Breast cancer in Lynch Syndrome patients: genomic and pathologic evidence in support of a potential causal relationship

The association of Lynch syndrome (LS) and breast cancer has been a widely debated and controversial topic in past decades. Here we characterized the pathologic and genomic features of breast cancers (BCs) occurring in LS patients and investigated whether these breast cancers are casually linked to...

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Published in:Clinical cancer research 2021-10, Vol.28 (2), p.404-413
Main Authors: Schwartz, Christopher J., da Silva, Edaise M., Marra, Antonio, Gazzo, Andrea M., Selenica, Pier, Rai, Vikas K., Mandelker, Diana, Pareja, Fresia, Misyura, Maksym, D’Alfonso, Timothy M., Brogi, Edi, Drullinsky, Pamela, Razavi, Pedram, Robson, Mark E., Drago, Joshua Z., Wen, Hannah Y., Zhang, Liying, Weigelt, Britta, Shia, Jinru, Reis-Filho, Jorge S., Zhang, Hong
Format: Article
Language:English
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Summary:The association of Lynch syndrome (LS) and breast cancer has been a widely debated and controversial topic in past decades. Here we characterized the pathologic and genomic features of breast cancers (BCs) occurring in LS patients and investigated whether these breast cancers are casually linked to the mismatch repair deficiency (MMRd) that defines LS-related cancers. Out of 20,110 cancer patients who underwent multigene genetic testing on tumor and matched normal DNA samples, 272 LS individuals were identified, 13 of whom had primary breast cancers. Five of these 13 BCs displayed MMRd by immunohistochemistry and/or dominant MSI-related mutational signatures as defined by tumor-normal sequencing. One patient with widely metastatic ER positive/HER2 negative MMRd BC achieved a robust and durable response upon treatment with anti-PD1 immunotherapy. Although LS-associated BCs are rare, this study highlights a subset that are etiologically linked to underlying MMRd and may be candidates for immunotherapy.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-21-2027