{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:34:26Z","timestamp":1764700466121},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,9,23]],"date-time":"2013-09-23T00:00:00Z","timestamp":1379894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Risk Analysis"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Few studies have focused on the different roles risk factors play in the multistate temporal natural course of breast cancer. We proposed a three\u2010state Markov regression model to predict the risk from free of breast cancer (FBC) to the preclinical screen\u2010detectable phase (PCDP) and from the PCDP to the clinical phase (CP). We searched the initiators and promoters affecting onset and subsequent progression of breast tumor to build up a three\u2010state temporal natural history model with state\u2010dependent genetic and environmental covariates. This risk assessment model was applied to a 1 million Taiwanese women cohort. The proposed model was verified by external validation with another independent data set. We identified three kinds of initiators, including the BRCA gene, seven single nucleotides polymorphism, and breast density. ER, Ki\u201067, and HER\u20102 were found as promoters. Body mass index and age at first pregnancy both played a role. Among women carrying the BRCA gene, the 10\u2010year predicted risk for the transition from FBC to CP was 25.83%, 20.31%, and 13.84% for the high\u2010, intermediate\u2010, and low\u2010risk group, respectively. The corresponding figures were 1.55%, 1.22%, and 0.76% among noncarriers. The mean sojourn time of staying at the PCDP ranged from 0.82 years for the highest risk group to 6.21 years for the lowest group. The lack of statistical significance for external validation () revealed the adequacy of our proposed model. The three\u2010state model with state\u2010dependent covariates of initiators and promoters was proposed for achieving individually tailored screening and also for personalized clinical surveillance of early breast cancer.<\/jats:p>","DOI":"10.1111\/risa.12116","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T21:52:21Z","timestamp":1381528341000},"page":"367-379","source":"Crossref","is-referenced-by-count":14,"title":["Risk Assessment of Multistate Progression of Breast Tumor with State\u2010Dependent Genetic and Environmental Covariates"],"prefix":"10.1111","volume":"34","author":[{"given":"Yi\u2010Ying","family":"Wu","sequence":"first","affiliation":[{"name":"Graduate Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Fang","family":"Yen","sequence":"additional","affiliation":[{"name":"School of Oral Hygiene Oral Medicine of College Taipei Medical University Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Ping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology Tri\u2010Service General Hospital Taipei City Taiwan"},{"name":"Department of Pathology Graduate Institute of Pathology and Parasitology National Defense Medical Center Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu\u2010Hsi","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei City 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