Histopathologic features of breast cancer in Li–Fraumeni syndrome



Breast cancer is the most common malignancy in female patients with Li–Fraumeni syndrome (LFS), a rare autosomal dominant hereditary syndrome characterized by germline TP53 mutations. Recent studies have shown that the majority of these tumors are estrogen receptor (ER) positive with frequent HER2 co-expression. However, the morphologic features of these tumors have not been as well studied as other germline-associated breast cancers. We evaluated the pathologic features of 27 invasive and in situ carcinomas from patients with known germline TP53 mutations collected through the Li–Fraumeni Consortium. Overall, 60% of cases were HER2 positive and 44% showed ER co-expression. Most DCIS was high nuclear grade with central necrosis and associated periductal fibrosis and lymphocytic response. Invasive carcinomas were mostly of ductal type (NOS), modified Scarff–Bloom–Richardson (mSBR) high grade, with marked nuclear atypia and high mitotic rate. Prominent tumor infiltrating lymphocytes, syncytial growth pattern, or pushing borders were not seen in these tumors. High p53 IHC expression was seen in tumors from individuals with germline TP53 missense mutations whereas little or no protein expression (<1% nuclear expression, null pattern) was seen in tumors from carriers of non-missense mutations. In this study, we report in detail the morphologic features of invasive and in situ carcinomas in LFS. We found that these tumors share features with cancers harboring somatic TP53 mutations but are distinct from BRCA-associated breast cancers.

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Fig. 1: Morphologic features of invasive carcinomas.
Fig. 2: Example of invasive carcinoma.
Fig. 3: Morphologic features of ductal carcinoma in situ (DCIS).
Fig. 4: Example of ductal carcinoma in situ (DCIS).


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We thank the following: Li–Fraumeni Syndrome Consortium members for the contribution of cases for this study: Mark Robson, Jeffrey N. Weitzel, Judith Balmana, Stephen B. Gruber, James M. Ford, David Euhus, Melinda Telli, and Stephen M. Pochebit.

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Correspondence to M. Gabriela Kuba.

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Conflict of interest

DAD consults for Novartis and is on the Advisory Board for Oncology Analytics, Inc. JEG receives research support from Myriad Genetics, Ambry Genetics, Invitae Genetics, is leading two clinical trials for Astra-Zeneca, consults for Helix Genetics, is on the Scientific Advisory Board of Konica Minolta, and has received speaker’s honorarium from Clinical Care Options, LLC. The other authors declare no conflict of interest.

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Kuba, M.G., Lester, S.C., Bowman, T. et al. Histopathologic features of breast cancer in Li–Fraumeni syndrome. Mod Pathol (2020). https://doi.org/10.1038/s41379-020-0610-4

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