title: The impact of in situ breast cancer and family history on risk of subsequent breast cancer events and mortality - a population-based study from Sweden.
abstract: The clinical behavior of in situ breast cancer is incompletely understood and several factors have been associated with invasive recurrence. The purpose of this study was to evaluate long-term risk of subsequent breast cancer and mortality among women diagnosed with in situ breast cancer, in relation to family history METHODS: Using the population-based Swedish Multi-Generation and Cancer Registers we identified 8111 women diagnosed with in situ breast cancer between 1980 and 2004. We used standardized incidence ratios (SIRs) to measure the relative risk of subsequent invasive or contralateral in situ breast cancer and standardized mortality ratios (SMRs) for relative risks of death.
  
  
  
  Among women diagnosed with in situ breast cancer, the cumulative 10-year and 20-year risk for subsequent contralateral or ipsilateral invasive cancer was approximately 10 % and 18 %, respectively. The risk of subsequent invasive breast cancer was increased more than 4-fold (SIR 4.6 (95 % CI 4.2 - 4.9)) among women with in situ breast cancer as compared to women in the general population and the risk of contralateral in situ breast cancer was increased almost 16-fold (SIR 16.0 (95 % CI 13.2-19.1)). Having a family history of breast cancer increased the risk of contralateral invasive breast cancer by almost 50 % (incidence rate ratio 1.5 (95 % CI 1.0-2.0)). Women under forty years old at diagnosis, without family history, had a 7-fold increased risk, and those with a family history had a 14-fold increased risk for subsequent invasive breast cancer with SIRs of 7.2 (95 % CI 4.8-10.5) and 14.3 (95 % CI 7.4-25.0), respectively. The overall risk of death in women with in situ breast cancer was significantly increased by 30 % compared to the general population but was highly dependent on the occurrence of a second invasive cancer event (SMR 1.3 (95 % CI 1.2-1.4)).
  
  
  
  Among women with in situ breast cancer, a positive family history increases the risk of contralateral invasive breast cancer by almost 50 %. The risk of subsequent invasive breast cancer and mortality is substantially higher in younger women, which should be taken into account when planning their treatment and follow up.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. helena.ikonomidis-sackey@karolinska.se.|Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden. helena.ikonomidis-sackey@karolinska.se.
authors.forename: Helena
authors.initials: H
authors.lastname: Sackey
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Miao
authors.initials: M
authors.lastname: Hui
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Helena
authors.initials: H
authors.lastname: Verkooijen
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Gustaf
authors.initials: G
authors.lastname: Edgren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Frisell
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.|Department of Surgery, National University Hospital, Singapore, Singapore.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hartman
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000071960:Breast Carcinoma In Situ / Q000453:epidemiology*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009026:Mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D011159:Population Surveillance; D012042:Registries; D012306:Risk; D013548:Sweden / Q000453:epidemiology
keywords: Contralateral breast cancer; In situ breast cancer; Mortality; Second event