Limitations
SECONDARY, BREAST CANCER
Our study has limitations. First, a substantial proportion of patients included in the CALGB 40601 and PAMELA trials received trastuzumab combined with lapatinib, a dual treatment used in the metastatic setting but not approved for early-stage ERBB2/HER2-positive breast cancer. Moreover, the PAMELA trial differed from the CALGB 40601 trial in that patients received only anti-ERBB2/HER2 therapy before surgery, without chemotherapy. Second, although EFS was a key secondary end point of the CALGB 40601 trial, the trial was not powered for long-term outcomes, so EFS prediction modeling should be interpreted with caution. Third, even when scored as a continuous variable, the proportion of TILs (ie, 0% to 100%) follows a semiquantitative pattern, with increments of 5% to 10%, and thus is not a true continuous variable like iGESs. However, when TILs were divided into high vs low levels based on multiple prespecified cutoffs, their ability to predict response and survival was lower than that of multiple B-cell–related signatures. Finally, we performed numerous statistical predictions simultaneously by building 1 model for each immune biomarker to predict pCR and EFS. To control type I error, we adjusted the models’ 