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.
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).
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. 260PGenomic alterations of chromosome 17 Basal- like HER2- Enriched Luminal A Luminal B Total HER2 amplified 0 5 2 3 10 Large copy number gain 0 1 5 17 23 Segmental copy number gain 2 5 4 3 14 No alteration 0 3 2 7 12 Large copy number loss 0 0 0 1 1 Total 2 14 13 31 60
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.
Anne Vincent-Salomon.
Has not received any funding.
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.