Lani
10-08-2007, 01:40 PM
Increased CV Risk in Breast Cancer Patients Examined
October 8, 2007 — The increased risk of cardiovascular disease in women who have received treatment for breast cancer is examined in a new review paper in the October 9, 2007 issue of the Journal of the American College of Cardiology.[1]
The authors, led by Dr Lee Jones (Duke University Medical Center, Durham, NC), explain that the risk of cardiovascular disease in women who have received treatment for breast cancer is increased in many different ways. "Cardiovascular clinicians need to understand this risk, and diagnostic, preventive, and/or therapeutic strategies that effectively address this need are urgently required," they say.
Jones et al note that breast cancer is the most common malignancy in American women, with approximately 213 000 new cases diagnosed in 2006. Although the incidence of breast cancer has increased by 0.2% per year between 1997 and 2000, improvements in detection and therapy have resulted in significant survival gains, with breast cancer-specific mortality decreasing almost 24% between 1990 and 2000. As a result, approximately 2.3 million American women are now living with a previous history of breast cancer, with sufficient survival to be at risk for cardiovascular disease.
The authors report that many of the chemotherapeutic agents used in breast-cancer management are associated with acute and long-term cardiac complications. Anthracycline-containing regimens are well recognized to trigger dose-dependent, cumulative, progressive cardiac dysfunction, manifested as decreased left ventricular ejection fraction (LVEF) and, ultimately, symptomatic congestive heart failure; radiotherapy also causes adverse cardiac events.
They point out that while endocrine therapy has not been clearly associated with cardiovascular injury, the new aromatase inhibitors have been associated with more cardiovascular events than tamoxifen, albeit a slightly lower incidence of thromboembolic events. Thus, longer-term follow-up is required to fully assess the associated cardiovascular risks.
In addition, the human epidermal growth factor receptor-2 (HER-2)-directed treatment of trastuzumab (Herceptin, Genentech) is associated with a heart-failure incidence of between 2.0% and 4.1% and asymptomatic cardiac dysfunction rates of between 3.0% and 18.0%; angiogenesis inhibitors are also known to be associated with cardiovascular complications, with reports of arterial thromboembolic events, increase in cardiac troponin, reductions in LVEF, and, most commonly, hypertension.
Jones et al also note that unfavorable lifestyle changes also come into the equation. "Physical activity and body weight are 2 major independent risk factors for cardiovascular disease that are often neglected when evaluating cardiovascular consequences of breast cancer therapy. It has been reported that, on average, early breast cancer patients decreased their physical activity by two hours per week from before to after diagnosis. Furthermore, more than 70% of breast-cancer patients gain between 2.5 to 6.2 kg of body weight during treatment," they write.
And to complicate matters still further, Jones et al explain that the presence of preexisting cardiovascular risk factors is itself a strong predictor for the development of breast-cancer-therapy-induced cardiovascular injury, making the likely lifetime risk for cardiovascular disease much greater. "Recent estimates suggest that physical inactivity confers a risk of breast cancer among white women of 2% to 15%, with overweight and obesity being associated with a 34% and 63% increased breast-cancer risk, respectively. It could be speculated, therefore, that physical inactivity and obesity rates may be even greater among early breast-cancer patients that, in turn, may translate into greater cardiovascular disease risk independent of the effects of adjuvant therapy."
Multiple-hit hypothesis
The authors refer to all these different causes of increased cardiovascular risk in breast-cancer survivors as the "multiple-hit" hypothesis. "We speculate that the consequences of the 'multiple hit' will become an increasingly important issue in the management of women with early breast cancer. Overall, this information is of critical importance to cardiovascular physicians, who will increasingly be called upon to evaluate and treat these women," they write.
Jones et al say that although the current and future consequences of the "multiple-hit" hypothesis will be clinically devastating, it is currently not possible to predict which patients are at increased risk of late-occurring cardiovascular disease. As current monitoring techniques (eg, echocardiography, radionuclide angiography) have limited ability to detect early cardiac damage, newer, more sensitive imaging modalities (single-photon-emission computed tomography, magnetic resonance imaging (MRI), exercise or dobutamine stress testing) as well as novel biochemical markers (brain natriuretic peptide, troponin I) that allow more accurate detection and quantification of subclinical cardiac damage are being explored, they add.
They recommend that a formal baseline cardiovascular risk assessment, using either Framingham or Reynolds risk scores, be performed before adjuvant therapy for breast cancer. "All women should be counseled about the value of a healthy lifestyle, and a program of individualized primary prevention should be undertaken as described in the American Heart Association guidelines. Unfavorable risk factors should be managed, ideally before the initiation of adjuvant therapy. Consideration should be given to more aggressive management of risk factors than might otherwise be indicated, in view of the 'multiple-hit' hypothesis presented here, although further research would be required before making such a recommendation universal," they conclude.
Source
Jones LW, Haykowsky M, Swartz JJ, et al. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007;50:1435-1441. Published online October 3, 2007.
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Clinical Context
Breast cancer is the most common malignancy in US women, with 213,000 new cases diagnosed in 2006 and incidence increasing by 0.2% per year, but mortality from breast cancer has fallen 24% between 1990 and 2000 with increasing numbers of survivors. Women living with breast cancer may be at increased risk for cardiovascular disease because of the risks associated with chemotherapy, hormonal therapy, and radiation as well as underlying cardiovascular risks.
This is a review of current therapies for breast cancer treatment and cardiovascular risk factors in women, to examine strategies for reducing the risk for cardiovascular disease among survivors of breast cancer.
Study Highlights
According to the Framingham data, women have a 39% lifetime risk for cardiovascular disease at age 50 years, with 40% having at least 1 preexisting risk factor and 17% with 2 or more risk factors.
Diabetes confers a risk for cardiovascular disease in 57% in women aged 50 to 75 years.
Risk factors for breast cancer include physical inactivity with a population-attributable risk for 2% to 15%, with overweight and obesity contributing a 34% to 63% increase in risk.
62% of patients with breast cancer are overweight or obese, and 36% are sedentary, similar to the general US female population.
Cardiovascular effects may be seen with polychemotherapy, radiotherapy, endocrine therapy, HER-2-directed therapies, and angiogenesis inhibition.
A formal baseline cardiovascular disease risk assessment before treatment for breast cancer with either Framingham or Reynolds risk scores is recommended.
Both acute and long-term cardiovascular effects are seen with anthracycline-containing regimens (doxorubicin, epirubicin), manifested as cumulative, progressive cardiac dysfunction with decreased LVEF leading to congestive heart failure.
Adjuvant trials have demonstrated left ventricular dysfunction in 10% to 50% of those receiving anthracycline-based therapies, which make patients more susceptible to long-term cardiovascular events.
Radiation has been associated for 18 years with 63 excess cases per 10,000 patient-years of cardiovascular events vs no radiation.
Radiation to either the left or right side of the chest is associated with increased risk for cardiovascular disease, lung fibrosis, and pulmonary disorders, but modern techniques provide lower risks for cardiovascular disease.
15-year cardiovascular mortality has been reported as higher for left-sided vs right-sided tumors (13% vs 10%).
Traditional endocrine therapy (tamoxifen, oophorectomy) is associated with an increased risk for venous thromboembolism and use of aromatase inhibitors with higher cardiovascular events.
HER-2-directed therapies are associated with incidence of heart failure of 2% to 4% and incidence of asymptomatic cardiac dysfunction of 3% to 18%.
Angiogenesis inhibitors (bevacizumab, sorafenib, sunitinib) and newer vascular-disrupting agents (ZD6126, TZT-1027) are reported to be associated with arterial thromboembolism.
Patients with breast cancer tend to decrease physical activity by 2 hours per week from before to after diagnosis.
More than 70% of patients with breast cancer gain 2.5 to 6.2 kg of weight during adjuvant therapy.
The multiple-hit hypothesis suggests that treatment regimens used for breast cancer increase the underlying cardiovascular risks and increase cardiovascular mortality.
It is not currently known whether treatment of risk factors modifies incidence of cardiovascular disease among women with breast cancer.
The study authors recommended that the American Heart Association guidelines for healthy lifestyle be adopted to prevent cardiovascular disease and preserve left ventricular function.
Initial treatment of hypertension should include optimal lifestyle behaviors, beta-blockers, and angiotensin-converting enzyme inhibitors with thiazides using step care.
Statins are recommended for hyperlipidemia and sulfonylurea and biguanides for type 2 diabetes.
Some agents may also have antitumor activity.
Exercise training has been shown to improve exercise capacity in survivors of breast cancer and reduced all-cause mortality.
More aggressive management of the risk for cardiovascular disease is recommended in survivors of breast cancer based on the multiple-hit hypothesis.
Pearls for Practice
Breast cancer chemotherapy and radiation are associated with the increased risk for left ventricular dysfunction, heart failure, and cardiovascular mortality.
Aggressive management following American Heart Association guidelines is recommended for survivors of breast cancer.
October 8, 2007 — The increased risk of cardiovascular disease in women who have received treatment for breast cancer is examined in a new review paper in the October 9, 2007 issue of the Journal of the American College of Cardiology.[1]
The authors, led by Dr Lee Jones (Duke University Medical Center, Durham, NC), explain that the risk of cardiovascular disease in women who have received treatment for breast cancer is increased in many different ways. "Cardiovascular clinicians need to understand this risk, and diagnostic, preventive, and/or therapeutic strategies that effectively address this need are urgently required," they say.
Jones et al note that breast cancer is the most common malignancy in American women, with approximately 213 000 new cases diagnosed in 2006. Although the incidence of breast cancer has increased by 0.2% per year between 1997 and 2000, improvements in detection and therapy have resulted in significant survival gains, with breast cancer-specific mortality decreasing almost 24% between 1990 and 2000. As a result, approximately 2.3 million American women are now living with a previous history of breast cancer, with sufficient survival to be at risk for cardiovascular disease.
The authors report that many of the chemotherapeutic agents used in breast-cancer management are associated with acute and long-term cardiac complications. Anthracycline-containing regimens are well recognized to trigger dose-dependent, cumulative, progressive cardiac dysfunction, manifested as decreased left ventricular ejection fraction (LVEF) and, ultimately, symptomatic congestive heart failure; radiotherapy also causes adverse cardiac events.
They point out that while endocrine therapy has not been clearly associated with cardiovascular injury, the new aromatase inhibitors have been associated with more cardiovascular events than tamoxifen, albeit a slightly lower incidence of thromboembolic events. Thus, longer-term follow-up is required to fully assess the associated cardiovascular risks.
In addition, the human epidermal growth factor receptor-2 (HER-2)-directed treatment of trastuzumab (Herceptin, Genentech) is associated with a heart-failure incidence of between 2.0% and 4.1% and asymptomatic cardiac dysfunction rates of between 3.0% and 18.0%; angiogenesis inhibitors are also known to be associated with cardiovascular complications, with reports of arterial thromboembolic events, increase in cardiac troponin, reductions in LVEF, and, most commonly, hypertension.
Jones et al also note that unfavorable lifestyle changes also come into the equation. "Physical activity and body weight are 2 major independent risk factors for cardiovascular disease that are often neglected when evaluating cardiovascular consequences of breast cancer therapy. It has been reported that, on average, early breast cancer patients decreased their physical activity by two hours per week from before to after diagnosis. Furthermore, more than 70% of breast-cancer patients gain between 2.5 to 6.2 kg of body weight during treatment," they write.
And to complicate matters still further, Jones et al explain that the presence of preexisting cardiovascular risk factors is itself a strong predictor for the development of breast-cancer-therapy-induced cardiovascular injury, making the likely lifetime risk for cardiovascular disease much greater. "Recent estimates suggest that physical inactivity confers a risk of breast cancer among white women of 2% to 15%, with overweight and obesity being associated with a 34% and 63% increased breast-cancer risk, respectively. It could be speculated, therefore, that physical inactivity and obesity rates may be even greater among early breast-cancer patients that, in turn, may translate into greater cardiovascular disease risk independent of the effects of adjuvant therapy."
Multiple-hit hypothesis
The authors refer to all these different causes of increased cardiovascular risk in breast-cancer survivors as the "multiple-hit" hypothesis. "We speculate that the consequences of the 'multiple hit' will become an increasingly important issue in the management of women with early breast cancer. Overall, this information is of critical importance to cardiovascular physicians, who will increasingly be called upon to evaluate and treat these women," they write.
Jones et al say that although the current and future consequences of the "multiple-hit" hypothesis will be clinically devastating, it is currently not possible to predict which patients are at increased risk of late-occurring cardiovascular disease. As current monitoring techniques (eg, echocardiography, radionuclide angiography) have limited ability to detect early cardiac damage, newer, more sensitive imaging modalities (single-photon-emission computed tomography, magnetic resonance imaging (MRI), exercise or dobutamine stress testing) as well as novel biochemical markers (brain natriuretic peptide, troponin I) that allow more accurate detection and quantification of subclinical cardiac damage are being explored, they add.
They recommend that a formal baseline cardiovascular risk assessment, using either Framingham or Reynolds risk scores, be performed before adjuvant therapy for breast cancer. "All women should be counseled about the value of a healthy lifestyle, and a program of individualized primary prevention should be undertaken as described in the American Heart Association guidelines. Unfavorable risk factors should be managed, ideally before the initiation of adjuvant therapy. Consideration should be given to more aggressive management of risk factors than might otherwise be indicated, in view of the 'multiple-hit' hypothesis presented here, although further research would be required before making such a recommendation universal," they conclude.
Source
Jones LW, Haykowsky M, Swartz JJ, et al. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007;50:1435-1441. Published online October 3, 2007.
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Clinical Context
Breast cancer is the most common malignancy in US women, with 213,000 new cases diagnosed in 2006 and incidence increasing by 0.2% per year, but mortality from breast cancer has fallen 24% between 1990 and 2000 with increasing numbers of survivors. Women living with breast cancer may be at increased risk for cardiovascular disease because of the risks associated with chemotherapy, hormonal therapy, and radiation as well as underlying cardiovascular risks.
This is a review of current therapies for breast cancer treatment and cardiovascular risk factors in women, to examine strategies for reducing the risk for cardiovascular disease among survivors of breast cancer.
Study Highlights
According to the Framingham data, women have a 39% lifetime risk for cardiovascular disease at age 50 years, with 40% having at least 1 preexisting risk factor and 17% with 2 or more risk factors.
Diabetes confers a risk for cardiovascular disease in 57% in women aged 50 to 75 years.
Risk factors for breast cancer include physical inactivity with a population-attributable risk for 2% to 15%, with overweight and obesity contributing a 34% to 63% increase in risk.
62% of patients with breast cancer are overweight or obese, and 36% are sedentary, similar to the general US female population.
Cardiovascular effects may be seen with polychemotherapy, radiotherapy, endocrine therapy, HER-2-directed therapies, and angiogenesis inhibition.
A formal baseline cardiovascular disease risk assessment before treatment for breast cancer with either Framingham or Reynolds risk scores is recommended.
Both acute and long-term cardiovascular effects are seen with anthracycline-containing regimens (doxorubicin, epirubicin), manifested as cumulative, progressive cardiac dysfunction with decreased LVEF leading to congestive heart failure.
Adjuvant trials have demonstrated left ventricular dysfunction in 10% to 50% of those receiving anthracycline-based therapies, which make patients more susceptible to long-term cardiovascular events.
Radiation has been associated for 18 years with 63 excess cases per 10,000 patient-years of cardiovascular events vs no radiation.
Radiation to either the left or right side of the chest is associated with increased risk for cardiovascular disease, lung fibrosis, and pulmonary disorders, but modern techniques provide lower risks for cardiovascular disease.
15-year cardiovascular mortality has been reported as higher for left-sided vs right-sided tumors (13% vs 10%).
Traditional endocrine therapy (tamoxifen, oophorectomy) is associated with an increased risk for venous thromboembolism and use of aromatase inhibitors with higher cardiovascular events.
HER-2-directed therapies are associated with incidence of heart failure of 2% to 4% and incidence of asymptomatic cardiac dysfunction of 3% to 18%.
Angiogenesis inhibitors (bevacizumab, sorafenib, sunitinib) and newer vascular-disrupting agents (ZD6126, TZT-1027) are reported to be associated with arterial thromboembolism.
Patients with breast cancer tend to decrease physical activity by 2 hours per week from before to after diagnosis.
More than 70% of patients with breast cancer gain 2.5 to 6.2 kg of weight during adjuvant therapy.
The multiple-hit hypothesis suggests that treatment regimens used for breast cancer increase the underlying cardiovascular risks and increase cardiovascular mortality.
It is not currently known whether treatment of risk factors modifies incidence of cardiovascular disease among women with breast cancer.
The study authors recommended that the American Heart Association guidelines for healthy lifestyle be adopted to prevent cardiovascular disease and preserve left ventricular function.
Initial treatment of hypertension should include optimal lifestyle behaviors, beta-blockers, and angiotensin-converting enzyme inhibitors with thiazides using step care.
Statins are recommended for hyperlipidemia and sulfonylurea and biguanides for type 2 diabetes.
Some agents may also have antitumor activity.
Exercise training has been shown to improve exercise capacity in survivors of breast cancer and reduced all-cause mortality.
More aggressive management of the risk for cardiovascular disease is recommended in survivors of breast cancer based on the multiple-hit hypothesis.
Pearls for Practice
Breast cancer chemotherapy and radiation are associated with the increased risk for left ventricular dysfunction, heart failure, and cardiovascular mortality.
Aggressive management following American Heart Association guidelines is recommended for survivors of breast cancer.