title: Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience.
abstract: BACKGROUND
  Breast cancer (BC) detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification.
  
  
  METHODS
  We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44) were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC). The standardized incidence ratio (SIR) was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided.
  
  
  RESULTS
  After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI) = 1.6 to 7.6; p < 0.001]. The incidence observed among BRCA carriers (SIR = 20.3; 95% CI = 3.1 to 83.9; P < 0.001), women at increased (SIR = 4.5; 95% CI = 1.5 to 8.3; P < 0.001) or intermediate risk (SIR = 7.0, 95% CI = 2.0 to 17.1; P = 0.0018) was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74).
  
  
  CONCLUSIONS
  The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in the slightly increased risk group. These results support the effectiveness of the proposed program to identify and monitor individuals at high risk, whereas prospective trials are needed for women belonging to families with sporadic BC or OC.
authors.affiliation: Centro per lo Studio dei tumori familiari, Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Italy. hbc@unimo.it
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
authors.forename: Daniela
authors.initials: D
authors.lastname: Turchetti
authors.forename: Isabella
authors.initials: I
authors.lastname: Marchi
authors.forename: Antonella
authors.initials: A
authors.lastname: Fracca
authors.forename: Barbara
authors.initials: B
authors.lastname: Canossi
authors.forename: Battista
authors.initials: B
authors.lastname: Rachele
authors.forename: Ruscelli
authors.initials: R
authors.lastname: Silvia
authors.forename: Pecchi Anna
authors.initials: PA
authors.lastname: Rita
authors.forename: Torricelli
authors.initials: T
authors.lastname: Pietro
authors.forename: Federico
authors.initials: F
authors.lastname: Massimo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1 / Q000502:physiology; D024522:Genes, BRCA2 / Q000502:physiology; D005820:Genetic Testing / Q000379:methods; D005828:Genetics, Population / Q000706:statistics & numerical data; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D016019:Survival Analysis; D016217:Ultrasonography, Mammary / Q000379:methods