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Updated: Jul 11, 2025
08:16
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
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Nonlobular Invasive Breast Carcinomas with Biallelic Pathogenic CDH1 Somatic Alterations: A Histologic,
Fatemeh Derakhshan1, Arnaud Da Cruz Paula2, Pier Selenica3
1Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York.
Summary
Biallelic CDH1 alterations, a hallmark of invasive lobular carcinoma, are exceptionally rare in nonlobular breast cancers. These rare cases often present as invasive ductal carcinomas with specific features and share genomic similarities with luminal B breast cancers.
Area of Science:
- Genomic analysis of breast cancer subtypes
- Molecular pathology of breast carcinoma
Background:
- CDH1 gene mutations and E-cadherin loss are characteristic of invasive lobular carcinoma (ILC).
- Biallelic CDH1 alterations are infrequently observed in nonlobular breast carcinomas (NL-BCs).
Purpose of the Study:
- To investigate the clinicopathologic features of NL-BCs with biallelic CDH1 genetic alterations.
- To identify the spectrum of genetic alterations in these rare NL-BCs.
- To compare the genomic profiles of these NL-BCs with ILCs and invasive ductal carcinomas (IDCs).
Main Methods:
- Analysis of 5842 breast cancers using clinical tumor-normal sequencing with an FDA-cleared multigene panel.
- Identification of cases with biallelic CDH1 pathogenic/likely pathogenic somatic mutations and absence of lobular features.
- Comparative genomic profiling of identified NL-BCs against ILCs and IDCs.
Main Results:
- Only 7 out of 5842 (0.11%) breast cancers exhibited biallelic CDH1 alterations without lobular features.
- These NL-BCs included various invasive ductal carcinoma subtypes and were predominantly ER-positive/HER2-negative.
- Genomic analysis revealed recurrent alterations in TP53 and PIK3CA, and a lower frequency of GATA3 mutations compared to wild-type IDC-NSTs.
Conclusions:
- NL-BCs with biallelic CDH1 alterations are exceedingly rare, often presenting as IDCs with special histologic features.
- These tumors exhibit genomic profiles similar to luminal B ER-positive breast cancers.
- The findings contribute to understanding the molecular heterogeneity of breast cancer beyond the typical lobular histology.
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