Clinically advanced and metastatic pure mucinous carcinoma of the breast: a comprehensive genomic profiling study
| Autor: | Ann Boguniewicz, James Suh, Depinder Khaira, Vincent A. Miller, Philip J. Stephens, Sahar Nozad, Jo-Anne Vergilio, Jeffrey S. Ross, Julia A. Elvin, Kai Wang, Adrienne Johnson, Siraj M. Ali |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty medicine.medical_treatment STK11 Breast Neoplasms Targeted therapy 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine medicine Mucinous carcinoma Humans Molecular Targeted Therapy Mucinous Breast Carcinoma Aged business.industry Cancer High-Throughput Nucleotide Sequencing Genomics Amplicon Middle Aged medicine.disease Adenocarcinoma Mucinous 030104 developmental biology 030220 oncology & carcinogenesis Mutation Immunohistochemistry Female business |
| Zdroj: | Breast cancer research and treatment. 155(2) |
| ISSN: | 1573-7217 |
| Popis: | Pure mucinous breast carcinoma (pmucBC) is a distinctive variant of breast cancer (BC) featuring an excellent overall prognosis. However, on rare occasions, pmucBC pursues an aggressive clinical course. We queried whether comprehensive genomic profiling (CGP) would uncover clinically relevant genomic alterations (CRGA) that could lead to targeted therapy treatment for patients with an advanced and metastatic form of pmucBC. From a series of 51,238 total cancer samples, which included 5605 cases of clinically advanced BC and 22 cases of stage IV pmucBC, DNA was extracted from 40 microns of FFPE sections. Comprehensive genomic profiling was performed using a hybrid-capture, adaptor ligation-based next generation sequencing assay to a mean coverage depth of 564X. The results were analyzed for all classes of genomic alterations (GA) including base substitutions, insertions and deletions, select rearrangements, and copy number changes. Clinically relevant genomic alterations were defined as those indicating possible treatment with anti-cancer drugs on the market or in registered clinical trials. Samples were obtained from breast (11), lymph nodes (3), chest wall (2), liver (2), soft tissue (2), bone (1), and pleura (1). The median age of the 22 pmucBC patients was 57 years (range 32–79 years). Three pmucBCs were grade 1, 17 were grade 2, and 2 were grade 3. Twenty-one (95 %) pmucBC were ER+, 18 (82 %) were PR+, and 3 (14 %) were HER2+ by IHC and/or FISH. A total of 132 GA were identified (6.0 GA per tumor), including 53 CRGA, for a mean of 2.4 GA per tumor. Amplification of FGFR1 or ZNF703, located within the same amplicon, was found in 8 of 22 cases (36 %). This enrichment of FGFR1 amplification in 36 % of pmucBC versus 11 % of non-mucinous ER+ BC (601 cases) was significant (p |
| Databáze: | OpenAIRE |
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