title: Risk prediction for local versus regional/metastatic tumors after initial ductal carcinoma in situ diagnosis treated by lumpectomy.
abstract: Among women diagnosed with ductal carcinoma in situ (DCIS), we identified factors associated with local invasive cancer (LIC) and regional/metastatic invasive cancer (RMIC) and provide 10-year risks based on clinically relevant factors. We created a retrospective, population-based cohort of 1492 women with an initial diagnosis of DCIS (1983-1996) treated by lumpectomy alone. Histological and molecular markers (Ki67, ER, PR, COX-2, p16, ERBB2) were collected on DCIS cases with a subsequent tumor (DCIS, LIC, or RMIC) and a subsample of frequency-matched controls without subsequent tumors. Competing risks methods were used to identify factors associated with LIC and RMIC and cumulative incidence methods to estimate 10-year risks for combinations of factors. Median follow-up time was 12.6 years (range 0.5-29.5 years). The overall 10-year risk of LIC (11.9 %) was higher than for RMIC (3.8 %). About half of women with initial DCIS lesions are detected by mammography and p16 negative and have a 10-year risk of LIC of 6.2 % (95 % CI 5.8-6.8 %) and RMIC of 1.2 % (95 % CI 1.1-1.3 %). Premenopausal women whose DCIS lesion was p16 positive or p16 negative and detected by palpation had high 10-year risk of LIC of 23.0 % (95 % CI 19.3-27.4 %). Ten-year risk of RMIC was highest at 22.5 % (95 % CI 13.8-48.1 %) for those positive for p16, COX-2, and ERRB2, and negative for ER, but prevalence of this group is low at 3 %. Ten-year risk of LIC and RMIC is low for the majority diagnosed with DCIS. Combinations of molecular markers and method of detection of initial DCIS lesion can differentiate women at low and high risk of LIC and RMIC.
authors.affiliation: Departments of Neurosurgery and Epidemiology and Biostatistics, UCSF, 400 Parnassus Ave A850b, Room A 808, San Francisco, CA, 94143-0372, USA. Annette.molinaro@ucsf.edu.
authors.forename: Annette M
authors.identifier: 0000-0002-9854-7404
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Department of Medicine, UCSF, San Francisco, USA.
authors.forename: Jennette D
authors.initials: JD
authors.lastname: Sison
authors.affiliation: Department of Pathology, UCSF, San Francisco, USA.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Ljung
authors.affiliation: Department of Pathology and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, USA.
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
authors.affiliation: Departments of Medicine and Epidemiology and Biostatistics, UCSF, San Francisco, USA.|General Internal Medicine Section, Department of Veterans Affairs, UCSF, San Francisco, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery*; D005260:Female; D006801:Humans; D008327:Mammography; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Ductal carcinoma in situ; Local invasive cancer; Recurrence; Regional/metastatic invasive cancer; Risk