title: Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy.
abstract: BRCA1 and BRCA2 germline mutations are associated with a strong risk of breast cancer, which may preclude breast-conserving treatment in carriers. This study examined whether mutation status influenced the rate of breast cancer recurrence following breast-conserving treatment. BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer, who had been treated with breast-conserving surgery and radiotherapy. The 131 patients with familial history were matched to 261 patients without, according to age at diagnosis and year of treatment. The follow-up of controls was at least equal to the time-interval between diagnosis and genetic testing in familial cases. Matched cohorts were compared according to rates of breast cancer recurrence as first event and contralateral breast cancer using log-rank tests. BRCA1/2 mutations were found in 20.6% patients with a family history. Nineteen patients had a BRCA1 mutation and 8 had a BRCA2 mutation. Breast cancers in mutation carriers were more often grade III (p<10-4) and oestrogen receptor negative (p=0.005) than tumours in both non-carriers and controls. Median follow-up for all 392 patients was 8.75 years. No significant differences in breast cancer recurrence as first event were seen between BRCA1/2 tumours and controls (p=0.47), carriers and non-carriers with a family history (p=0.96), or non-carriers and controls (p=0.10). On multivariate analysis, age was the most important factor significantly predicting for breast cancer recurrence. The rate of contralateral breast cancer was significantly increased in all patients with a family history: BRCA1/2 carriers versus controls (p=0.0003), non-carriers versus controls (p=0.0034) and carriers versus non-carriers (p=0.02). At a 9-year median follow-up, the rate of ipsilateral breast cancer recurrence was not higher in BRCA1 and BRCA2 mutation carriers than in non-carriers with a family history or sporadic cases. These results support the hypothesis that breast tumours in BRCA carriers are more sensitive to radiation. Therefore, breast-conserving treatment can be offered to these patients. However, longer follow-up is needed to ensure that the rate of new primary cancer in the treated breast does not increase in the long-term.
authors.affiliation: Department of Radiation Oncology, Institut Curie, 26 Rue d'Ulm, 75248 Paris, Cedex 05, France. youlia.kirova@curie.net
authors.forename: Youlia M
authors.initials: YM
authors.lastname: Kirova
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Alexia
authors.initials: A
authors.lastname: Savignoni
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fabre
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D004812:Epidemiologic Methods; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods