The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

The 70-gene signature (MammaPrint™) is a prognostic tool used to guide adjuvant treatment decisions. The aim of this study was to assess its value to predict chemosensitivity in the neoadjuvant setting. We obtained the 70-gene profile of stage II–III patients prior to neoadjuvant chemotherapy and classified the prognosis-signatures. Pathological complete remission (pCR) was used to measure chemosensitivity. Among 167 patients, 144 (86%) were having a poor and 23 (14%) a good prognosis-signature. None of the good prognosis-signature patients achieved a pCR (0/23), whereas 29/144 patients (20%) in the poor prognosis-signature group did (P = 0.015). All triple-negative tumors (n = 38) had a poor prognosis-signature. Within the non triple-negative subgroup, the response of the primary tumor remained associated with the classification of the prognosis-signature (P = 0.023). A pCR is unlikely to be achieved in tumors that have a good prognosis-signature. Tumors with a poor prognosis-signature are more sensitive to chemotherapy.

[1]  E. Perez,et al.  Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. , 2005, Clinical breast cancer.

[2]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. , 1999, Critical reviews in oncology/hematology.

[3]  Suzanne F. Jones,et al.  Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  M. Cronin,et al.  Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Wim H van Harten,et al.  Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). , 2007, The Lancet. Oncology.

[6]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[7]  Roman Rouzier,et al.  Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  L. V. van't Veer,et al.  Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. , 2006, Journal of the National Cancer Institute.

[9]  A. Hart,et al.  Validation of 70-gene prognosis signature in node-negative breast cancer , 2009, Breast Cancer Research and Treatment.

[10]  M. J. van de Vijver,et al.  Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.

[12]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[13]  J. O’Shaughnessy,et al.  Capecitabine/Taxane combination therapy: evolving clinical utility in breast cancer. , 2006, Clinical breast cancer.

[14]  C. V. D. van de Velde,et al.  Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  N. Dandachi,et al.  Comparison of chromogenic in situ hybridization with other methodologies for HER2 status assesment in breast cancer , 2004, Journal of Molecular Histology.

[16]  M. Merino,et al.  A Phase II Trial of Neoadjuvant Docetaxel and Capecitabine for Locally Advanced Breast Cancer , 2004, Clinical Cancer Research.

[17]  C. Perou,et al.  The Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes , 2007, Clinical Cancer Research.

[18]  A. Witteveen,et al.  Converting a breast cancer microarray signature into a high-throughput diagnostic test , 2006, BMC Genomics.

[19]  Catherine Legrand 1687Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials : Early Breast Cancer Trialists' Collaborative Group (EBCTCG) , 2005 .

[20]  P. Ravdin,et al.  Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  A. Glas,et al.  The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study , 2009, Breast Cancer Research and Treatment.

[22]  Kenneth G A Gilhuijs,et al.  Dynamic contrast-enhanced MRI for prediction of breast cancer response to neoadjuvant chemotherapy: initial results. , 2008, AJR. American journal of roentgenology.

[23]  Y Wang,et al.  Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials , 2005, The Lancet.

[24]  G. Hortobagyi,et al.  Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  青儀 健二郎,et al.  What's going on 乳癌 Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group(EBCTCG). Lancet. 2005; 365: 1687-717. PMID: 15894097.--早期乳癌に対する化学療法・内分泌療法が乳癌再発・15年生存率に及 , 2006 .

[26]  S. Paik,et al.  Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  Annuska M Glas,et al.  Gene expression profiles of primary breast tumors maintained in distant metastases , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  L. V. van't Veer,et al.  Clinical application of the 70-gene profile: the MINDACT trial. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  A. Gown,et al.  Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma , 2004, Clinical Cancer Research.

[30]  Barbara L. Smith,et al.  Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Van,et al.  A gene-expression signature as a predictor of survival in breast cancer. , 2002, The New England journal of medicine.