Radiotherapy-related heart damage in breast cancer patients is predicted by cutaneous telangiectasiae


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Chris Talbot1, George Tanteles1, Irene Peat1, Ahmed Osman1, Gerry McCann2, Steve Chan3, Julian Barwell1, R. Paul Symonds1

1University of Leicester, UK, 2University Hospitals of Leicester, Glenfield Hospital, UK, 3Nottingham University Hospitals NHS Trust, UK

Abstract

Background
Most breast cancer patients treated with breast conservation and patients at high risk of recurrence after mastectomy receive radiotherapy. The benefits of radiation therapy are not however complication-free. There is a spectrum of normal-tissue reactions, and as life expectancy of cancer patients improves, these are increasingly of clinical importance. The effects of radiotherapy can be divided into early/acute or late (occuring >90 days after treatment). Fibrosis, telangiectasiae and atrophy are examples of common late normal-tissue manifestations. In addition for left-sided breast cancer the heart may be in the radiation field and lead to increased risk of cardiovascular disease.

Radiotherapy late effects are heritable and amenable to genetic association studies. The TT genotype of the TGFb1 (C-509T) SNP confers a 15-fold increased risk of fibrosis after radiotherapy (p=3x10-6) compared with CC, thus confirming previous independent analyses (Giotopoulos 07). In addition alleles of the XRCC1 and eNOS genes contributed to the risk of telangiectasiae (Giotopoulos 08).

Results
We hypothesised that women showing cutaneous telangiectasiae four years after radiotherapy for breast cancer might be at increased risk of later cardiovascular disease. To test this hypothesis we searched the medical records of 153 women who had been previously scored for radiation late effects, to find evidence of heart disease. Overall 15 women had evidence of heart problems, of which 9 occurred after radiotherapy, all of whom had left-sided treatment. There was a significant correlation with occurrence of telangiectasia, with 16% of women who showed telangiectasiae having heart disease, compared with only 3% of women without telangiectasiae (OR 6.3 95% CI 1.4 28.5) (Tanteles 09).

Conclusion
This result supports the hypothesis and suggests that some women have a vascular endothelium which is genetically predisposed to radiation damage. It should now be possible to find genetic polymorphisms that predict both radiation-induced telangiectasiae and heart damage.

References
[1] Giotopoulos et al (2007) Brit J Cancer 96: 10017.
[2] Giotopoulos et al (2008) Int J Cancer 123: 29734.
[3] Tanteles et al (2009) Brit J Cancer doi:10.1038/sj.bjc.6605182