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Abstract
The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
We observed an increased risk of leukaemia in women with a BRCA2 mutation who receive chemotherapy for breast cancer.
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