Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study

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dc.contributor.authorBilous, M.
dc.contributor.authorAdes, C.
dc.contributor.authorAmes, J.
dc.contributor.authorBishop, J.
dc.contributor.authorBrown, R.
dc.contributor.authorCooke, B.
dc.contributor.authorCummings, M.
dc.contributor.authorFarshid, G.
dc.contributor.authorField, A.
dc.contributor.authorMorey, A.
dc.contributor.authorMcKenzie, P.
dc.contributor.authorRaymond, W.
dc.contributor.authorRobbins, P.
dc.contributor.authorTan, L.
dc.date.issued2003
dc.description.abstractThe tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.
dc.description.statementofresponsibilityM Bilous, C Ades, J Armes, J Bishop, R Brown, B Cooke, M Cummings, G Farshid, A Field, A Morey, P McKenzie, W Raymond, P Robbins, L Tan
dc.identifier.citationThe Breast, 2003; 12(2):92-98
dc.identifier.doi10.1016/S0960-9776(02)00273-4
dc.identifier.issn0960-9776
dc.identifier.issn1532-3080
dc.identifier.orcidFarshid, G. [0000-0002-2056-0561]
dc.identifier.urihttp://hdl.handle.net/2440/5571
dc.language.isoen
dc.publisherChurchill Livingstone
dc.rightsCopyright © 2003 Elsevier Science Ltd. All rights reserved.
dc.source.urihttps://doi.org/10.1016/s0960-9776(02)00273-4
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectReceptor, erbB-2
dc.subjectObserver Variation
dc.subjectBiopsy, Needle
dc.subjectPrognosis
dc.subjectImmunohistochemistry
dc.subjectIn Situ Hybridization
dc.subjectProbability
dc.subjectRisk Assessment
dc.subjectSensitivity and Specificity
dc.subjectProspective Studies
dc.subjectPredictive Value of Tests
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectInternational Cooperation
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectBiomarkers, Tumor
dc.titlePredicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study
dc.typeJournal article
pubs.publication-statusPublished

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