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Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations.
Breast Cancer Res Treat. 2015 Nov; 154(1):155-62.BC

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.

Authors+Show Affiliations

Foundation Medicine, Cambridge, MA, USA. rossj@mail.amc.edu. Department of Pathology, Albany Medical College, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA. rossj@mail.amc.edu.Foundation Medicine, Cambridge, MA, USA. sali@foundationmedicine.com.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Thomas Jefferson University Cancer Center, Philadelphia, PA, USA.Foundation Medicine, Cambridge, MA, USA.Foundation Medicine, Cambridge, MA, USA.Thomas Jefferson University Cancer Center, Philadelphia, PA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26458824

Citation

Ross, Jeffrey S., et al. "Comprehensive Genomic Profiling of Inflammatory Breast Cancer Cases Reveals a High Frequency of Clinically Relevant Genomic Alterations." Breast Cancer Research and Treatment, vol. 154, no. 1, 2015, pp. 155-62.
Ross JS, Ali SM, Wang K, et al. Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations. Breast Cancer Res Treat. 2015;154(1):155-62.
Ross, J. S., Ali, S. M., Wang, K., Khaira, D., Palma, N. A., Chmielecki, J., Palmer, G. A., Morosini, D., Elvin, J. A., Fernandez, S. V., Miller, V. A., Stephens, P. J., & Cristofanilli, M. (2015). Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations. Breast Cancer Research and Treatment, 154(1), 155-62. https://doi.org/10.1007/s10549-015-3592-z
Ross JS, et al. Comprehensive Genomic Profiling of Inflammatory Breast Cancer Cases Reveals a High Frequency of Clinically Relevant Genomic Alterations. Breast Cancer Res Treat. 2015;154(1):155-62. PubMed PMID: 26458824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations. AU - Ross,Jeffrey S, AU - Ali,Siraj M, AU - Wang,Kai, AU - Khaira,Depinder, AU - Palma,Norma A, AU - Chmielecki,Juliann, AU - Palmer,Gary A, AU - Morosini,Deborah, AU - Elvin,Julia A, AU - Fernandez,Sandra V, AU - Miller,Vincent A, AU - Stephens,Philip J, AU - Cristofanilli,Massimo, Y1 - 2015/10/12/ PY - 2015/06/23/received PY - 2015/10/03/accepted PY - 2015/10/14/entrez PY - 2015/10/16/pubmed PY - 2016/8/9/medline KW - Comprehensive genomic profiling KW - EGFR KW - ERBB2 KW - Inflammatory breast cancer KW - MYC KW - NGS SP - 155 EP - 62 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 154 IS - 1 N2 - 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. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/26458824/Comprehensive_genomic_profiling_of_inflammatory_breast_cancer_cases_reveals_a_high_frequency_of_clinically_relevant_genomic_alterations_ L2 - https://doi.org/10.1007/s10549-015-3592-z DB - PRIME DP - Unbound Medicine ER -