The article “Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of HERA Trial,” by Loi et al1 in this issue of JAMA Oncology entices the reader with the conclusion that certain human epidermal growth factor receptor-2 positive (HER2+, now known as ERBB2) breast cancers that are also estrogen receptor positive (ER+) “derive significantly less benefit from adjuvant trastuzumab after chemotherapy.”1 The phrase, “significantly less,” has special connotation for scientists and clinicians trained to disregard findings that do not meet statistical significance. This concluding statement questions whether trastuzumab is of value in the patients we have come to call “triple positive” (ER+, progesterone receptor positive, and HER2+), especially if ER expression is high and if concurrently the fluorescent in situ hybridization (FISH) ratio determining HER2 positivity is low (≥2 to <5). Based on this article, should we rethink our use of trastuzumab in these patients?