title: Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy.
abstract: Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaN0) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaN0 and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaN0 patients, mutation carriers had 75% 5-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but 1 relapse occurred in the 15 who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
authors.affiliation: Section of Genetic Counselling, Department of Cancer Genetics, Norwegian Radium Hospital, Oslo, Norway. pal.moller@klinmed.uio.no
authors.forename: Pål
authors.initials: P
authors.lastname: Møller
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Neva
authors.initials: N
authors.lastname: Haites
authors.forename: Marta M
authors.initials: MM
authors.lastname: Reis
authors.forename: Hans
authors.initials: H
authors.lastname: Vasen
authors.forename: Elaine
authors.initials: E
authors.lastname: Anderson
authors.forename: C Michael
authors.initials: CM
authors.lastname: Steel
authors.forename: Jaran
authors.initials: J
authors.lastname: Apold
authors.forename: David
authors.initials: D
authors.lastname: Goudie
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: Fiona
authors.initials: F
authors.lastname: Lalloo
authors.forename: Lovise
authors.initials: L
authors.lastname: Maehle
authors.forename: Helen
authors.initials: H
authors.lastname: Gregory
authors.forename: Ketil
authors.initials: K
authors.lastname: Heimdal
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010052:Ovariectomy; D015996:Survival Rate; D013997:Time Factors