Pathogenic Germline Variants in Patients With Metaplastic Breast Cancer
Kaitlin Demarest1, Arravinth Anantharajah1, Kara N Maxwell1,2,3
1Basser Center for BRCA, University of Pennsylvania, Philadelphia.
JAMA Network Open
|February 18, 2025
Summary
Pathogenic germline variants (PGVs) are common in metaplastic breast cancer (MpBC), with BRCA1 being the most frequent. Germline genetic testing is highly effective for identifying these variants in MpBC patients.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Metaplastic breast cancer (MpBC) is a rare and aggressive breast cancer subtype.
- Limited data exist on pathogenic germline variants (PGVs) in breast cancer susceptibility genes within the MpBC population.
- Understanding PGV prevalence is crucial for risk assessment and treatment strategies.
Purpose of the Study:
- To determine the frequency and spectrum of PGVs in breast cancer genes among patients diagnosed with MpBC.
- To assess the clinical utility of germline genetic testing in this patient cohort.
Main Methods:
- A retrospective cohort study was conducted on 272 patients with confirmed MpBC diagnosed between January 2010 and May 2023.
- Electronic medical records were reviewed for demographic, clinicopathologic, and germline genetic testing data.
- Germline variant status was confirmed by genetic counselors and physicians; MpBC diagnosis and subtype by a pathologist.
Main Results:
- Of 143 patients who underwent germline genetic testing, 16.8% (24/143) harbored a PGV in a breast cancer susceptibility gene.
- The most commonly identified PGVs were in BRCA1 (17 patients) and BRCA2 (5 patients).
- Patients with PGVs were diagnosed at a younger age compared to those with sporadic MpBC, with no significant differences in other clinicopathologic features.
Conclusions:
- A significant proportion of patients with MpBC carry PGVs in breast cancer susceptibility genes, particularly BRCA1.
- Germline genetic testing demonstrates high yield in MpBC patients, identifying many who meet current testing criteria.
- These findings support the routine consideration of germline genetic testing for individuals with MpBC.
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