lunes, 9 de julio de 2018

Clinicopathologic Characterization of Breast Carcinomas in Patients with Non-BRCA Germline Mutations: Results from a Single Institution's High Risk... - PubMed - NCBI

2018 Jun 26. pii: S0046-8177(18)30238-7. doi: 10.1016/j.humpath.2018.06.024. [Epub ahead of print]

Clinicopathologic Characterization of Breast Carcinomas in Patients with Non-BRCA Germline Mutations: Results from a Single Institution's High Risk Population.

Meiss AE1, Thomas M2, Modesitt SC3, Ring KL3, Atkins KA4, Mills AM5.

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Abstract

As multigene panel testing for hereditary cancer syndromes becomes commonplace, germline mutations in genes other than BRCA1/2 are increasingly identified in breast cancer patients. While histopathologic features of BRCA-mutated breast cancers have been well-characterized, less is known about non-BRCA-related hereditary cancers. We herein investigate the clinicopathologic characteristics of breast cancers in women with non-BRCA germline mutations. Out of 612 women who underwent germline testing, 16 (2.6%) of women with 18 cancers had mutations in non-BRCA genes: ATM, CHEK2, PALB2, TP53, BMPR1A, BRIP1, MUTYH, and RAD50. An additional two cancers were identified in a woman with a diagnosis of Bloom syndrome (BLM mutation) who was not germline tested. Average age at diagnosis was 50 (range: 27-77), and 65% had no personal cancer history. The majority (79%) of tumors were grade 1-2. 35% were either lobular or ductal with lobular features. Stromal responses varied from absent to desmoplastic to sclerotic. 69% of cases had an in situ component. With the exception of a brisk lymphocytic response in BLM and TP53-mutated cancers, lymphocytic infiltration was mild or absent. In summary, the majority of non-BRCA-related hereditary breast cancers represent the patient's sentinel malignancy. Lobular features were seen in a subset and high-grade, immunogenic carcinomas were uncommon except in the setting of BLM and TP53 mutations. Overall, these findings demonstrate a range of involved genes in non-BRCA mutation carriers with breast cancer and histopathologic heterogeneity in the associated cancers, arguing against use of histomorphology to inform panel testing algorithms.