Increased Leukaemia Risk For BRCA2-Positive Breast Cancer Patients

Researchers have found a link between susceptibility to leukaemia and presence of BRCA2 mutations in women who have received chemotherapy for breast cancer

medwireNews: Women harbouring BRCA2 mutations who have a history of breast cancer have an elevated risk of developing leukaemia, especially if they have received chemotherapy for the breast cancer, suggests research published in the British Journal of Cancer.

However, researcher Steven Narod, from the Women’s College Research Institute in Toronto, Ontario, Canada, and colleagues point out that the absolute risk is “very low” and therefore they believe that “the risk of leukaemia in the BRCAmutation carriers should not influence the choice of chemotherapy to treat their breast cancer.”

During an average follow-up of 6.1 years, five of 7243 women with a mutation in either theBRCA1orBRCA2gene developed leukaemia. Of these, two had mutations in BRCA1 and three in BRCA2. All five patients had a history of breast cancer and four had received chemotherapy.

The average time from the breast cancer diagnosis to the leukaemia diagnosis was 10.2 years. There were three cases of acute myeloid leukaemia, one case of chronic lymphocytic leukaemia and one undetermined case of acute leukaemia.

The presence of BRCA1 or BRCA2 mutations alone did not significantly increase the risk of developing leukaemia compared with the general population.

But the leukaemia risk was significantly higher when the patient harboured BRCA2 mutations and also had a history of breast cancer, with a standardised incidence ratio (SIR) of 4.69.

And the risk was further exacerbated among women with BRCA2-associated breast cancer who received chemotherapy, with a significant SIR of 8.11.

By contrast, BRCA1 mutation carriers with breast cancer did not have an elevated leukaemia risk relative to the general population, even when they had received chemotherapy for the disease.

Among women treated with chemotherapy for breast cancer, the absolute risk of leukaemia was 0.55% for women with BRCA2-associated breast cancer and 0.06% for those with BRCA1-associated disease, the researchers report.

They speculate that “[o]ne potential reason why the impact of BRCA mutations on leukaemia incidence might be less than that for breast and ovarian cancer susceptibility could be that the self-renewal potential of leukaemic cells is dependent on genome stability, which is compromised when there is a BRCA mutation.”

Reference

Iqbal J, Nussenzweig A, Lubinski J, et al. The incidence of leukaemia in women withBRCA1andBRCA2mutations: an International Prospective Cohort Study.Br J Cancer2016; Advance online publication 17 March. doi: 10.1038/bjc.2016.58

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