title: Estrogen receptor status in CHEK2-positive breast cancers: implications for chemoprevention.
abstract: To investigate the relationship between CHEK2 mutation status and estrogen receptor (ER) status in unselected cases of early-onset breast cancer from Poland, we screened 4441 women diagnosed with breast cancer younger than 51 years and 7217 controls for three inherited mutations in CHEK2 (1100delC, IVS2+1G>A, del5395). ER status was compared between CHEK2-positive and CHEK2-negative breast cancer cases. A truncating mutation in CHEK2 was seen in 140 of 4441 cases and in 70 of 7217 controls [odds ratio (OR) = 3.3; 95% CI = 2.5-4.4; p < 0.0001]. ER status was available for 92 of 140 mutation carriers and for 3001 of 4301 non-carriers with breast cancer. The OR was higher for ER-positive cancers (OR = 3.9; 95% CI = 2.7-5.4; p < 0.0001) than for ER-negative cancers (OR = 2.1; 95% CI = 1.3-3.3; p = 0.002). Sixty-six of the 92 breast cancers in carriers of CHEK2 truncating mutations were ER positive compared with 1742 of the 3001 breast cancers in non-carriers (72% vs 58%; p = 0.01). Women with a CHEK2 mutation face a fourfold increase in the risk of ER-positive breast cancer and might be candidates for tamoxifen chemoprevention.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland. cezarycy@sci.pam.szczecin.pl
authors.forename: C
authors.initials: C
authors.lastname: Cybulski
authors.forename: T
authors.initials: T
authors.lastname: Huzarski
authors.forename: T
authors.initials: T
authors.lastname: Byrski
authors.forename: J
authors.initials: J
authors.lastname: Gronwald
authors.forename: T
authors.initials: T
authors.lastname: Debniak
authors.forename: A
authors.initials: A
authors.lastname: Jakubowska
authors.forename: B
authors.initials: B
authors.lastname: Górski
authors.forename: D
authors.initials: D
authors.lastname: Wokołorczyk
authors.forename: B
authors.initials: B
authors.lastname: Masojć
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: J
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D064447:Checkpoint Kinase 2; D018890:Chemoprevention; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011044:Poland / Q000453:epidemiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases