There are more than 3.8 million women survivors of breast cancer now living in the U.S., and that number is growing rapidly. But while improvements in treatments are extending the lives of breast cancer patients, survivors are facing new risks from heart disease.
A new study clarifies which common therapies for breast cancer increase a patients risk cardiovascular disease and death. The Pathways Heart Study included 13,642 women with breast cancer and 68,202 women without breast cancer who were followed up to 14 years.1 Key findings from the study:
- Women who received anthracyclines and/or Herceptin (trastuzumab) had high risk of heart failure or cardiomyopathy, compared to women without a history of breast cancer. The highest risk was seen in women receiving both drugs.
- High risk of heart failure or cardiomyopathy was also seen in women who had received radiation therapy and aromatase inhibitor therapy, relative to women without a history of breast cancer.
- Women undergoing breast cancer treatments had elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease (blood clots in deep veins), cardiovascular disease-related death, and death from any cause compared to women without a history of breast cancer.
Patients may benefit from a treatment approach designed to reduce heart complications that weighs the benefits of specific therapies against potential damage to the heart, according to a scientific statement from the American Heart Association published in its journal Circulation.
Breast cancer survivors, especially older women over the age of 65, are more likely to die from cardiovascular disease than breast cancer, underscoring the importance of effectively managing heart disease risk factors during and following cancer treatment.
“Any patient who is going to undergo breast cancer treatment, whether they have heart disease at the beginning or not, should be aware of the potential effects of the treatments on their heart,” said Laxmi Mehta, M.D., chair of the writing group for the new scientific statement. “This should not deter or scare patients from undergoing breast cancer treatment, but should allow them to make informed decisions with their doctor on the best cancer treatment for them.
For example, some cancer treatments, such as HER-2 targeted therapies, can cause weakening of the heart muscle, a condition known as heart failure. HER-2 is a specific type of breast cancer. In some cases, the reduction in heart function is temporary and cessation of the treatment and/or the addition of heart medicines can improve function. But in some breast cancer patients, heart failure can be permanent. Because of this, the early development of heart failure can signal a need to slow down and/or alter a patient’s breast cancer treatment because of the risk for worsening the condition or the development of permanent heart failure.
Anthracycline - Doxorubicin
The most well-known cause of cardiac toxicity is the chemotherapy drug doxorubicin (Adriamycin®). Doxorubicin is a type of chemotherapy drug called an anthracycline. Anthracyclines are commonly used to treat breast cancer. Other anthracyclines are:
- Daunorubicin (Cerubidine®)
- Epirubicin (Ellence®)
- Idarubicin (Idamycin®)
Anthracycline associated damage to the heart may result in reductions of treatment doses. The side effects to the heart caused by anthracyclines may become chronic and life-threatening complication. Patients who are treated with anthracyclines often have their heart monitored prior to and during treatment to ensure prompt intervention should these side effects occur.5
Some small studies suggest that administering common chemotherapy agents in new ways may reduce heart disease risks. Studies have shown that when doxorubicin is administered slowly, rather than all at once, patients may have a lower risk of heart failure.
In addition, a drug called dexrazoxane that could reduce cell damage has also been approved for patients with metastatic breast cancer who receive high doses of doxorubicin. More studies will need to be done to confirm whether the results of the smaller studies are seen in larger groups of patients.4
The chemotherapy agent Doxil® (doxorubicin HCL liposome injection) reduces side effects to the heart that may be caused by the commonly used chemotherapy agent doxorubicin (Adriamycin®).
Herceptin is a precision cancer medicines that targets HER2 on breast cancer cells and was initially approved by the U.S. Food and Drug Administration (FDA) for treatment of early-stage breast cancer (that is HER2-positive in 2006.
Herceptin has the potential to damage the heart muscle, which can increase the risk for heart failure. As a result patients should be closely monitored following treatment.
Other treatments, such as radiation, can affect the heart arteries and cause the development of coronary artery disease or blockages. Some breast cancer treatment agents, such as anthracyclines, can result in abnormal heart rhythms that in some patients are benign but in others can lead to life-threatening heart rhythms. And, some treatments — like antimetabolites — can cause spasm of the heart arteries, which can cause chest pain symptoms but could lead to heart attacks as well.
Heart disease and breast cancer share a number of risk factors, including advanced age, poor diet, family history, physical inactivity and tobacco use. The fact that these diseases share some risk factors suggests that there are lifestyle choices, primarily diet and exercise, that could help decrease the risks of developing both diseases. Healthcare providers should monitor a woman’s heart health before, during and after breast cancer treatment.
Adherence to a number of ideal heart health behaviors or factors from the American Heart is associated with a trend towards a lower incidence of breast cancer. Life’s Simple 7 includes being physically active, achieving and maintaining a healthy body weight, eating a healthy diet, avoiding tobacco, maintaining healthy levels of blood pressure, cholesterol and blood sugar.
“Fortunately, with the advances in breast cancer treatment, there has been a growing number of survivors. However, during and after the treatment of breast cancer, having optimal control of heart disease risk factors is important, because older breast cancer survivors are more likely to die of heart disease than breast cancer,” Dr. Mehta said. “And that’s why Life’s Simple 7 is important for all patients with and without breast cancer.”
Although there are an estimated 47.8 million women in the U.S. who are living with cardiovascular diseases and approximately 3 million breast cancer survivors, many people regard breast cancer as the primary threat to women’s health. It is important to recognize the overlap of heart disease and breast cancer as both entities impact survival.
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
Radiation Therapy to the Breast and Heart Disease
Exposure to ionizing radiation during radiation therapy for breast cancer may increase the risk of heart attack or heart disease later in life, according to the results of a study published in the New England Journal of Medicine.
Many women with breast cancer are treated with breast-conserving surgery (lumpectomy) followed by radiation therapy in order to reduce the risk of cancer recurrence. Radiation therapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation—and the risks of this exposure have been unclear.
Researchers conducted a population-based, case-control study of 2,168 women who underwent radiation therapy for breast cancer between 1958 and 2001 in Sweden and Denmark. The analysis indicated that 963 women had major coronary events such as heart attack, surgery to clear a blocked artery, or death from ischemic heart disease. These women were compared to the 1,205 women without major coronary events.
The results indicated that the risk for a major coronary event grew in direct proportion to the dose of radiation. A unit of radiation is known as a “gray”. For every gray, the risk of a major coronary event rose by 7.4 percentage points. The average dose that women in the study received was 4.9 gray, which translates to an increased risk of 36 percent for a heart event. The women with the highest exposure (an average of 15.8 gray) had a 116 percent increased risk of heart events, which is slightly more than double the normal risk. Women treated for a tumor in the left breast had a higher risk of heart problems because of proximity since the heart is located slightly to the left.
The risk of coronary events after radiation begins within a few years after exposure and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiation therapy than other women.
The researchers note that the increased risk associated with radiation should not necessarily be cause for alarm. To put it into context, a healthy 50-year-old woman has a 1.9 percent chance of developing ischemic heart disease by the age of 80. If that same women is exposed to three gray of radiation, her risk increases by 22 percent—putting it at 2.4 percent, which is still quite small. What’s more—average radiation exposure is lower today (between one and five gray).
The researchers concluded that ionizing radiation for breast cancer can increase the risk of ischemic heart disease. Women who are already at an increased risk of heart disease may want to discuss alternative radiation techniques with their doctors.
The radiation therapy regimens used to treat breast cancer in the 1970s and early 1980s increase the risk of death from heart disease and lung cancer.
Radiation therapy to the breast for early-stage breast cancer is a common treatment modality. Unfortunately, radiation therapy to the breast cancer may also expose the heart and lungs to radiation. When the heart and lungs are exposed, the amount of radiation they receive varies with the side of the body that is treated. Radiation therapy to the left breast results in more radiation exposure to the heart than radiation therapy to the right breast. In the lungs, radiation exposure is the greatest for the lung on the side of the body that is irradiated.
To assess the effect of radiation therapy for breast cancer on subsequent heart disease and lung cancer risk, the researchers evaluated 308,861 women with early breast cancer diagnosed between 1973 and 2001. These women were identified from the U.S. Surveillance Epidemiology and End Results (SEER) cancer registries. The researchers evaluated whether women who received radiation for a left-sided breast cancer were more likely to die of heart disease, and whether lung cancer occurred more commonly on the side of the body that had been irradiated. Women with cancer in both breasts were excluded.
Among women diagnosed with breast cancer between 1973 and 1982, those who received radiation to the left breast were more likely to die of heart disease than women who received radiation to the right breast. After 10 to 14 years of follow-up, women who received radiation to the left breast were 42 percent more likely to die of heart disease than women who received radiation to the right breast; after 15 years of follow-up, they were 58 percent more likely to die of heart disease. There was no evidence of an association between the side of the breast cancer (left or right) and heart disease mortality among women who received radiation during later years (1983-2001), but there is less follow-up available for these women.
Radiation therapy for breast cancer between 1973 and 1982 also appeared to increase the risk of dying from lung cancer. Among women who received radiation and also developed lung cancer, the lung cancer most often developed on the side of the body that had been irradiated. This effect was especially apparent after 15 years of follow-up. There was no evidence of an association between lung cancer and radiation among women diagnosed with breast cancer between 1983 and 2001.
The researchers conclude that the radiation therapy regimens used for breast cancer in the 1970s and early 1980s increase a woman’s long-term risk of death from heart disease and lung cancer. Women who received radiation therapy for breast cancer during these years may wish to talk with their doctor about their heart and lung health. More recent radiation therapy regimens for breast cancer are likely to have much less of an effect on the heart and lungs.3
Is a woman who has had breast cancer more likely to die of breast cancer or of a cardiovascular disease, such as heart failure, heart attack or others?
Cardiovascular diseases, such as heart failure, heart attacks and strokes remain the leading cause of death in women, yet many believe breast cancer to be more deadly. Early detection and current treatments for breast cancer means there are increasing numbers of long-term breast cancer survivors, but these survivors also have a greater risk of cardiovascular diseases, in part resulting from the therapies used to treat the cancer.
In the United States, 47.8 million women are afflicted by cardiovascular disease, compared to 3.32 million women who are afflicted by breast cancer.
If some of the chemotherapy drugs and/or radiation treatments cause heart disease, what can be done to reduce the risk of heart disease?
The most common type of heart problem associated with breast cancer therapies is heart failure, where the heart muscle is weakened and cannot pump blood as effectively. While there are no proven treatments to prevent heart failure or other cardiovascular diseases in breast cancer patients, there are several promising treatments that have been explored in small studies.
Healthcare providers should monitor a woman’s heart before, during and after breast cancer treatment. The type of monitoring or surveillance depends on the type of breast cancer treatment being used. Using medications commonly used to treat heart failure, such as beta blockers, are recommended if the heart muscle weakens. Some studies also suggest that administering common chemotherapy agents using different methods, may reduce the related risks to heart disease. For example, when the chemotherapy agent doxorubicin is administered over a longer period of time, rather than at a faster rate, patients may have a lower risk of heart failure.
Before any of these treatments can be recommended, more large-scale studies will need to be done to confirm whether the results of the smaller studies are valid.
Do breast cancer and heart disease share many of the same risk factors?
Yes – older age, onset of menopause, low-quality diets, family history, hormone replacement therapy, obesity, lack of sufficient physical activity, alcohol and tobacco use increase the risk of both breast cancer and diseases of the heart and blood vessels.
While there is nothing you can do about your age or family history, following Life’s Simple 7 — seven steps people can take to reduce the risk of heart disease – may also help reduce the risk of breast cancer.
- Darby SC, Ewertz M, McGale P, et al. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. New England Journal of Medicine. 2013; 368: 987-998.
- Darby SC, McGale P, Taylor CW et al. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncology. 2005;6:557-65
- Marty M, Espie M, Llombart A, et al. Multicenter Randomized Phase III Study of the Cardioprotective Effect of Dexrazoxane (Cardioxane®) in Advanced/Metastatic Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy. Annals of Oncology. 2006; 17: 614-622.
O’Brien MER, Wigler N, Inbar M, et al. Reduced Cardiotoxicity and Comparable Efficacy in a Phase III Trial of Pegylated Liposomal Doxorubicin HLC: CAELYX/Doxil®) Versus Conventional Doxorubicin for First-Line Treatment of Metastatic Breast Cancer.
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