Identification of biology-based breast cancer types with distinct predictive and prognostic features : role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy

  • Introduction: Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for operable breast cancer to test for associations with pathological complete response (pCR) and disease-free survival (DFS). Particularly, we evaluated if interactions between hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression might lead to a different clinical behavior of HR+/HER2+ coexpressing and HR+/HER2- tumors and whether subgroups of triple negative tumors might be identified by the help of Ki67 labeling index, cytokeratin 5/6 (CK5/6), as well as cyclooxygenase-2 (COX-2), and Y-box binding protein 1 (YB-1) expression. Methods: Expression analysis was performed using immunohistochemistry and silver-enhanced in situ hybridization on tissue microarrays (TMAs) of pretherapeutic core biopsies. Results: pCR rates were significantly different between the biology-based tumor types (P = 0.044) with HR+/HER2+ and HR-/HER2- tumors having higher pCR rates than HR+/HER2-tumors. Ki67 labeling index, confirmed as significant predictor of pCR in the whole cohort (P = 0.001), identified HR-/HER- (triple negative) carcinomas with a higher chance for a pCR (P = 0.006). Biology-based tumor type (P = 0.046 for HR+/HER2+vs. HR+/HER2-), Ki67 labeling index (P = 0.028), and treatment arm (P = 0.036) were independent predictors of pCR in a multivariate model. DFS was different in the biology-based tumor types (P < 0.0001) with HR+/HER2- and HR+/HER2+ tumors having the best prognosis and HR-/HER2+ tumors showing the worst outcome. Biology-based tumor type was an independent prognostic factor for DFS in multivariate analysis (P < 0.001). Conclusions: Our data demonstrate that a biology-based breast cancer classification using estrogen receptor (ER), progesterone receptor (PgR), and HER2 bears independent predictive and prognostic potential. The HR+/HER2+ coexpressing carcinomas emerged as a group of tumors with a good response rate to neoadjuvant chemotherapy and a favorable prognosis. HR+/HER2- tumors had a good prognosis irrespective of a pCR, whereas patients with HR-/HER- and HR-/HER+ tumors, especially if they had not achieved a pCR, had an unfavorable prognosis and are in need of additional treatment options. Trial registration ClinicalTrials.gov identifier: NCT00793377

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Author:Silvia Darb-Esfahani, Sibylle Loibl, Berit Maria Müller, Marc Roller, Carsten Michael Denkert, Martina Komor, Karsten Schlüns, Jens-Uwe Blohmer, Jan Budczies, Bernd Gerber, Aurelia Noske, Andreas Du Bois, Wilko Weichert, Christian Jackisch, Manfred Dietel, Klaus Richter, Manfred Kaufmann, Gunter von Minckwitz
URN:urn:nbn:de:hebis:30-71504
DOI:https://doi.org/10.1186/bcr2363
ISSN:1465-542X
ISSN:1465-5411
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/19758440
Parent Title (English):Breast cancer research
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2009/10/06
Date of first Publication:2009/09/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/10/06
Volume:11
Issue:5, Art. R69
Page Number:11
First Page:1
Last Page:11
Note:
© 2009 Darb-Esfahani et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative commons Attributions License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source:Breast Cancer Research 2009, 11:R69, No. 5, (doi:10.1186/bcr2363) ; http://breast-cancer-research.com/content/11/5/R69
HeBIS-PPN:219481997
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 2.0