Cardiovascular Mortality After Breast Cancer Radiotherapy
Objectives This study sought to investigate long-term cardiovascular mortality and its relationship to the use of radiotherapy for breast cancer.
Background Cardiovascular diseases are among the main long-term complications of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, <20 years of follow-up.
Methods A total of 4,456 women who survived at least 5 years after treatment of a breast cancer at the Institut Gustave Roussy between 1954 and 1984 were followed up for mortality until the end of 2003, for over 28 years on average.
Results A total of 421 deaths due to cardiovascular diseases were observed, of which 236 were due to cardiac disease. Women who had received radiotherapy had a 1.76-fold (95% confidence interval [CI]: 1.34 to 2.31) higher risk of dying of cardiac disease and a 1.33-fold (95% CI: 0.99 to 1.80) higher risk of dying of vascular disease than those who had not received radiotherapy. Among women who had received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27 to 1.90) higher risk of dying of cardiac disease than those treated for a right-sided breast cancer. This relative risk increased with time since the breast cancer diagnosis (p = 0.05).
Conclusions This study confirmed that radiotherapy, as delivered until the mid-1980s, increased the long-term risk of dying of cardiovascular diseases. The long-term risk of dying of cardiac disease is a particular concern for women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy.
Breast cancer is becoming an increasingly survivable disease with a large population of long-term survivors due to advances in its diagnosis and treatment. The focus has therefore shifted to long-term treatment-related toxicity. Although randomized trials have demonstrated that breast irradiation significantly decreases the incidence of ipsilateral breast recurrences in women with either invasive or in situ breast cancer, long-term survivors may develop late cardiovascular toxicity due to the radiation dose delivered to the heart and the coronary arteries. During the second part of the 20th century, the radiation doses delivered to these structures were high; for example, it was estimated that breast or chest wall radiotherapy resulted in whole heart doses of 0.9 to 14.0 Gy for left-sided and of 0.4 to 6.0 Gy for right-sided irradiation. Internal mammary chain (IMC) radiotherapy delivered heart doses of 3 to 17 Gy and 2 to 10 Gy for left- and right-sided irradiation, respectively. With contemporary tangential breast or chest wall radiotherapy for a left-sided cancer, doses higher than 20 Gy are received to some parts of the heart in nearly one-half of the patients. Nevertheless, if tangential field borders are customized or advanced radiotherapy techniques are used (e.g., intensity modulated radiotherapy), heart doses are likely to be lower. Therefore, although radiation therapy for breast cancer has long been known to induce damage in the heart, it is still important to investigate the magnitude of the risk of cardiovascular disease following radiotherapy for breast cancer. Indeed, although the risk of cardiac disease after radiotherapy for breast cancer has been known for about 20 years, only a small number of clinical series have a sufficiently extended follow-up to fully appreciate the magnitude of this risk.
In the present article, we report on cardiovascular mortality during the long-term follow-up of a single institution cohort of 4,456 5-year survivors of breast cancer treated between 1954 and 1984 at the Institut Gustave Roussy (IGR) and followed up for 28 years on average.
Abstract and Introduction
Abstract
Objectives This study sought to investigate long-term cardiovascular mortality and its relationship to the use of radiotherapy for breast cancer.
Background Cardiovascular diseases are among the main long-term complications of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, <20 years of follow-up.
Methods A total of 4,456 women who survived at least 5 years after treatment of a breast cancer at the Institut Gustave Roussy between 1954 and 1984 were followed up for mortality until the end of 2003, for over 28 years on average.
Results A total of 421 deaths due to cardiovascular diseases were observed, of which 236 were due to cardiac disease. Women who had received radiotherapy had a 1.76-fold (95% confidence interval [CI]: 1.34 to 2.31) higher risk of dying of cardiac disease and a 1.33-fold (95% CI: 0.99 to 1.80) higher risk of dying of vascular disease than those who had not received radiotherapy. Among women who had received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27 to 1.90) higher risk of dying of cardiac disease than those treated for a right-sided breast cancer. This relative risk increased with time since the breast cancer diagnosis (p = 0.05).
Conclusions This study confirmed that radiotherapy, as delivered until the mid-1980s, increased the long-term risk of dying of cardiovascular diseases. The long-term risk of dying of cardiac disease is a particular concern for women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy.
Introduction
Breast cancer is becoming an increasingly survivable disease with a large population of long-term survivors due to advances in its diagnosis and treatment. The focus has therefore shifted to long-term treatment-related toxicity. Although randomized trials have demonstrated that breast irradiation significantly decreases the incidence of ipsilateral breast recurrences in women with either invasive or in situ breast cancer, long-term survivors may develop late cardiovascular toxicity due to the radiation dose delivered to the heart and the coronary arteries. During the second part of the 20th century, the radiation doses delivered to these structures were high; for example, it was estimated that breast or chest wall radiotherapy resulted in whole heart doses of 0.9 to 14.0 Gy for left-sided and of 0.4 to 6.0 Gy for right-sided irradiation. Internal mammary chain (IMC) radiotherapy delivered heart doses of 3 to 17 Gy and 2 to 10 Gy for left- and right-sided irradiation, respectively. With contemporary tangential breast or chest wall radiotherapy for a left-sided cancer, doses higher than 20 Gy are received to some parts of the heart in nearly one-half of the patients. Nevertheless, if tangential field borders are customized or advanced radiotherapy techniques are used (e.g., intensity modulated radiotherapy), heart doses are likely to be lower. Therefore, although radiation therapy for breast cancer has long been known to induce damage in the heart, it is still important to investigate the magnitude of the risk of cardiovascular disease following radiotherapy for breast cancer. Indeed, although the risk of cardiac disease after radiotherapy for breast cancer has been known for about 20 years, only a small number of clinical series have a sufficiently extended follow-up to fully appreciate the magnitude of this risk.
In the present article, we report on cardiovascular mortality during the long-term follow-up of a single institution cohort of 4,456 5-year survivors of breast cancer treated between 1954 and 1984 at the Institut Gustave Roussy (IGR) and followed up for 28 years on average.
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