Abstract P3-08-16: ER, PR and HER2 biomarkers in UK and Irish clinical breast cancer testing: analysis of results from &gt;168,000 patients
Authors: Dodson A , Parry S , Ibrahim M , Bartlett J , Dowsett M , Miller K 
Published: February 2018

Abstract
AIMS
To describe and analyse &gt;168,000 sets of results from clinical breast biomarker testing carried-out between 2009 and 2016 in the UK and Republic of Ireland, focussing on biological relationships. To present robust confirmatory evidence on known associations and provide new data on previously undescribed or unconfirmed ones.
BACKGROUND
Between Jan-2009 and Jan-2016 the UK National External Quality Assessment Scheme for Immunocytochemistry and In-situ Hybridisation (UK NEQAS ICC&ISH) collected results on clinical breast cancer testing, comprehensively for human epidermal growth factor receptor-2 (HER2) and optionally for estrogen receptor (ER) and progesterone receptor (PR), from most UK and Irish testing centres. Primary objectives were to assess and, where indicated achieve improvements in testing quality. The size and scope of the data-set is unparalleled in the literature and represent a significant reference resource for the breast cancer community.
METHODS
UK NEQAS ICC&ISH created and curated an on-line data-entry system allowing centres to systematically collect their own HER2, ER and PR results from clinical testing; for HER2, immunohistochemical (IHC) and in-situ hybridisation (ISH) data were collected; for ER and PR, IHC results could be entered according to local practise format. Tools and guidance were provided enabling centres to analyse their data for local audit and quality assurance. Clinicopathologic data was also collected, including: patient age at diagnosis, histological tumor type, tumor grade, site/stage (primary, recurrence, metastasis) and sample type (core, excision).
RESULTS
Data are present on 168,793 patients. 173 centres contributed ≥100 entries (96% of total). Median age was 62 years (IQR: 51-72). Tumor type was stated in 42%: 76% were invasive ductal, and 13% invasive lobular carcinoma. Grade was stated in 56%: 15% were Grade 1, 55% Grade 2 and 30% Grade 3. Site/stage was stated in 56%: 92% were primary, 2% recurrent and 6% metastatic. Sample type was stated in 70%: 75% were cores and 25%, excision.
Receptor statuses were available as follows; HER2 (100%): 87% negative, 13% positive; ER (45%): 15% negative, 85% positive; PR (31%): 29% negative, 71% positive.
HER2 data were available as follows; category by IHC: 91%; amplification status by ISH: 15%; HER2 gene/chromosome 17 (CEP17) ratio: 15% (86% of which were IHC 2+); HER2 gene copy number: 7%; CEP17 copy number: 7%.
HER2-positive rate was 24% in ER-negative and 11% in ER-positive cases. HER2-positive status was negatively associated with increasing ER positivity (rho -0.22, P&lt;0.001). 71% of HER2-positive cases were ER-positive and 29% were ER-negative. The HER2 2+ rate was 14% in ER-negative and 21% in ER-positive cases. Considering only IHC 2+ cases, median HER2 copy number was 5.4 in ER-negative and 4.4 in ER-positive disease.
Comprehensive description of significant associations for all parameters will be presented.
CONCLUSION
The unique size and scope of this data-set has allowed confirmation of known associations for HER2, ER and PR with clinicopathologic and biological characteristics in breast cancer to very high confidence levels, and has uncovered previously undescribed relationships in both ER-positive and ER-negative disease.
Citation Format: Dodson A, Parry S, Ibrahim M, Bartlett J, Dowsett M, Miller K. ER, PR and HER2 biomarkers in UK and Irish clinical breast cancer testing: analysis of results from &gt;168,000 patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-16.