RACE
to Karolinska Institutet

Publications

This study is still in the data collection phase. Therefore, we have not yet published any papers that present the results of the study. The following papers, in which the RACE partners were involved, address the aims of RACE:

Taylor CW, McGale P, Darby SC. Cardiac risks of breast cancer radiotherapy – a contemporary view. Clin Oncol 2006;18:236-46.

This is a review of the published literature on this subject.  Early Breast Cancer Trialists' Collaborative Group. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366: 2087-106.This paper presents the results of randomised trials of radiotherapy in early breast cancer. It is mostly about the effect of radiotherapy on breast cancer itself, but Table 4 shows the findings for second cancers (other than breast cancer) and for mortality from other causes. This randomised evidence gives a rate ratio of 1.27 (with SE 0.07) for heart disease in women given radiotherapy compared with women not given radiotherapy, ie a substantial and highly significant increase.

McGale P and Darby SC. A dose–response relationship for radiation-induced heart disease—current issues and future prospects. International Journal of Epidemiology (in press). Advance access available on: doi:10.1093/ije/dyn067

The randomised trials contain only a limited amount of information on radiation-induced heart disease. Therefore it is desirable to find additional sources of information over and above the data from the trials. One source of information on heart disease in women with breast cancer is cancer registry data, in which heart disease mortality rates can be compared women with breast cancer who were and were not irradiated.  However, as is shown in Table 2 of this paper, such a comparison gives information about which type of women are selected for radiotherapy rather than about the effects of radiotherapy [rate ratios of 1.41 (95% CI 1.34-1.48) irradiated versus not for women given mastectomy and 0.53 (95% CI 0.47-0.58) for women given breast conserving surgery].  Table 1 of this paper shows that observational studies of radiation-induced heart disease in other circumstances have led to a wide range of conclusions. This suggests that such studies are highly prone to bias.

Darby S, McGale P, Peto R, Granath F, Hall P, Ekbom A. Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90 000 Swedish women. BMJ 2003; 326: 256-7.

Darby SC, McGale P, Taylor CW, Peto R. Long-term mortality from heart diseaseand lung cancer after radiotherapy for early breast cancer: prospective study ofabout 300 000 women in US SEER cancer registries. Lancet Oncol 2005; 6:557-65.

The biases that arise when comparing heart disease rates in irradiated and unirradiated breast cancer patients can be avoided by making use of the fact that the radiation dose to the heart from radiotherapy for breast cancer is usually higher in left-sided than in right-sided breast cancer.  It can also be demonstrated that, until recently, the laterality of the cancer was not taken into account when deciding whether or not to give radiotherapy.  Therefore, as the laterality of the breast cancer is essentially a random event, information derived from analyses comparing mortality in irradiated women with left-sided and right-sided breast cancer, such as those being carried out in the RACE project, are free of bias and carry similar weight to randomised data. 

Taylor CW, Nisbet A, McGale P, Darby SC. Cardiac exposures in breast cancer radiotherapy: 1950s-1990s. Int J Radiat Oncol Biol Phys 2007; 69:1484-1495.

In order to derive a dose-response relationship for radiation-induced heart disease, it is necessary to estimate the cardiac dose to each woman under study. This paper develops the methodology to do this.

Taylor CW, Povall J, McGale P, Nisbet A, Dodwell D, Smith JT, Darby SC. Cardiac dose from tangential breast cancer radiotherapy in the year 2006.  J Radiat Oncol Biol Phys (in press). Advance access available on: doi:10.1016/j.ijrobp.2007.12.058

Cardiac doses from breast cancer radiotherapy have decreased over the last few decades.  However, in a large radiotherapy centre in the UK, the mean dose to the heart was 2.3 Gy for women receiving tangential for left-sided breast cancer in 2006 , and part of the heart still received >20 Gy for approximately half of left-sided patients. The RACE study should provide insight into the effect of doses of this magnitude on the long-term risk of heart disease.

 

 

 

 

 

 

 

 

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