deviation estimates were … acceptable as they are <5% of the … reportable range” (page 24 of Supplementary Data). Although this suggests the assay has potential for technical validation, data on assay reproducibility, particularly with respect to diagnosis of patients with “borderline” results is not presented, making it difficult to be confident that the assay robustly stratifies patients, either at central or peripheral hospital laboratories. Experience with single markers [eg, HER2 (6,7)] suggests these are critical components of technical validation, and in our opinion this is as important for multiparameter tests as it is for “simple” single marker assays. Accuracy is more challenging to demonstrate, particularly when a broad phenotypic assay is applied, but evidence shows this challenge can be addressed with appropriately designed studies (8–10). EGAPP (5) guidelines state that “convincing” evidence for analytical validity requires “studies that provide confident estimates of analytic sensitivity and specificity” using representative samples, particularly addressing challenging cases. Such data may be available, and, if so, should be published to demonstrate technical validity of the DNA-damage response deficiency (DDRD) assay. The authors present several analyses supporting utility of the DDRD signature to predict outcome after chemotherapy in both neoadjuvant and adjuvant settings, They show convincingly that the DDRD signature is associated with either pathological complete response or relapse after chemotherapy but not in patients who did not receive chemotherapy. They used publically available and institutional cohorts, including three neoadjuvant cohorts (n = 51, 66, and 86 patients, respectively) treated with fluorouracil, epirubicin, and cyclophosphamide (FEC)/fluorouracil, doxorubicin, and cyclophosphamide (FAC), and four adjuvant cohorts, of which three were untreated and one (n = 191 patients) was treated “historically” with FAC. The data support a role for the DDRD signature in prediction of residual risk after chemotherapy, but do they clinically validate the formalin-fixed paraffin-embedded DDRD assay for anthracycline/cyclophosphamide chemotherapy response as claimed? We argue that, although these data are interesting and part of a pathway leading to clinical validation, they rep