Cardiological Impacts of Cancer Treatments

Cancer Treatments are Malicious to the Heart

 There are multiple types of cancer treatments such as radiation therapy, and chemotherapy, hormone therapy and immunotherapy; these treatments have been beneficial to treating tumors. Chemotherapy is a universal treatment that works throughout the body to kill the cancer cells or shrink the tumor. Radiation therapy kills cancer cells by destroying their DNA directly or “create charged particles within the cells that can in turn damage the DNA” (Bovelli et al). Ten years ago, breast cancer and colorectal cancer patients had a 50% chance of living five years after diagnosis, but today, 90% or more survive the five years or longer (Bovelli et al). Sixteen years ago, 60% of patients diagnosed with chronic myeloid leukemia-type of cancer that interferes with blood cell production- barely survived eight years; today, there is a 95% chance of patients living at least ten years (Soujeri et al). New anticancer therapies have led to longer life expectancy; conversely, treatment-related side effects have become an issue for cancer survivors. Cardiotoxicity is the most common side effect of anticancer therapies because of high mortalities. Some cardiovascular effect happens during treatments; other symptoms may present itself long after treatment. About 62% of breast cancer patients developed heart failure within 90 days (Aleman et al). Cancer treatments are beneficial in shrinking and destroying tumor cells, on the other hand they, cancer treatments may result in cardiotoxicity which leads to heart failure, congestive heart failure (a heart weakness that leads to a buildup of fluid in the lungs), myocardial ischemia (low blood flow to the heart), arrhythmias (abnormal heart beat), hypertension, thromboembolism (a clot causing an obstruction in a blood vessel) and pericarditis (inflammation in the heart).

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 The number of cancer patient survivors continues to increase because of both advances in early detection and treatment of cancerous cells. The 3 most prevalent cancers are prostate (3.3 million) colon and rectum (800 thousand), and melanoma (700 thousand) among males and breast (3.6 million), uterine corpus (800 thousand), and colon and rectum (700 thousand) among females (Minz). More than one-half, about 58%, of survivors were diagnosed within the past 15 years, and almost one-half, 46%, are aged 70 years or older (Aleman et al). There is a staging system that’s used to classify cancers. The staging system assesses cancer in 3 ways: the size of the tumor, where its located, and if it caused other tumors to grow. Once the classifications are determined, a stage of I, II, III or IV is given. Cancer treatments have progressed rapidly in the last few years. The overall 5-year survival rate in breast cancer patients has dramatically increased from 75.1% to 90.0% from 2001-2007(Bovelli et al). Also, the addition of bevacizumab, an anti-growth factor that inhibits tumor growth, to radiation therapy provided a significant benefit to patients with colorectal cancer (Moynihan). In a recent trial for pancreatic cancer, there positive findings from a “phase III of the trial which led to the regulation of nab-paclitaxel, a chemotherapy drug, as a treatment option for patient with metastatic pancreatic cancer, a pancreatic cancer that spreads” (Yusuf et al).

However, the antitumor treatments’ list of effects has shocked and dazed cardiologists and oncologists-cancer doctors-on how to come up with heart protection approaches. Two of the busiest study areas in medicine are consorting to help cancer patients survive treatment and prevent heart disease because cardiovascular disease (CV disease) is the “nation’s first principal killer, cancer is the second” (Aleman et al). The cardiovascular side of effects that arise from cancer therapy are terrifying. Some treatments cause the heart muscle to weaken, blood pressure to rise dramatically and may increase blood clots. Hormonal therapies which are a type of cancer treatments are the leading cause to stroke, heart attacks and ischemia- low blood flow to the heart. Gradually, cancer survivor patients were dropping with heart failure or worse, having unexpected heart attacks, some in there mid to late 20’s and early 30’s (Yusuf et al). Chemotherapy-induced cardiotoxicity is the most feared adverse effects and has been reported in up to 53% of patients up to thirty years late, the majority of which occurring after completion of therapy.

Moreover, the occurrence of cardiotoxicity depends on the type of drug administered to a patient and the amount of dosage. The higher the dosage, the more likely for the cancer survivor to develop cardiovascular disease. of the chemotherapy drugs associated with congestive heart failure are anthracyclines, trastuzumab and cyclophosphamide, and the radiation therapy drugs that are associated with ischemia and thromboembolism are antimetabolites, cisplatin and thalidomide. 5% of women who took trastuzumab for breast cancer had heart failure and were admitted to the heart transplant list. Anthracycline cardiotoxicity occurs chronic within days of treatments, within first year after treatment, 16%-21% survivors were found to have late onset chronic progressive, cardiomyopathy. There is a 10% frequency of cardiotoxicity among 2625 anthracycline-treated patients, more than half of the patients had arrhythmias, hypertension, thromboembolism or pericarditis occurrence within the first year after completing their treatment. Incidences of heart failure were 15%, 20%, and 38% with a cumulative dose of 400, 500, and 700 mg/m2 of anthracyclines.

Furthermore, radiation- related heart injury after radiation therapy are also common in cancer patients with Hodgkin’s lymphoma and early- stage breast cancer. Radiation- induced Cardiovascular toxicity is progressive and induces complex diseases like pericarditis, coronary artery disease, and diastolic dysfunction. In the article “Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease,” a Swedish study that included 55,000 patients, the mortality percentage for CV diseases were 95 %. Radiotherapy injury to multiple heart tissues and structures can cause radiation- induced CV diseases such as the heart muscles weaken causing the build- up of fluid in the lungs and in the surrounding tissue, it could also cause atherosclerosis (fatty deposits in the coronary arteries).

 Additionally, targeted drugs are compounds used in chemotherapy, acting through inhibition of targeted molecules, protein kinases, because of their role in cell signal transduction. Trastuzumab, aka Herceptin, is a humanized antibody that targets the growth factor receptor 2 in breast cancer by blocking it. The rate of trastuzumab-induced congestive heart failure is 45%-65%, it increases with ages of 50 years or older, it rises even higher when used with anthracycline plus cyclophosphamide (Aleman et al). Bevacizumab, another humanized monoclonal antibody against vascular endothelial growth factor receptor, can be associated with heart failure or arterial thromboembolic events or venous thromboembolism, and it can induce severe hypertension (Groarke and Nohria). The incidence of heart failure reported with cyclophosphamide therapy series from 7%-28%, and the risk of myocardial ischemia and thromboembolism is dose related; it occurs within couple of days after administration of the first cycle (Sonmez et al). Another most common drug used in chemotherapy and hormone therapy is fluorouracil. A cardiotoxic effect of fluorouracil is angina (chest pain), occur generally within 5 days after the first dose (Sonmez et al). Also, they can cause spasms of the coronary arteries and initiate a minor heart attack that could lead to an undetectable, large heart attack.

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 Researchers believe that some antitumor treatments such as immunotherapy and hormone therapy, are cause more cardiovascular diseases than chemotherapy and radiation therapy drugs. Indicative results reveal a large variety of cardiotoxic events with manifestations such as heart failure, cardiomyopathy (abnormal heart wall), and arrhythmias. According to the “Immunotherapy related Cardiomyopathy,” the risk is higher for the development of heart failure when the immunotherapy ipilimumab or Lapatinib, a kinase inhibitor targeting internal growth factor 2 receptor, which seems to have a low incidence of heart failure or other adverse cardiac effects, drugs are used than the single agent anthracycline which is used in chemotherapy (Sonmez et al). Between August 2015 and January 2017, 17.5% of patients who received ipilimumab cultivated shortness of breath because of heart failure (Groarke and Nohria). On the other hand, antitumor therapies such as chemotherapy and radiation therapy are more effective in causing cardiovascular diseases. As previously mentioned, “Chemotherapy-induced cardiotoxicity is the most common side effect; it has been reported in 60% of all cancer survivor patients during or after completion of course treatment” (Soujeri et al).

 In conclusion, antitumor treatments have many advantageous effects such as the shrinkage and annihilation of tumor cells, 90% or more survive the five years term giving patients more time, some patients live up to 70 years old (Moynihan). However, chemotherapy, radiation therapy etc. treatments causes cardiovascular diseases such as pericarditis, thromboembolism, coronary artery diseases congestive heart failure and arrhythmias. These side effects don’t always present itself at once, symptoms might rise 10-15 years after the course of treatment has been given. Also, it depends on the amount of dosage given, dosage between 400-700mg/m2 of anthracycline might increase the chances of heart failure than 400mg/m2 of trastuzumab. Oncologists and cardiologists are working on a developing a way of preventing cardiovascular disease while administrating cancer treatments to reduce the mortality rate.

Works Cited

• Aleman, Berthe M.P., et al. “Cardiovascular disease after cancer therapy.” EJC Supplements, Elsevier, 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4250533/.
• Bovelli, D., et al. “Cardiotoxicity of chemotherapeutic agents and radiotherapy-Related heart disease: ESMO Clinical Practice Guidelines | Annals of Oncology | Oxford Academic.” OXFORD Academic, Oxford University Press, 1 May 2010, academic.oup.com/annonc/article/21/suppl_5/v277/194029/Cardiotoxicity-of-chemotherapeutic-agents-and.
• Groarke, John D., and Anju Nohria. “Anthracycline Cardiotoxicity: A New Paradigm for an Old Classic.” Circulation, American Heart Association, Inc., 2 June 2015, circ.ahajournals.org/content/131/22/1946.
• Minz, Madhu Mary. “Managing Cancer Patients: The Heart Really Matters.” Feb. 2017, www.jcpconline.org/temp/JClinPrevCardiol6260-1695823_044238.pdf.
• Moynihan, Timothy J. “Chemotherapy side effects: A cause of heart disease?” Mayo Clinic, Mayo Foundation for Medical Education and Research, 13 Oct. 2015, www.mayoclinic.org/diseases-conditions/cancer/expert-answers/chemotherapy-side-effects/faq-20058319
• Sonmez, Ozlem, et al. “Immunotherapy Releated Cardiomyopathy.” Journal of Clinical Oncology, 2017, ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e14601.
• Soujeri, Bayan, et al. “23 Surveillance and Incidence of Chemotherapy-Induced Cardiotoxicity in Breast Cancer: A Long Term Observational Study.” Heart, BMJ Publishing Group Ltd and British Cardiovascular Society, 1 June 2016, heart.bmj.com/content/102/Suppl_6/A14.2.
• Yusuf, Syed Wamique, et al. “Radiation-Induced Heart Disease: A Clinical Update.”  Cardiology Research and Practice, SAGE-Hindawi Access to Research, 27 Feb. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3051159/.