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17-03-2016 | Hematologic cancers | Article

British Journal of Cancer

The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study

Authors: Javaid Iqbal, Andre Nussenzweig, Jan Lubinski, Tomasz Byrski, Andrea Eisen, Louise Bordeleau, Nadine M Tung, Siranoush Manoukian, Catherine M Phelan, Ping Sun, Steven A Narod, The Hereditary Breast Cancer Research Group

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Abstract

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.

Br J Cancer 2016; 114: 1160–1164. doi:10.1038/bjc.2016.58

Germline mutations in the BRCA1 and the BRCA2 genes increase the susceptibility for a woman to develop breast and ovarian cancer (Miki et al, 1994; Wooster et al, 1995). Women with an inherited mutation in the BRCA1 or the BRCA2 gene have a life-time risk of ~70% of developing breast cancer (Claus et al, 1996; Ford et al, 1998; Antoniou et al, 2003; Chen and Parmigiani, 2007; Mavaddat et al, 2013). Reports from the Breast Cancer Linkage Consortium suggested that women with BRCA1 and BRCA2 mutations have elevated risk of cancers other than breast and ovarian cancers (The Breast Cancer Linkage Consortium, 1999; Thompson et al, 2002). However, it is not clear to what extent a mutation in BRCA genes affects the risk of leukaemia.

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