title: Estimating the number of rate limiting genomic changes for human breast cancer.
abstract: 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.
authors.affiliation: Biometric Research Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892-7434, USA.
authors.forename: Xinan
authors.initials: X
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D014481:United States / Q000453:epidemiology