Prognostic and predictive factors.

Prognostic factors are key elements for medical oncologists to select, among the group of patients with early breast cancer, those who are candidates for an adjuvant treatment based on their risk of tumor relapse. Predictive factors drive the decision of which type(s) of treatment should be given. If we perform a literature search on prognostic and predictive factors in breast cancer we immediately realize how redundant is the number of markers that have been/are being evaluated and a dedicated book would be needed to review all of them critically. So, for the purpose of writing this chapter, I have decided to start from markers whose roles have been established to be relevant for patient care by an international panel of breast cancer experts [1].

[1]  Greg Yothers,et al.  Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. , 2005, The New England journal of medicine.

[2]  D A Berry,et al.  erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. , 1998, Journal of the National Cancer Institute.

[3]  A. Sapino,et al.  Meta‐analysis of non‐sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer , 2004, The British journal of surgery.

[4]  M. West,et al.  Gene expression predictors of breast cancer outcomes , 2003, The Lancet.

[5]  Roman Rouzier,et al.  Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Berry,et al.  HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  S. Ménard,et al.  HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  D B Evans,et al.  Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  A. Bianco,et al.  c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  A. Luini,et al.  Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  M. Gnant,et al.  TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  Jorma Isola,et al.  Characterization of topoisomerase IIα gene amplification and deletion in breast cancer , 1999 .

[13]  J. Coindre,et al.  Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers. , 1998, European journal of cancer.

[14]  W. McCaskill-Stevens,et al.  The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  D. Larsimont,et al.  HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  Carlos Caldas,et al.  Identification and validation of prognostic markers in breast cancer with the complementary use of array‐CGH and tissue microarrays , 2005, The Journal of pathology.

[17]  M. Untch,et al.  Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. , 2004, Journal of the National Cancer Institute.

[18]  C. Osborne,et al.  HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  C. Sotiriou,et al.  Correlation between topoisomerase-IIalpha gene amplification and protein expression in HER-2 amplified breast cancer. , 2004, International journal of oncology.

[20]  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.

[21]  M. R. Shetty,et al.  Tumor size and axillary metastasis, a correlative occurrence in 1244 cases of breast cancer between 1980 and 1995. , 1997, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[22]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  C. Osborne,et al.  bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  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.

[25]  W. Yang,et al.  Impact of patient age on the outcome of primary breast carcinoma * , 2002, Journal of surgical oncology.

[26]  S. Martino,et al.  HER2 predicts benefit from adjuvant paclitaxel after AC in node-positive breast cancer: CALGB 9344. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  A. Goldhirsch,et al.  Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. , 1985, Human pathology.

[28]  S. Pinder,et al.  Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long‐term follow‐up , 1994, Histopathology.

[29]  A. Luini,et al.  Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[30]  M. Gnant,et al.  TP 53 Mutation and p 53 Overexpression for Prediction of Response to Neoadjuvant Treatment in Breast Cancer Patients 1 , 2000 .

[31]  D. Larsimont,et al.  HER-2 and topo-isomerase IIalpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  K. Bloom,et al.  The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. , 2003, The oncologist.

[33]  S. Paik,et al.  HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15. , 2000, Journal of the National Cancer Institute.

[34]  M. Fernö,et al.  ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[35]  J. Foekens,et al.  Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer. , 2004, Clinical breast cancer.

[36]  D. Maloney,et al.  Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  R. Gelber,et al.  Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[38]  Z. Hall Cancer , 1906, The Hospital.

[39]  A. Harris,et al.  Topoisomerase II alpha co-amplification with erbB2 in human primary breast cancer and breast cancer cell lines: relationship to m-AMSA and mitoxantrone sensitivity. , 1993, Oncogene.

[40]  N. Harbeck P40 Pooled analysis (n=8,377) validates predictive impactof uPA and PAI-1 for response to adjuvant chemotherapy in breast cancer , 2005 .

[41]  S. Martino,et al.  HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

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

[43]  S. Singletary,et al.  Prognostic Factors in Node-Negative Breast Cancer: A Review of Studies With Sample Size More Than 200 and Follow-Up More Than 5 Years , 2002, Annals of surgery.

[44]  Syed Mohsin,et al.  Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer , 2003, The Lancet.

[45]  Irene L Andrulis,et al.  HER2 and responsiveness of breast cancer to adjuvant chemotherapy. , 2006, The New England journal of medicine.

[46]  T. Nishikawa,et al.  The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer , 2003, British Journal of Cancer.

[47]  Jorma Isola,et al.  Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. , 2006, The New England journal of medicine.

[48]  Å. Borg,et al.  Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. , 2000, The American journal of pathology.

[49]  R. Nahta,et al.  HER2 therapy: Molecular mechanisms of trastuzumab resistance , 2006, Breast Cancer Research.

[50]  Philip M. Long,et al.  Breast cancer classification and prognosis based on gene expression profiles from a population-based study , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[51]  C. Redmond,et al.  Pathologic findings from the national surgical adjuvant breast project (protocol 4): Discriminants for 15‐year survival , 1993, Cancer.

[52]  M. Climent,et al.  Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment. , 2001, Breast.

[53]  B. Gusterson,et al.  Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[54]  M. Dowsett,et al.  Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. , 2005, The New England journal of medicine.

[55]  I. Andrulis,et al.  Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples , 2004, Genes, chromosomes & cancer.

[56]  W. T. Beck,et al.  Antitopoisomerase drug action and resistance. , 1996, European journal of cancer.

[57]  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.

[58]  M. Cronin,et al.  A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. , 2004, The New England journal of medicine.

[59]  R. Gelber,et al.  Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer? , 2000, The Lancet.

[60]  D. Larsimont,et al.  HER-2/neu as a Predictive Marker in a Population of Advanced Breast Cancer Patients Randomly Treated Either with Single-agent Doxorubicin or Single-agent Docetaxel , 2004, Breast Cancer Research and Treatment.

[61]  M. Seoud,et al.  Effects of young age at presentation on survival in breast cancer , 2006, BMC Cancer.

[62]  C. Sotiriou,et al.  Potential predictive value of Bcl-2 for response to tamoxifen in the adjuvant setting of node-positive breast cancer. , 2004, Clinical breast cancer.

[63]  D. Huntsman,et al.  Prognostic and predictive value of topoisomerase II alpha in a randomized trial comparing CMF to CEF in premenopausal women with node positive breast cancer (NCIC CTG MA.5). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  M. Berger,et al.  Lapatinib plus capecitabine for HER2-positive advanced breast cancer. , 2006, The New England journal of medicine.

[65]  Philip Smith,et al.  Effect of c‐erbB2 and estrogen receptor status on survival of women with primary breast cancer treated with adjuvant cyclophosphamide/methotrexate/fluorouracil , 1999, International journal of cancer.

[66]  Donald E. Henson,et al.  Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases , 1989 .

[67]  Yudong D. He,et al.  A Gene-Expression Signature as a Predictor of Survival in Breast Cancer , 2002 .

[68]  S. Hilsenbeck,et al.  Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. , 2003, Journal of the National Cancer Institute.

[69]  R. Rosenfeld,et al.  Cases , 2010, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[70]  A. Ochiai,et al.  Histological characteristics of tumor in vessels and lymph nodes are significant predictors of progression of invasive ductal carcinoma of the breast: a prospective study. , 2004, Human pathology.

[71]  C. Sotiriou,et al.  p-53 gene mutations as a predictive marker in a population of advanced breast cancer patients randomly treated with doxorubicin or docetaxel in the context of a phase III clinical trial. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[72]  R. Coombes,et al.  The clinical significance of disseminated tumor cells in breast cancer , 2007, Nature Clinical Practice Oncology.

[73]  J. Kononen,et al.  Expression of topoisomerase IIalpha is associated with rapid cell proliferation, aneuploidy, and c-erbB2 overexpression in breast cancer. , 1996, The American journal of pathology.

[74]  Michael Gnant,et al.  Prognostic Value of Lymphangiogenesis and Lymphovascular Invasion in Invasive Breast Cancer , 2004, Annals of surgery.

[75]  C. Sotiriou,et al.  HER-2/neu Gene and protein in breast cancer , 2004 .

[76]  B Fisher,et al.  erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. , 1998, Journal of the National Cancer Institute.

[77]  B. Rasmussen,et al.  Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[79]  S. Ménard,et al.  Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  C. Osborne,et al.  HER-2 Amplification, HER-1 Expression, and Tamoxifen Response in Estrogen Receptor-Positive Metastatic Breast Cancer , 2004, Clinical Cancer Research.

[81]  M. J. van de Vijver,et al.  Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. , 2006, Journal of the National Cancer Institute.

[82]  S. Pepe,et al.  Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[83]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[84]  John R. Mackey,et al.  Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Docetaxel (AC→T) with Doxorubicin and Cyclophosphamide Followed by Docetaxel and Trastuzumab (AC→TH) with Docetaxel, Carboplatin and Trastuzumab (TCH) in Her2neu Positive Early Breast Cancer Patients: BCIRG 006 Study. , 2009 .

[85]  M. Dowsett,et al.  Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  J. Ross,et al.  Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[87]  C K Osborne,et al.  Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[88]  P Boracchi,et al.  Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[89]  Jens Overgaard,et al.  retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[90]  R. Veitia,et al.  Tau expression in model adenocarcinomas correlates with docetaxel sensitivity in tumour-bearing mice. , 1998, British Journal of Cancer.

[91]  A. Nobel,et al.  The molecular portraits of breast tumors are conserved across microarray platforms , 2006, BMC Genomics.