Prediction of hot flushes in women taking tamoxifen for breast cancer prevention

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Published: 5 Oct 2020
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Michael Hale - Queen Mary University, London, UK

Michael Hale speaks to ecancer about the study presented at EBCC-12 that investigates the association of genetic variations for prediction of hot flushes in women taking tamoxifen for breast cancer prevention.

In this interview he first speaks about the aims and objectives of this study and then goes on to explain how tamoxifen and genetic variations can cause hot flushes in women. Michael talks about how women take tamoxifen for prevention of breast cancer and why it is important to investigate the side effects of this drug.

He further goes on to explain the results of this study and concludes with highlighting how the results from this study can be used by doctors and patients alike to decide whether taking tamoxifen is the best course of action for preventative therapy.

 

SNPs have often been linked, associated, with breast cancer risk but very few people have looked at whether they are associated with side effects of the cancer drugs that we use for prevention. So they are tamoxifen or aromatase inhibitors. The aims of the study were to see just that, to see whether single nucleotide polymorphisms are associated with hot flushes in the early stages of taking tamoxifen for breast cancer prevention and looking at both single SNPs and then seeing if we can combine multiple SNPs into a model that can then be used to predict side effect risk.

How is the use of tamoxifen and genetic variations associated with hot flushes in women?

The IBIS-1 trial is a trial of women who have been randomised to either tamoxifen or placebo for five years and we see that tamoxifen decreases the risk of breast cancer but increases the risk of hot flushes. So what we were looking at was do SNPs… is there a genetic basis for why women might react differently with tamoxifen so therefore increasing the risk of hot flushes or are SNPs not associated with side effects at all. So that was what we were investigating – what is the exact nature of the association between SNPs and the hot flushes.

What were the results of this study?

We did both single and multi-SNP investigations. The results of the single SNP investigation showed that no SNPs were statistically significantly associated with hot flushes. Then within the multi-SNP modelling we identified four SNPs that had a weak association with hot flushes. We took those four and we created a PRS model, which is a polygenic risk score with the aim of looking at whether a woman’s risk is altered depending on where they fall on that scale. We found that women who came towards the top end had about a twofold increase in risk over the middle quintile and those at the lowest end had about a 50% reduction in hot flush risk.

How can this study impact the future of breast cancer prevention therapy?

We hope that, particularly using the multigenic model, that if that model can be validated in a larger and independent cohort that the PRS could help clinicians and patients make an informed decision on the medication and to identify women who might be at higher risk of side effects which is often given as one of the major reasons women don’t want to take tamoxifen.