Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy
| Autor: | Judith Lindner, J Huober, Knut Engels, Carsten Denkert, Christian Schem, Beyhan Ataseven, Cornelia Liedtke, Thomas Karn, G. von Minckwitz, Silvia Darb-Esfahani, Hans Tesch, Brigitte Rack, Michael Untch, Stephan Gade, V Müller, Bruno Valentin Sinn, S. Loibl, Peter A. Fasching, Berit M. Pfitzner, Bernd Gerber, F. Pommerenke |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
medicine.medical_specialty Receptor ErbB-2 medicine.medical_treatment Population Triple Negative Breast Neoplasms Disease-Free Survival Breast cancer Medizinische Fakultät Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Biomarkers Tumor Humans Osteonectin Prospective Studies ddc:610 education Cyclophosphamide Chemotherapy education.field_of_study Predictive marker business.industry Albumin Hematology Middle Aged medicine.disease Primary tumor Neoadjuvant Therapy 3. Good health Treatment Outcome Receptors Estrogen Doxorubicin Biomarker (medicine) Immunohistochemistry Female Taxoids business Receptors Progesterone |
| Zdroj: | Annals of Oncology |
| Popis: | Background: Secreted protein acidic and rich in cysteine (SPARC) has been suggested as a new biomarker and therapeutic target in breast cancer, as well as other tumor types. Patients and methods: We evaluated the frequency of SPARC expression among different molecular breast cancer subtypes and its role for therapy response after neoadjuvant chemotherapy. In this study, pretherapeutic core biopsies of 667 patients from the neoadjuvant GeparTrio trial were evaluated for SPARC expression by immunohistochemistry using a standardized immunoreactive score (IRS). Results: An increased SPARC expression (IRS ≥6) was observed in 26% of all tumors. In triple-negative tumors, SPARC expression was increased in 37% of tumors, compared with other molecular subtypes (23% HR+/HER2−, 29% HR+/HER2+ and 22% HR−/HER2+; P = 0.038). Increased SPARC expression was associated with an increased pathological complete response (pCR) rate of 27%, compared with 15% in tumors with low SPARC expression (P < 0.001). In the triple-negative subgroup, pCR rates were 47% in tumors with high SPARC expression, compared with 26% in tumors with low SPARC expression (P = 0.032). In multivariable analysis, SPARC was independently predictive in the overall population (P = 0.010) as well as the triple-negative subgroup (P = 0.036). Conclusions: SPARC is frequently expressed in breast cancer with triple-negative breast cancer revealing the highest expression rate. High SPARC expression of the primary tumor is associated with a higher chance of achieving a pathological complete remission after TAC or TAC-NX chemotherapy. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of albumin bound drugs, SPARC should be further evaluated as a predictive marker especially for response to albumin-bound drugs like nab-paclitaxel. Clinical trial number: NCT00544765. |
| Databáze: | OpenAIRE |
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