Revisiting multifocal breast cancer: a clonality study of ductal carcinoma using whole exome sequencing.

Multifocal breast cancer (MFBC), ductal type, has been hypothesized to arise by one of two mechanisms: either through intramammary/intralymphatic spread from a single index tumor (MBC-1), or as multiple independent tumors with each focus carrying its corresponding ductal carcinoma in-situ (MBC-2). In order to improve our understanding of MFBC pathogenesis, we employed laser capture microdissection coupled with whole-exome sequencing to study clonal origin in MFBC. We selected three cases of MBC-1 (C1 to C3) and MBC-2 (C4 to C6) and analyzed three foci from each case.

Microglandular adenosis is an advanced precursor breast lesion with evidence of molecular progression to matrix-producing metaplastic carcinoma.

Microglandular adenosis (MGA) is a rare breast lesion reported to be associated with invasive carcinoma in up to 20% to 30% of cases and has been proposed as a nonobligate precursor to basal-like breast cancers. We identified a case of matrix-producing metaplastic carcinoma with morphologic and immunohistochemical evidence of progression from MGA to atypical MGA, carcinoma in situ, and invasive carcinoma. We performed whole-exome sequencing of each component (MGA, atypical MGA, carcinoma in situ, and cancer) to characterize the mutational landscape of these foci.