In a subsequent prospective validation in 259 case-control pairs with and without distant recurrence from a population-based cohort, TMEM doorway density was likewise associated with an increased risk of distant metastasis in the subset of those with hormone receptor-positive, HER2-negative breast cancer (P trend = 0.004), but not in triple-negative or HER2-positive breast cancer. This evidence concerns the gene ERBB2 and breast cancer.