title: The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study.
abstract: Germline mutations in BRCA1 and BRCA2 increase the susceptibility to develop breast and ovarian cancers as well as increase the risk of some other cancers. Primary objective was to estimate the risk of leukaemia in BRCA1 and BRCA2 mutation carriers.
  
  
  
  We followed 7243 women with a BRCA1 or a BRCA2 mutation for incident cases of leukaemia. We used the standardised incidence ratio (SIR) to estimate the relative risk of leukaemia, according to mutation and history of breast cancer.
  
  
  
  We identified five incident cases of leukaemia (two BRCA1, three BRCA2). All five women had a prior history of breast cancer and four had received chemotherapy. The mean time from breast cancer diagnosis to the development of leukaemia was 10.2 years (range 3-18 years). The SIR for BRCA1 carriers was 0.66 (95% CI: 0.11-2.19, P=0.61) and the SIR for BRCA2 carriers was 2.42 (95% CI: 0.61-6.58, P=0.17). The SIR was significantly higher than expected for women with a BRCA2 mutation and breast cancer (SIR=4.76, 95% CI:1.21-12.96, P=0.03), in particular for women who received chemotherapy (SIR=8.11, 2.06-22.07, P=0.007).
  
  
  
  We observed an increased risk of leukaemia in women with a BRCA2 mutation who receive chemotherapy for breast cancer.
authors.affiliation: Women's College Research Institute, Familial Breast Cancer Research, Toronto, ON M5G 1N8 Canada.
authors.forename: Javaid
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda MD 20892 USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Nussenzweig
authors.affiliation: International Hereditary Cancer Center, Pomeranian Medical University, 70-111 Szczecin, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.affiliation: International Hereditary Cancer Center, Pomeranian Medical University, 70-111 Szczecin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.affiliation: Sunnybrook Regional Cancer Centre, Toronto, ON M4N3 M5 Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Eisen
authors.affiliation: Juravinksi Cancer Centre, Hamilton ON L8V 5C2 Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Bordeleau
authors.affiliation: Beth Israel Deaconess Medical Center, Cancer Risk and Prevention Program, Boston, MA 02215, USA.
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Tung
authors.affiliation: Department of Preventive and Predictive Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33647, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phelan
authors.affiliation: Women's College Research Institute, Familial Breast Cancer Research, Toronto, ON M5G 1N8 Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Women's College Research Institute, Familial Breast Cancer Research, Toronto, ON M5G 1N8 Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human