Estimating the number of rate limiting genomic changes for human breast cancer

We used multistage models that incorporate the age dependent dynamics of normal breast tissue, clonal expansion of intermediate cells and mutational events to fit data for the age-specific incidence of breast cancers in the surveillance, epidemiology, and end results (SEER) registry. Our results suggest that two or three rate limiting events occurring at rates characteristic of point mutation rates for normal mammalian cells set in motion a sequence of other genomic changes that lead with high probability to breast carcinoma.

[1]  L. Loeb,et al.  A mutator phenotype in cancer. , 2001, Cancer research.

[2]  L. Norton,et al.  Growth curve of an experimental solid tumor following radiotherapy. , 1977, Journal of the National Cancer Institute.

[3]  L. Loeb.  Microsatellite Instability: Marker of a Mutator Phenotype in Cancer , 1994 .

[4]  K. Kinzler,et al.  Genetic instability in colorectal cancers , 1997, Nature.

[5]  A. Balmain,et al.  How many mutations are required for tumorigenesis? implications from human cancer data , 1993 .

[6]  G. Steel,et al.  Growth kinetics of tumours : cell population kinetics in relation to the growth and treatment of cancer , 1977 .

[7]  L. Loeb,et al.  Errors in DNA replication as a basis of malignant changes. , 1974, Cancer research.

[8]  P. Armitage,et al.  The Age Distribution of Cancer and a Multi-stage Theory of Carcinogenesis , 1954, British Journal of Cancer.

[9]  P. Hartge,et al.  The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. , 1997, The New England journal of medicine.

[10]  Robert DeMars,et al.  The spontaneous azaguanine-resistant mutants of diploid human fibroblasts , 2004, Humangenetik.

[11]  Radmacher,et al.  RESPONSE: re: estimation of Tamoxifen's efficacy for preventing the formation and growth of breast tumors , 2000, Journal of the National Cancer Institute.

[12]  L. Loeb,et al.  Mutator phenotype may be required for multistage carcinogenesis. , 1991, Cancer research.

[13]  K. Loeb,et al.  Multiple mutations and cancer , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W F Bodmer,et al.  The mutation rate and cancer. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Koller,et al.  BRCA1 required for transcription-coupled repair of oxidative DNA damage. , 1998, Science.

[16]  Ian Tomlinson,et al.  Selection, the mutation rate and cancer: Ensuring that the tail does not wag the dog , 1999, Nature medicine.

[17]  Spratt Js,et al.  Assessing the risk of breast cancer. , 2000 .

[18]  A. Knudson.  Mutation and cancer: statistical study of retinoblastoma. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[19]  W. Bodmer,et al.  How many mutations in a cancer? , 2002, The American journal of pathology.

[20]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[21]  S H Moolgavkar,et al.  Two-stage model for carcinogenesis: Epidemiology of breast cancer in females. , 1980, Journal of the National Cancer Institute.