To the Editor In his recent editorial, Dr Hayes correctly noted that “analytical validity and clinical utility” are needed for the adoption of a tumor biomarker test into clinical care.1 However, proving analytical validity with correlative or concordance studies is largely irrelevant without first proving clinical utility.
After adjuvant studies of trastuzumab demonstrated a remarkable roughly 40% reduction in human epidermal growth factor receptor 2 (HER2)-positive breast cancer recurrence risk, it was estimated that there must be patients who would have benefited from anti-HER2 therapy but were ineligible for the key adjuvant studies based on the definitions of HER2 positivity for entry into those trials. Therefore, in 2013 an expert American Society of Clinical Oncology/College of American Pathologists panel expanded the guideline to include additional definitions of HER2 positivity (eg, apparent polysomy causing increased HER2 copy number) so that the “the right patient receives the right treatment.”2(p4000) The authors recommended clinical trials to prove efficacy for patients receiving anti-HER2 therapies based on having tumors deemed positive based only on 1 or more of the new definitions. Since that time, there have been numerous concordance or correlative studies aimed at verifying analytical validity.