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
| Autor: | Jens-Uwe Blohmer, Aurelia Noske, Jan Budczies, Silvia Darb-Esfahani, Manfred Kaufmann, Karsten Schlüns, Bernd Gerber, Martina Komor, Wilko Weichert, Marc Roller, Gunter von Minckwitz, Christian Jackisch, Berit Maria Müller, Andreas du Bois, Manfred Dietel, Klaus Richter, Carsten Denkert, Sibylle Loibl |
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| Rok vydání: | 2009 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Receptor ErbB-2 medicine.medical_treatment Biopsy Estrogen receptor Breast Neoplasms Docetaxel Biology Disease-Free Survival Cohort Studies Breast cancer Surgical oncology Internal medicine Progesterone receptor Antineoplastic Combined Chemotherapy Protocols Research article medicine Humans ddc:610 skin and connective tissue diseases Cyclophosphamide Neoadjuvant therapy In Situ Hybridization Aged Medicine(all) Tissue microarray Nuclear Proteins Middle Aged medicine.disease Immunohistochemistry Neoadjuvant Therapy Carcinoma Ductal DNA-Binding Proteins Receptors Estrogen Cyclooxygenase 2 Doxorubicin Female Taxoids Y-Box-Binding Protein 1 Breast cancer classification Receptors Progesterone medicine.drug |
| Zdroj: | Breast Cancer Research : BCR |
| ISSN: | 1465-542X |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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