Concordance of allelic imbalance profiles in synchronous and metachronous bilateral breast carcinomas

Bilateral breast cancer (biBC) is a common form of breast cancer; however, it has not been subjected to systematic comparative genetic studies. We allelotyped 28 biBCs on 14 chromosomal arms, addressing 2 lines of questions: (i) does comparison of genetic profiles disclose contralateral metastases misdiagnosed as second primaries? and (R) do shared environmental and host factors drive the development of true biBC along similar genetic routes? Allelotyping provided unambiguous proof for distinct clonality in 23 of 28 cases. In another 4 biBCs, the genotyping data did not exclude the hypothesis of metastatic spread, whereas clinical and histologic data were in favor of bilaterality. Thus the question of clonality remained open only for 1 case, in which the paired tumors shared both histologic features and allelotypes. We conclude that the vast majority if not all biBCs are of independent clonal origin. Next, we assessed the similarity of genetic pathways in distinct categories of biBC. It was assumed that the coexistence of allelic imbalance (AI) in 1 tumor and retention of heterozygosity (N) in the contralateral neoplasm corresponds to the distinct genetic profiles, whereas the remaining combinations (AI/AI or N/N) suggest a match of allelic status for a given polymorphic marker. When these allelic matches were pooled, it turned out that synchronous biBC displayed a significantly higher similarity score than metachronous biBC (64/77 [83%] vs. 1621267 [61%]; p = 0.0003). In addition, an increased similarity of allelic profiles was observed in the premenopausal biBC (76/101 [75%]) compared with postmenopausal cases (111/173 [64%]) or tumor pairs separated by the onset of menopause (39/70 [56%]; p = 0.014). Overall, our data suggest that sharing natural histories of the disease, which is more evident in synchronous and/or premenopausal forms of biBC, may result in a similarity of molecular portraits in bilateral breast tumors. (C) 2002 Wiley-Liss, Inc.