Quantitative justification of the change from 10% to 30% for human epidermal growth factor receptor 2 scoring in the American Society of Clinical Oncology/College of American Pathologists guidelines: tumor heterogeneity in breast cancer and its implications for tissue microarray based assessment of outcome
- PMID: 18048824
- DOI: 10.1200/JCO.2007.12.8033
Quantitative justification of the change from 10% to 30% for human epidermal growth factor receptor 2 scoring in the American Society of Clinical Oncology/College of American Pathologists guidelines: tumor heterogeneity in breast cancer and its implications for tissue microarray based assessment of outcome
Abstract
Purpose: The variability in scoring of immunohistochemistry, whether a result of true heterogeneity or artifacts in preparation, has led to decreased reliability in companion diagnostics and the recommendation for new standards (eg, the American Society of Clinical Oncology/College of American Pathologists [ASCO-CAP] guidelines). The basis of this problem is the amount of tissue required to be representative of an entire tumor. Because protein expression on tissue microarrays (TMAs) can be rigorously measured and one 0.6-mm spot is equivalent to two to three high-power fields, we used TMAs to assess levels of heterogeneity and to determine optimal representation as a function of outcome.
Patients and methods: We analyzed estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) expression in two cohorts (n = 676 and n = 152) on a series of four to five separate TMA cores and assessed heterogeneity by linear regression analysis. Minimum, average, and maximum scores were generated for each set, which were then assessed for prognostic and predictive value.
Results: Each marker shows some heterogeneity, but average r values between 0.7 and 0.8 are seen between TMA spots. Analysis for prognostic value shows that the highest maximum score (of five spots) is the most prognostic for ER, whereas a high HER-2 minimum score is most prognostic for poor outcome and most predictive of response to trastuzumab.
Conclusion: These results suggest that the representivity required for each biomarker may be a function of its role in tumorigenesis. Furthermore, these results provide scientific basis for the ASCO-CAP guidelines for assessment of HER-2 expression but perhaps suggest that the 30% figure is still too conservative.
Similar articles
-
Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group.J Clin Oncol. 2008 Mar 20;26(9):1419-26. doi: 10.1200/JCO.2007.14.5565. Epub 2008 Feb 19. J Clin Oncol. 2008. PMID: 18285604 Clinical Trial.
-
Surgical specimen can be replaced by core samples in assessment of ER, PR and HER-2 for invasive breast cancer.Acta Oncol. 2008;47(1):38-46. doi: 10.1080/02841860701441822. Acta Oncol. 2008. PMID: 17851859
-
Semi-quantitative scoring of potentially predictive markers for endocrine treatment of breast cancer: a comparison between whole sections and tissue microarrays.J Clin Pathol. 2007 Apr;60(4):397-404. doi: 10.1136/jcp.2005.034447. Epub 2006 Jun 14. J Clin Pathol. 2007. PMID: 16775123 Free PMC article.
-
Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations.J Clin Oncol. 2009 Mar 10;27(8):1323-33. doi: 10.1200/JCO.2007.14.8197. Epub 2009 Feb 9. J Clin Oncol. 2009. PMID: 19204209 Review.
-
Multigene classifiers, prognostic factors, and predictors of breast cancer clinical outcome.Adv Anat Pathol. 2009 Jul;16(4):204-15. doi: 10.1097/PAP.0b013e3181a9d4bf. Adv Anat Pathol. 2009. PMID: 19546609 Review.
Cited by
-
Characterization of breast cancer subtypes based on quantitative assessment of intratumoral heterogeneity using dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging.Eur Radiol. 2022 Feb;32(2):822-833. doi: 10.1007/s00330-021-08166-4. Epub 2021 Aug 4. Eur Radiol. 2022. PMID: 34345946
-
Agreement between dynamic contrast-enhanced magnetic resonance imaging and pathologic tumour size of breast cancer and analysis of the correlation with BI-RADS descriptors.Pol J Radiol. 2019 Dec 27;84:e616-e624. doi: 10.5114/pjr.2019.92285. eCollection 2019. Pol J Radiol. 2019. PMID: 32082460 Free PMC article.
-
HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation.J Pathol Transl Med. 2020 Jan;54(1):34-44. doi: 10.4132/jptm.2019.11.03. Epub 2019 Nov 6. J Pathol Transl Med. 2020. PMID: 31693827 Free PMC article. Review.
-
Kinetic Features of Invasive Breast Cancers on Computer-Aided Diagnosis Using 3T MRI Data: Correlation with Clinical and Pathologic Prognostic Factors.Korean J Radiol. 2019 Mar;20(3):411-421. doi: 10.3348/kjr.2018.0587. Korean J Radiol. 2019. PMID: 30799572 Free PMC article.
-
Risk stratification of ductal carcinoma in situ using whole-lesion histogram analysis of the apparent diffusion coefficient.Eur Radiol. 2019 Feb;29(2):485-493. doi: 10.1007/s00330-018-5666-x. Epub 2018 Aug 2. Eur Radiol. 2019. PMID: 30073498
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous