Abstract P1-18-06: Targetable ERBB2 mutations independently predict an aggressive phenotype in primary, ERBB2 non-amplified, hormone receptor positive lobular breast cancer
| Autor: | Andrew R. Green, Ken Shirabe, Wilbert Zwart, Simon J Johnston, Steffi Oesterreich, David M. Heery, Sasagu Kurozumi, Emad A. Rakha, Ian O. Ellis, Takaaki Fujii |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
business.industry Cancer Ductal carcinoma medicine.disease medicine.anatomical_structure Germline mutation Breast cancer Oncology Hormone receptor Invasive lobular carcinoma Neratinib medicine Cancer research skin and connective tissue diseases business neoplasms Lymph node medicine.drug |
| Zdroj: | Cancer Research. 80:P1-18 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Invasive lobular carcinoma accounts for 10-15% of breast cancer cases and typically expresses hormone receptors. Despite this, lobular tumours respond less well to endocrine therapy, and long-term patient outcomes are inferior to those with other breast cancer subtypes. In primary lobular tumours, HER2 is rarely overexpressed due to relative infrequency of ERBB2 amplification. However, somatic mutation of ERBB2 may provide an alternative and tractable mechanism for upregulation of HER2 activity, which can be effectively targeted using a second generation HER2/EGFR tyrosine kinase inhibitor such as neratinib. In this study we performed comparative in silico analysis of ER/PR(+), HER2(-) cases of invasive lobular (N=352) and ductal carcinoma (N=1,820) from the three largest primary breast cancer clinical datasets with somatic mutations called from next generation sequencing (TCGA, METABRIC and MSK, N=2,172). Using existing functional data from in vitro, cell line and xenograft experiments, ERBB2 mutations were stratified into known ‘oncogenic‘ or ‘uncharacterized‘ and integrated with lymph node status, tumour size and grade. The primary endpoint was overall survival as these data were available across datasets. We find that lobular tumours comprise 11% of all cases but contain 40% of the somatic mutations in ERBB2 in the dataset. The overall rate of mutated ERBB2 in lobular cases is 6% (N=21) versus 1.8% (N=32) in ductal cases (p Citation Format: Sasagu Kurozumi, Andrew R Green, Ian O Ellis, Emad A Rakha, Takaaki Fujii, Ken Shirabe, David Heery, Wilbert Zwart, Steffi Oesterreich, Simon J Johnston. Targetable ERBB2 mutations independently predict an aggressive phenotype in primary, ERBB2 non-amplified, hormone receptor positive lobular breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-06. |
| Databáze: | OpenAIRE |
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