing document, the FDA submitted that “the clinical benefit of trastuzumab was primarily seen in patients whose tumors were scored as IHC 3+.”1 But the FDA included the 2+ subgroup with the 3+ group for consideration for trastuzumab therapy. Subsequently, pivotal studies like that of Tubbs et al2 showed that most of the 2+ scores by IHC are essentially false-positive. This supports the FDA Drug Advisory Committee’s initial predictions that the 2+ score may not be associated with the desired response to trastuzumab. Nonetheless, the FDA has not eliminated the 2+ score result as a requirement for eligibility to trastuzumab treatment despite evidence to the contrary.