C. García (Madrid, Spain)
University Hospital 12 De OctubreAuthor Of 1 Presentation
- R. Sanchez Bayona (Madrid, Spain)
- A. Luna (Madrid, Spain)
- P. Tolosa (Madrid, Spain)
- A. Sánchez De Torre (Madrid, Spain)
- A. Castelo (Madrid, Spain)
- M. Marín (Madrid, Spain)
- C. García (Madrid, Spain)
- V. Boni (Madrid, Spain)
- E. Bernal Hertfelder (Madrid, Spain)
- E. Vega (Madrid, Spain)
- B. Rojas (Madrid, Spain)
- R. Bratos (Madrid, Spain)
- M. Martínez (Madrid, Spain)
- Á. Díaz Bermejo (Madrid, Spain)
- L. Lema (Madrid, Spain)
- L. Manso (Madrid, Spain)
- E. Ciruelos (Madrid, Spain)
22P - HER2-low vs HER2-zero metastatic breast carcinoma: a clinical and genomic descriptive analysis.
Abstract
Background
HER2-low breast cancer (BC) is defined by an immunohistochemistry (IHC) assay score 1+ or 2+ with negative in situ hybridization (ISH). Genomic characterization of this subset of BC is still limited. We aimed to compare the genomic alterations found in a subgroup of HER2-low metastatic BC versus HER2-zero tumors (IHC score 0) in order to identify potential biomarkers.
Methods
A retrospective analysis was carried out in a sample of 121 metastatic BC patients from Hospital Universitario 12 de Octubre and HM CIOCC (Madrid, Spain) collected from 2017-2020. Next-generation sequencing (NGS) was performed in formalin-fixed paraffin embedded (FFPE) samples of BC. Biopsies included both primary or metastatic tumor, whichever most recent/accesible was available. Somatic mutations and copy number variations (gains and loss) were gathered from the NGS reports. Two-sided Chi-Square test was used for comparisons of proportions between groups and p values below 0.05 were deemed statistically significant.
Results
We identified a total of 67 HER2-low and 54 HER2-zero breast carcinomas. Both groups were similar in the median age of patients, menopausal status and metastatic pattern. The most frequent phenotype was luminal B for both groups, with a significantly higher prevalence in HER2-low carcinomas (65.7% and 37.0%, p<0.01). The most frequently mutated genes were (Table) PIK3CA (31.3% vs 35.2%, p=0.34) and TP53 (34.3% vs 48.2%, p=0.12) in both HER2-low and HER2-zero categories, respectively. We observed a higher prevalence of FGFR1 amplification (defined as ≥10 copy number gain) in the HER2-low group (12% vs 1.8%, p=0.03) compared to HER2-zero carcinomas. Only gene alterations with a frequency of ≥5% in any group are shown
HER2-LOW HER2-ZERO p value 67 54 49 (29-83) 46 (27-79) 0.11 31 (48.4) 29 (48.3) 0.99 0.43 47.7 45.9 12.3 19.7 12.3 16.4 27.7 18.0 <0.01 12 (17.9) 15 (27.8) 44 (65.7) 20 (37.0) 11 (16.4) 18 (33.2) 21 (31.3) 19 (35.2) 0.34 23 (34.3) 26 (48.2) 0.12 7 (10.8) 7 (13.0) 0.66 9 (13.4) 3 (5.5) 0.22 4 (6.0) 3 (5.5) 0.92 6 (9.0) 4 (7.4) 0.76 4 (6.0) 2 (3.7) 0.57 7 (10.4) 6 (11.0) 0.91 8 (12.0) 1 (1.8) 0.03
Conclusions
In our sample, PIK3CA and TP53 were the most frequently mutated genes in both HER2-low and HER2-zero breast carcinomas. FGFR1 amplification was more prevalent in the HER2-low category compared to HER2-zero tumors. This finding needs to be further confirmed as a potential target in this subset of patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Sanchez Bayona: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. P. Tolosa: Speaker Bureau/Expert testimony: AstraZeneca, Amgen, MSD, Roche and Pfizer. E.M. Ciruelos: Advisory/Consultancy: Pfizer, Eli Lilly, Roche, Novartis, AstraZeneca and MSD; Speaker Bureau/Expert testimony: Roche, Pfizer and Eli Lilly; Travel/Accommodation/Expenses: Roche, Pfizer. All other authors have declared no conflicts of interest.