TP53 and breast cancer

The TP53 gene (p53) is found altered in breast carcinomas in approximately 20–40% of all cases depending on tumor size and stage of the disease. It seems to be an early event in breast tumorigenesis. Several polymorphisms in the TP53 gene have been detected and their possible roles in breast cancer risk and association to type of cancer developed are discussed. The different mutation spectra seen in geographical and ethnic populations may be used to identify environmental exposure contributing to breast cancer development. The role of TP53 mutation as a prognostic marker is reviewed as well as its role as a predictor for therapy response. All data available on TP53 mutation analyses of human breast carcinomas, as well data from transgenic animal studies and experimental cell studies, support an important role for TP53 in mammary carcinogenesis. Hum Mutat 21:292–300, 2003. © 2003 Wiley‐Liss, Inc.

[1]  P. Borgen,et al.  In microdissected ductal carcinoma in situ, HER‐2/neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology , 2000, Cancer.

[2]  Christian A. Rees,et al.  Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[3]  A. Levine,et al.  Poor prognosis of p53 gene mutation and nuclear overexpression of p53 protein in inflammatory breast carcinoma. , 1993, Journal of the National Cancer Institute.

[4]  M. Olivier,et al.  TP53 mutation patterns in breast cancers: searching for clues of environmental carcinogenesis. , 2001, Seminars in cancer biology.

[5]  D. Schaid,et al.  Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  V. Chen,et al.  Racial disparity in the association of p53 gene alterations with breast cancer survival. , 1995, Cancer research.

[7]  J. Eyfjörd,et al.  TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material. , 1996, British Journal of Cancer.

[8]  B. O’Malley,et al.  p53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Thierry Soussi,et al.  Assessing TP53 status in human tumours to evaluate clinical outcome , 2001, Nature Reviews Cancer.

[10]  E. Hovig,et al.  TP53 mutations and breast cancer prognosis: Particularly poor survival rates for cases with mutations in the zinc‐binding domains , 1995, Genes, chromosomes & cancer.

[11]  Joe W. Gray,et al.  Quantitative analysis of chromosomal CGH in human breast tumors associates copy number abnormalities with p53 status and patient survival , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Foekens,et al.  Prognostic significance of TP53 accumulation in human primary breast cancer: Comparison between a rapid quantitative immunoassay and SSCP analysis , 1996, International journal of cancer.

[13]  M. Redston,et al.  p53 missense mutations in microdissected high-grade ductal carcinoma in situ of the breast. , 2001, Journal of the National Cancer Institute.

[14]  S. Fuqua,et al.  The role and prognostic significance of p53 gene alterations in breast cancer , 2004, Breast Cancer Research and Treatment.

[15]  J. Eyfjord,et al.  GSTM1, GSTT1, and GSTP1 genotypes in relation to breast cancer risk and frequency of mutations in the p53 gene. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[16]  M. Inganäs,et al.  Prognostic value of P53 gene mutations in a large series of node-negative breast cancer patients. , 1998, Cancer research.

[17]  L. Strong,et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. , 1990, Science.

[18]  B. Iacopetta,et al.  Analysis of p53 gene mutation by polymerase chain reaction-single strand conformation polymorphism provides independent prognostic information in node-negative breast cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  B. Iacopetta,et al.  Detection of p53 gene mutation by rapid PCR‐SSCP and its association with poor survival in breast cancer , 1997, International journal of cancer.

[20]  M. Wolff,et al.  Waf-1 (p21) and p53 polymorphisms in breast cancer. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[21]  J. Foekens,et al.  Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. , 1998, British Journal of Cancer.

[22]  Genetic profiling of breast cancer: from molecular portraits to clinical utility. , 2003, The International journal of biological markers.

[23]  Thierry Soussi,et al.  The UMD‐p53 database: New mutations and analysis tools , 2003, Human mutation.

[24]  A. Hartmann,et al.  The molecular epidemiology of p53 gene mutations in human breast cancer. , 1997, Trends in genetics : TIG.

[25]  B. Ponder,et al.  A Systematic Review Of Genetic Polymorphisms and Breast Cancer Risk 1 , 2000 .

[26]  J. Eyfjörd,et al.  TP53 mutations and abnormal p53 protein staining in breast carcinomas related to prognosis. , 1995, European journal of cancer.

[27]  Toshihide Tsuda,et al.  The TP53 gene, tobacco exposure, and lung cancer , 2003, Human mutation.

[28]  I. Andrulis,et al.  p53 Protein Accumulation in Non-Invasive Lesions Surrounding p53 Mutation Positive Invasive Breast Cancers , 2004, Breast Cancer Research and Treatment.

[29]  T. Crook,et al.  TP53 mutations in familial breast cancer: Functional aspects , 2003, Human mutation.

[30]  C Béroud,et al.  p53 Website and analysis of p53 gene mutations in human cancer: Forging a link between epidemiology and carcinogenesis , 2000, Human mutation.

[31]  D. Evans,et al.  A detailed study of loss of heterozygosity on chromosome 17 in tumours from Li – Fraumeni patients carrying a mutation to the TP53 gene , 1997, Oncogene.

[32]  S. Hirohashi,et al.  A prospective study of the significance of gene and chromosome alterations as prognostic indicators of breast cancer patients with lymph node metastases , 1998, Breast Cancer Research and Treatment.

[33]  D. Horsfall,et al.  Relationship between p53 gene abnormalities and other tumour characteristics in breast‐cancer prognosis , 1996, International journal of cancer.

[34]  L. Holmberg,et al.  p53 Status predicts survival in breast cancer patients treated with or without postoperative radiotherapy: a novel hypothesis based on clinical findings. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  Thierry Soussi,et al.  P53 Gene Mutation: Software and Database , 1996, Nucleic Acids Res..

[36]  A. Børresen-Dale,et al.  Single tube multiplex polymerase chain reaction genotype analysis of GSTM1, GSTT1 and GSTP1: relation of genotypes to TP53 tumor status and clinicopathological variables in breast cancer patients. , 1998, Pharmacogenetics.

[37]  D. Schaid,et al.  p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis. , 1994, Oncogene.

[38]  T. Aas,et al.  Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients , 1996, Nature Medicine.

[39]  B. Iacopetta,et al.  Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[40]  K. Vähäkangas.  TP53 mutations in workers exposed to occupational carcinogens , 2003, Human mutation.

[41]  J. Ferlay,et al.  Globocan 2000 : cancer incidence, mortality and prevalence worldwide , 2001 .

[42]  J. Cunningham,et al.  A prospective trial of midwest breast cancer patients: A p53 gene mutation is the most important predictor of adverse outcome , 2000, International journal of cancer.

[43]  Z. Shao,et al.  p53 mutation in plasma DNA and its prognostic value in breast cancer patients. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[44]  C Caldas,et al.  Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis , 1999, British Journal of Cancer.

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

[46]  L. Holmberg,et al.  Increased p53 mutation frequency during tumor progression--results from a breast cancer cohort. , 2001, Cancer research.

[47]  A. Børresen,et al.  Alterations of the TP53 gene as a potential prognostic marker in breast carcinomas. Advantages of using constant denaturant gel electrophoresis in mutation detection. , 1995, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[48]  E. Berns,et al.  Prognostic value of TP53 gene mutation in adjuvant treated breast cancer patients , 2001, Breast Cancer Research and Treatment.

[49]  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.

[50]  H. J. Evans,et al.  p53 mutations in breast cancer. , 1992, Cancer research.

[51]  R. Vossen,et al.  Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer. , 2000, Cancer research.

[52]  J. Eyfjörd,et al.  Somatic p53 mutations in human breast carcinomas in an Icelandic population: a prognostic factor. , 1993, Cancer research.

[53]  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.

[54]  R. Millikan,et al.  Prevalence and spectrum of p53 mutations associated with smoking in breast cancer. , 2002, Cancer research.

[55]  L. Holmberg,et al.  Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy , 1995, Nature Medicine.

[56]  P. Guldberg,et al.  Heterogeneity in the clinical phenotype of TP53 mutations in breast cancer patients , 2000, Breast Cancer Research.

[57]  T. Aas,et al.  Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. , 2001, Cancer research.

[58]  S. Sommer,et al.  p53 As a mutagen test in breast cancer , 2002, Environmental and molecular mutagenesis.

[59]  M. Gnant,et al.  Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients. Austrian Breast Cancer Study Group. , 1999, European journal of cancer.

[60]  P. Lønning,et al.  The TP53 codon 72 polymorphism may affect the function of TP53 mutations in breast carcinomas but not in colorectal carcinomas. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[61]  J. Overgaard.  TP53 Mutation is an Independent Prognostic Marker for Poor Outcome in Both Node-negative and Node-positive Breast Cancer , 2000, Acta oncologica.

[62]  J. Bergh,et al.  Comparison between p53 protein measurements using the luminometric immunoassay and immunohistochemistry with detection of p53 gene mutations using cDNA sequencing in human breast tumors , 1998, International journal of cancer.

[63]  W. Dupont,et al.  P53 gene mutations and steroid receptor status in breast cancer. Clinicopathologic correlations and prognostic assessment , 1994, Cancer.

[64]  P. Chappuis,et al.  TP53 mutations in breast cancer associated with BRCA1 or BRCA2 germ-line mutations: distinctive spectrum and structural distribution. , 2001, Cancer research.

[65]  E. Berns,et al.  Associations between common polymorphisms in TP53 and p21WAF1/Cip1 and phenotypic features of breast cancer. , 2002, Carcinogenesis.

[66]  K. Heimdal,et al.  Prognostic significance of TP53 alterations in breast carcinoma. , 1993, British Journal of Cancer.

[67]  C. Harris,et al.  The IARC TP53 database: New online mutation analysis and recommendations to users , 2002, Human mutation.

[68]  J. Eyfjörd,et al.  Genomic instability and poor prognosis associated with abnormal TP53 in breast carcinomas. Molecular and immunohistochemical analysis , 1997, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[69]  R. Albano,et al.  TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: Association with risk factors and tumor characteristics , 2002, International journal of cancer.