title: Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status.
abstract: Women with a family history of breast cancer are commonly offered regular clinical or mammographic surveillance from age 30. Data on the efficacy of such programmes are limited. Clinical, pathological and outcome data were recorded on all breast and ovarian cancers diagnosed within familial breast cancer surveillance programmes at collaborating centers in Norway and the UK up to the end of 2005. These have been analyzed according to the mutation status of the affected women (BRCA1+ve, BRCA2+ve or mutation-negative). Breast cancer was diagnosed in 442 patients subsequently followed for a total of 2095 years. Eighty-nine (20%) had BRCA1 mutations, 35 (8%) BRCA2 mutations and in 318 (72%) no mutation could be detected ("mut neg"). Five-year survival in BRCA1 was 73% compared to 96% in BRCA2 and 92% in mut neg (p = 0.000). Among BRCA1 mutation-carriers, 5-year survival was 67% for cases diagnosed as carcinoma in situ, 84% for node-negative invasive cancers and 58% for those with nodal involvement (p > 0.05). For BRCA2 mutation-carriers the corresponding figures were 100, 100 and 90% (p > 0.05), while for mut neg women they were 100, 97 and 71% (p = 0.03). Regular surveillance in women at increased familial risk of breast cancer is associated with a good outcome if they carry BRCA2 mutations or no detectable mutation. Carriers of BRCA1 mutations fare significantly worse, even when their tumors are diagnosed at an apparently early stage. The differences in outcome associated with different genetic causes of disease were associated with demonstrated differences in tumor biology. The findings demonstrate the outcome for genetically different breast cancers detected within a programme for early diagnosis and treatment, which is relevant to genetic counseling when women at risk have to chose between the options for preventing death from inherited breast cancer.
authors.affiliation: Section for Inherited Cancer, Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Clinical Center, Oslo, Norway. pmoller@ulrik.uio.no
authors.forename: Pal
authors.initials: P
authors.lastname: Moller
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Marta M
authors.initials: MM
authors.lastname: Reis
authors.forename: Helen
authors.initials: H
authors.lastname: Gregory
authors.forename: Elaine
authors.initials: E
authors.lastname: Anderson
authors.forename: Lovise
authors.initials: L
authors.lastname: Maehle
authors.forename: Fiona
authors.initials: F
authors.lastname: Lalloo
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: Jaran
authors.initials: J
authors.lastname: Apold
authors.forename: Neal
authors.initials: N
authors.lastname: Clark
authors.forename: Anneke
authors.initials: A
authors.lastname: Lucassen
authors.forename: C Michael
authors.initials: CM
authors.lastname: Steel
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011159:Population Surveillance; D015996:Survival Rate; D016896:Treatment Outcome