title: Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status.
abstract: BACKGROUND
  Management of early-stage breast cancer in young women with mutations in BRCA1 or BRCA2 remains controversial. This study assessed the long-term risks of ipsilateral and contralateral breast cancer in a cohort of young women who underwent breast-conserving surgery followed by radiotherapy.
  
  
  METHODS
  Between 1975 and 1998, 290 women with breast cancer diagnosed at age 42 years or younger underwent lumpectomy followed by radiotherapy at our hospital. We recruited 127 of these women for complete sequencing of BRCA1 and BRCA2. Demographic, clinical, pathological, and outcome data were recorded. The primary endpoints were rates of ipsilateral and contralateral breast cancer, in relation to germline BRCA1/2 status.
  
  
  RESULTS
  105 women were classified as having sporadic disease (94 with wild-type or known polymorphisms and 11 with variants of unclear significance) and 22 as having genetic predisposition (deleterious mutations in BRCA1 [15] or BRCA2 [seven]). At 12 years of follow-up, the genetic group had significantly higher rates of ipsilateral (49% vs 21%, p=0.007) and contralateral events (42% vs 9%, p=0.001) than the sporadic group. The majority of events were classified as second primary tumours. No patient in the genetic group had undergone oophorectomy or was taking prophylactic agents such as tamoxifen.
  
  
  CONCLUSIONS
  Patients with germline mutations in BRCA1 or BRCA2 have a high risk of developing late ipsilateral and contralateral second primary tumours. With breast-conserving therapy, chemoprophylaxis or other interventions to reduce the rate of second cancers may be valuable. Alternatively, bilateral mastectomy may be considered, to minimise the risk of second tumours in the breasts.
authors: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA. bruce.haffty@yale.edu
authors: Bruce G
authors: BG
authors: Haffty
authors: Elizabeth
authors: E
authors: Harrold
authors: Atif J
authors: AJ
authors: Khan
authors: Pradip
authors: P
authors: Pathare
authors: Tanya E
authors: TE
authors: Smith
authors: Bruce C
authors: BC
authors: Turner
authors: Peter M
authors: PM
authors: Glazer
authors: Barbara
authors: B
authors: Ward
authors: Daryl
authors: D
authors: Carter
authors: Ellen
authors: E
authors: Matloff
authors: Allen E
authors: AE
authors: Bale
authors: Mayra
authors: M
authors: Alvarez-Franco
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011878:Radiotherapy; D016896:Treatment Outcome
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm