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Gene expression and pathologic response to neoadjuvant chemotherapy in breast cancer

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Abstract

Pathologic complete response after neoadjuvant systemic treatment appears to be a valid surrogate for better overall survival in breast cancer patients. Currently, together with standard clinicopathologic assessment, novel molecular biomarkers are being exhaustively tested in order to look into the heterogeneity of breast cancer. The aim of our study was to examine an association between 23-gene real-time-PCR expression assay including ABCB1, ABCC1, BAX, BBC3, BCL2, CASP3, CYP2D6, ERCC1, FOXC1, GAPDH, IGF1R, IRF1, MAP2, MAPK 8, MAPK9, MKI67, MMP9, NCOA3, PARP1, PIK3CA, TGFB3, TOP2A, and YWHAZ receptor status of breast cancer core biopsies sampled before neoadjuvant chemotherapy (anthracycline and taxanes) and pathologic response. Core-needle biopsies were collected from 42 female patients with inoperable locally advanced breast cancer or resectable tumors suitable for downstaging, before any treatment. Expressions of 23 genes were determined by means of TagMan low density arrays. Analysis of variance was used to select genes with discriminatory potential between receptor subtypes. We introduced a correction for false discovery rates (presented as q values) due to multiple hypothesis testing. Statistical analysis showed that seven genes out of a 23-gene real-time-PCR expression assay differed significantly in relation to pathologic response regardless of breast cancer subtypes. Among these genes, we identified: BAX (p = 0.0146), CYP2D6 (p = 0.0063), ERCC1 (p = 0.0231), FOXC1 (p = 0.0048), IRF1 (p = 0.0022), MAP2 (p = 0.0011), and MKI67 (p = 0.0332). The assessment of core biopsy gene profiles and receptor-based subtypes, before neoadjuvant therapy seems to predict response or resistance and to define new signaling pathways to provide more powerful classifiers in breast cancer, hence the need for further research.

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Acknowledgment

This work was supported by the grant of the Ministry of Science, Poland, NN402350838.

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Authors and Affiliations

  1. Department of Surgical Oncology, Cancer Center, Copernicus Memorial Hospital, Paderewskiego 4, 93-509, Lodz, Poland

    Agnieszka Kolacinska & Zbigniew Morawiec

  2. Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland

    Wojciech Fendler

  3. Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland

    Janusz Szemraj

  4. Central Laboratory, Medical University of Lodz, Lodz, Poland

    Bozena Szymanska & Zofia Pawlowska

  5. Department of Radiology, Cancer Center, Copernicus Memorial Hospital, Lodz, Poland

    Ewa Borowska-Garganisz & Magdalena Nowik

  6. Department of Radiotherapy, Cancer Center, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland

    Justyna Chalubinska

  7. Department of Pathology, Medical University of Lodz, Lodz, Poland

    Robert Kubiak

  8. Department of Proliferative Diseases, Cancer Center, Copernicus Memorial Hospital, Lodz, Poland

    Maria Blasinska-Morawiec

  9. Department of Chemotherapy, Medical University of Lodz, Lodz, Poland

    Piotr Potemski

  10. Department of Surgical Oncology, Medical University of Lodz, Lodz, Poland

    Arkadiusz Jeziorski

Authors
  1. Agnieszka Kolacinska
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  2. Wojciech Fendler
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  3. Janusz Szemraj
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  4. Bozena Szymanska
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  5. Ewa Borowska-Garganisz
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  6. Magdalena Nowik
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  7. Justyna Chalubinska
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  8. Robert Kubiak
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  9. Zofia Pawlowska
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  10. Maria Blasinska-Morawiec
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  11. Piotr Potemski
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  12. Arkadiusz Jeziorski
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  13. Zbigniew Morawiec
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Correspondence to Agnieszka Kolacinska.

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Kolacinska, A., Fendler, W., Szemraj, J. et al. Gene expression and pathologic response to neoadjuvant chemotherapy in breast cancer. Mol Biol Rep 39, 7435–7441 (2012). https://doi.org/10.1007/s11033-012-1576-1

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  • DOI: https://doi.org/10.1007/s11033-012-1576-1

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