The survival rate of women with breast cancer has been steadily increasing each year since 2007. The 5-year survival rate for women with nonmetastatic invasive breast cancer is currently 90%.1 As survival rates have increased, studies have demonstrated that rates of cardiovascular disease in the same population have been increasing as well. This is an important observation, as cardiovascular disease is already a common condition in women, and is currently the leading cause of death in women in the United States.2 

The recently published Pathways Heart Study sought to determine the risk of cardiovascular disease and death in women who underwent treatment for breast cancer compared with women who did not have breast cancer. The study looked at multiple treatments for breast cancer, including chemotherapy, radiation, and endocrine therapy. The chemotherapy groups were further broken down into 4 subset groups: anthracyclines without trastuzumab, anthracyclines with trastuzumab, trastuzumab without anthracyclines, and chemotherapy that did not include either trastuzumab or anthracyclines.3 

For those who underwent radiation therapy, both sides of the body were recorded, with special focus on those who received radiation to the left side. Endocrine therapy was grouped into treatment with tamoxifen or aromatase inhibitors.3 


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Cardiovascular Risks With Breast Cancer Treatments

Trastuzumab The cardiac risk factors associated with the HER2-directed therapy trastuzumab are well established. Trastuzumab has the potential to cause left ventricular (LV) dysfunction, hypertension, and arrhythmias, and requires routine cardiac evaluation during therapy. If LV dysfunction is documented, trastuzumab should be held and rechallenged based on improvement of LV function.4 

Anthracyclines Cardiotoxicity is a known risk with use of anthracyclines, and due to cumulative risk, lifetime dosages have been established. The exact cardiovascular risk is dependent upon the age of the patient as well as the cumulative dose of anthracyclines they received. Cardiotoxicity from anthracyclines primarily consists of cardiomyopathy resulting in heart failure. 

Radiation Radiotherapy for breast cancer has the potential to cause long-term cardiac toxicities, including coronary artery disease, myocardial infarction, heart failure, arrhythmias, and valvular disease.5 

Endocrine therapy Studies have demonstrated that the cardiovascular risks associated with endocrine therapy are most likely to occur with use of aromatase inhibitors over tamoxifen. Aromatase inhibitors have the potential of causing coronary artery disease, myocardial infarction, arrhythmias, heart failure, pericarditis, and valve disease. Tamoxifen has actually shown to be cardioprotective but does carry an increased risk of venous thromboembolism (VTE).6

The Pathways Heart Study 

The Pathways Heart Study is a large, prospective cohort study that enrolled 13,642 women with breast cancer and 68,202 matched participants without breast cancer (controls). The study findings did not associate radiation therapy, chemotherapy, or endocrine therapy with the development of ischemic heart disease. However, the findings did show the incidence of cardiovascular events and cardiovascular-related death was higher in women treated for breast cancer.3 

Interestingly, rates of cardiac arrest were more likely to happen in women whose treatment included left-sided radiation, any-sided radiation, or the use of aromatase inhibitors. The risk of cardiac arrest in women treated with chemotherapy or tamoxifen was not shown to be increased.3

Chemotherapy Women who received anthracyclines without trastuzumab, anthracyclines with trastuzumab, and trastuzumab without anthracyclines were found to have higher rates of cardiomyopathy and heart failure.3 

Interestingly, the highest rates of cardiomyopathy were observed in those who received anthracycline chemotherapy. Trastuzumab-associated cardiomyopathy was less likely. This is thought to be due to the cumulative incidence of irreversible toxicity with anthracycline vs the possibly reversible toxicity with trastuzumab. However, the risk of cardiomyopathy and heart failure was highest in women who received both an anthracycline and trastuzumab.3 

Arrhythmias were more likely to occur in women who received anthracycline chemotherapy. VTE was also higher in all chemotherapy groups compared with untreated women. The highest risk for VTE was in the group who received chemotherapy but not anthracycline or trastuzumab.3 

Radiation For women who had radiation to either side, risks were higher for heart failure, cardiomyopathy, cardiac arrest, VTE, and cardiovascular-related death. Women who received left-sided radiation were noted to have higher rates of heart failure, cardiomyopathy, cardiac arrest, valvular disease, and cardiovascular-related death.3 

Endocrine therapy Although VTE is associated with the use of tamoxifen, incidence wasn’t statistically significant compared with the untreated group. The aromatase inhibitors group had an increased risk of heart failure, cardiomyopathy, stroke, arrhythmia, cardiac arrest, and cardiac-related death.3 

Conclusions

The results of this study help shed light on the cardiovascular risks for women who have been treated for breast cancer, highlighting the significant risks these women face. 

This study also highlights the need for further research on how combinations or sequencing of therapy adjusts the risk of cardiovascular disease. Although the results were adjusted for combination therapy, how possible adjustments in timing or sequencing could reduce risks was not demonstrated.3 

The cardiovascular risks associated with breast cancer treatment are not insignificant, and this population is already at risk for cardiovascular disease. Further research is needed to help determine the best way to mitigate the risk of cardiovascular disease from breast cancer therapy. 

Future research can evaluate not only preventing cardiovascular disease but also make suggestions for surveillance and treatment of cardiovascular complications. More frequent treatment monitoring, weight management strategies, and tighter control of hypertension are some suggestions for future evaluation.7 

References

  1. American Society of Clinical Oncology. Breast cancer: statistics. Cancer.net. Published January 2022. https://www.cancer.net/cancer-types/breast-cancer/statistics
  2. Centers for Disease Control and Prevention. Women and heart disease. CDC website. Last reviewed July 12, 2022. https://www.cdc.gov/heartdisease/women.htm
  3. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: the Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi:10.1200/JCO.21.01736
  4. US National Library of Medicine. Label: Herceptin- trastuzumab injection, powder, lyophilized, for solution. Updated October 19, 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2&audience=consumer
  5. Cheng YJ, Nie XY, Ji CC, et al. Long‐term cardiovascular risk after radiotherapy in women with breast cancer. J Am Heart Assoc. 2017;6(5):e005633. doi:10.1161/JAHA.117.005633
  6. Matthews AA, Hinton SP, Stanway S, et al. Endocrine therapy use and cardiovascular risk in postmenopausal breast cancer survivors. Heart. 2021;107(16):1327-1335. doi:10.1136/heartjnl-2020-317510
  7. Kwan ML, Cheng RK, Iribarren C, et al. Risk of cardiometabolic risk factors in women with and without a history of breast cancer: the Pathways Heart Study. J Clin Oncol. 2022;40(15):1635-1646. doi:10.1200/JCO.21.01738

This article originally appeared on Oncology Nurse Advisor