As discussed in previous paragraphs, seminal studies showed that positivity is generally lower than 30% before starting primary systemic therapy or before surgical intervention, but the sensitivity of the enrichment method can substantially increase when analyzing large volumes of blood, or when using antigen-independent size-based selection, or when screening the white blood cell fraction for the expression of epithelial and breast-cancer associated markers and the presence of HER2 amplification, reaching positivity higher than 70%. This evidence concerns the gene ERBB2 and breast carcinoma.