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Poster Display session 2

5737 - PAM50 and CGH-array genomic characterization of HER2-Equivocal Breast Cancers defined by the 2018 ASCO/CAP recommendations.

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Breast Cancer

Presenters

Carine Ngo

Citation

Annals of Oncology (2019) 30 (suppl_5): v55-v98. 10.1093/annonc/mdz240

Authors

C. Ngo1, E. Borcoman2, A. Rapinat3, F. Simaga1, N. Mouterfi1, O. Mariani4, L. Fuhrmann1, E. Jeannot1, M. Lae1, J. Pierga5, D. Gentien3, G. Pierron1, P. Morel6, H.A. Brauer6, A. Vincent-Salomon7

Author affiliations

  • 1 Department Of Diagnostic And Theranostic Medicine, Institut Curie, 75005 - Paris/FR
  • 2 Department Of Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 3 Genomic Platform, Institut Curie, 75005 - Paris/FR
  • 4 Department Of Pathology, Institut Curie, 75005 - Paris/FR
  • 5 Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 6 Medical, NanoString Technologies, 75015 - Paris/FR
  • 7 Pathology, Institut Curie, 75005 - Paris/FR
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Resources

Abstract 5737

Background

HER2 breast cancer status determines patients’ eligibility for targeted therapy. HER2 level of amplification is associated with a better response to anti-HER2 therapy. Benefit of anti-HER2 therapy for equivocal cases remains debated.

Methods

We aimed to better characterize HER2-equivocal breast cancers by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) according to 2018 ASCO/CAP guidelines using PAM50 gene expression-based molecular subtyping and to investigate genome-wide copy number alterations of these cases. PAM50 (nCounter assay; Nanostring) was performed on RNA from FFPE samples of 60 HER2-equivocal cases. These cases were subsequently analyzed by Agilent 60-mer oligonucleotide microarrays for array-based comparative genomic hybridization (aCGH).

Results

The 60 HER2-equivocal cases were classified as Luminal B in 31 cases (52%), HER2-Enriched in 14 cases (23%), Luminal A in 13 cases (22%) and Basal-like in 2 cases (3%) using PAM50. By IHC, 52 cases (87%) were ER+, 43 (72%) were also PgR+, 40 (67%) were grade III and 45 (75%) showed a high Ki67 > 20%. With aCGH, 23 cases (38%) presented chr 17q large copy number gain, 14 (23%) showed segmental copy number gain including HER2, 10 (17%) showed HER2 amplification, one (2%) showed a large copy number loss and 12 cases (20%) didn’t show any copy number alteration of the chr 17. Out of the 14 PAM50 HER2-Enriched cases, only 5 showed HER2 genomic amplification (Table). In total, 14 cases (23%) were discordant between molecular classification and genomic alteration status of the chr 17.Table:

260P

Genomic alterations of chromosome 17Basal- likeHER2- EnrichedLuminal ALuminal BTotal
HER2 amplified052310
Large copy number gain0151723
Segmental copy number gain254314
No alteration032712
Large copy number loss00011
Total214133160

Conclusions

Using PAM50, the majority of HER2-equivocal cases were classified as Luminal tumors (Luminal B 52% and A 22%) and harbored mostly at the genomic level chr 17 segmental or large copy number gains. As there is no evidence of benefit of anti-HER2 therapy in these cases, it emphasizes the need of genomic status determination of HER2-equivocal cases.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Anne Vincent-Salomon.

Funding

Has not received any funding.

Disclosure

P. Morel: Full / Part-time employment: Nanostring. H.A. Brauer: Full / Part-time employment: Nanosting. A. Vincent-Salomon: Advisory / Consultancy, Consulting fees: Roche; Advisory / Consultancy, Consulting fees: AstraZeneca; Non-remunerated activity/ies, Contracted Research: Nanostring. All other authors have declared no conflicts of interest.

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