| Title |
Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, October 2015
|
| DOI | 10.1007/s10549-015-3592-z |
| Pubmed ID | |
| Authors |
Jeffrey S. Ross, Siraj M. Ali, Kai Wang, Depinder Khaira, Norma A. Palma, Juliann Chmielecki, Gary A. Palmer, Deborah Morosini, Julia A. Elvin, Sandra V. Fernandez, Vincent A. Miller, Philip J. Stephens, Massimo Cristofanilli |
| Abstract |
Inflammatory breast cancer (IBC) is a distinct clinicopathologic entity that carries a worse prognosis relative to non-IBC breast cancer even when matched for standard biomarkers (ER/PR/HER2). The objective of this study was to identify opportunities for benefit from targeted therapy, which are not currently identifiable in the standard workup for advanced breast cancer. Comprehensive genomic profiling on 53 IBC formalin-fixed paraffin-embedded specimens (mean, 800× + coverage) using the hybrid capture-based FoundationOne assay. Academic and community oncology clinics. From a series of 2208 clinical cases of advanced/refractory invasive breast cancers, 53 cases with IBC were identified. The presence of clinically relevant genomic alterations (CRGA) in IBC and responses to targeted therapies. CRGA were defined as genomic alterations (GA) associated with on label targeted therapies and targeted therapies in mechanism-driven clinical trials. For the 44 IBCs with available biomarker data, 19 (39 %) were ER-/PR-/HER2- (triple-negative breast cancer, TNBC). For patients in which the clinical HER2 status was known, 11 (25 %) were HER2+ with complete (100 %) concordance with ERBB2 (HER2) amplification detected by the CGP assay. The 53 sequenced IBC cases harbored a total of 266 GA with an average of 5.0 GA/tumor (range 1-15). At least one alteration associated with an FDA approved therapy or clinical trial was identified in 51/53 (96 %) of cases with an average of 2.6 CRGA/case. The most frequently altered genes were TP53 (62 %), MYC (32 %), PIK3CA (28 %), ERBB2 (26 %), FGFR1 (17 %), BRCA2 (15 %), and PTEN (15 %). In the TNBC subset of IBC, 8/19 (42 %) showed MYC amplification (median copy number 8X, range 7-20) as compared to 9/32 (28 %) in non-TNBC IBC (median copy number 7X, range 6-21). Comprehensive genomic profiling uncovered a high frequency of GA in IBC with 96 % of cases harboring at least 1 CRGA. The clinical benefit of selected targeted therapies in individual IBC cases suggests that a further study of CGP in IBC is warranted. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 81 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 1% |
| United States | 1 | 1% |
| Unknown | 79 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 17% |
| Researcher | 13 | 16% |
| Other | 9 | 11% |
| Student > Master | 9 | 11% |
| Student > Bachelor | 4 | 5% |
| Other | 16 | 20% |
| Unknown | 16 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 31 | 38% |
| Biochemistry, Genetics and Molecular Biology | 10 | 12% |
| Agricultural and Biological Sciences | 8 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 2% |
| Nursing and Health Professions | 2 | 2% |
| Other | 6 | 7% |
| Unknown | 22 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 October 2015.
All research outputs
#14,699,563
of 22,830,751 outputs
Outputs from Breast Cancer Research and Treatment
#3,167
of 4,659 outputs
Outputs of similar age
#152,088
of 279,097 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#38
of 84 outputs
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