The hypothesis that even heterozygotic loss of BRCA1 may allow for an increase in mitogenic signaling and thereby convey a growth advantage to MECs with genetic instability is further supported by the fact that BRCA1 mutation carriers have a strikingly high frequency of atypical ductal hyperplasia (38% in BRCA1 carriers versus 4% in control tissues) and ductal carcinoma in situ (13% in BRCA1 carriers versus none in control tissues) [46], which most often is negative for ER and positive for EGFR [47]. This evidence concerns the gene ESR1 and ductal breast carcinoma in situ.