How Does Cardiotoxicity Present Itself in Patients With Cancer?

A trio of abstracts presented at this year’s annual meeting of the American Society of Clinical Oncology focused on cardiotoxic effects of cancer treatment and how cardiac disease remains a barrier to effective cancer therapy among patients with cancer and survivors.

“There's a 3-pronged approach in cardio-oncology. We describe short-term and delayed cardiotoxic effects of cancer treatments. We explain strategies for screening and monitoring of cancer patients for cardiovascular toxicity before, during, and after cancer treatment. And lastly, we would like to outline a multidisciplinary approach between cardiologists and oncologists to manage cardio-oncology patients using recommendations and optimizing survivorship outcomes,” noted Roohi Ismail-Khan, MD, MSc, medical oncologist and co-director of the cardio-oncology program H. Lee Moffitt Cancer Center.

Five-year survival rates noticeably improved across a variety of cancers between 1971 and 2011, Khan pointed out. Among the cancer with the most significant improvements are prostate, non-Hodgkin lymphoma, and leukemia. However, these longer survival times mean that late-term adverse effects are becoming more common, such as cardiovascular disease (CVD), especially among patients with early-stage breast cancer who are beginning to die more from CVD than the cancer itself.

Cardiotoxicity

The first 2 abstracts that Ismail-Khan presented¹ focused on results from the Pathways Heart Study,^2,3 from the National Cancer Institute and Kaiser Permanente Northern California (KPNC), which is examining CVD and its risk factors among women with breast cancer, women with no history of the disease, and survivors. Patient data came from KPNC electronic health records for all cases of invasive breast cancer diagnosed from 2005 to 2013.

CVD was classified as major (eg, ischemic heart disease, heart failure, cardiomyopathy, stroke) or other (eg, arrhythmia, cardiac arrest, valvular disease, etc). in addition to statistical analyses, subgroup analyses looked at differences among patients who received chemotherapy, radiation, and hormonal therapy.

There were 14,942 women in the breast cancer cohort and 74,702 in the control group (no breast cancer), with an average age of 62 years and an average body mass index of 28.3 kg/m² at diagnosis. The average follow-up was 7 years.

The overall results show an increased the risk of both hypertension and diabetes:

• Hypertension: HR, 1.18 (95% CI, 1.13-1.24)
• Diabetes: HR, 1.25 (95% CI, 1.18-1.33)

Treatment for breast cancer with chemotherapy, left-sided radiation therapy, and endocrine therapy was also shown to increase the risk of cardiotoxic effects. In particular, chemotherapy increased the risk of heart failure and cardiomyopathy.

Ismail-Khan noted, however, that other factors influence these outcomes in patients with cancer, and these include genetics, cancer type, and lifestyle factors.

Exercise

The third abstract⁴ Ismail-Khan presented focused on using exercise to improve heart health among patients with testicular, breast, and colon cancers as well as non-Hodgkin lymphoma (NHL) who have undergone treatment and were randomized to a 24-week exercise intervention either during chemotherapy (n = 131) when it finished (n = 135). The primary outcome was effect on VO₂ peak, “the highest value of VO₂ attained upon an incremental of other high-intensity exercise test, designed to bring the subject to the limit of tolerance.”¹

The average age of the patients were 33 years for testicular cancer, 52 years for breast cancer, and 64 years for both colon cancer and NHL.

Although both groups benefitted, the results overwhelming showed that the early-exercise group fared better, with less of a decline in their VO² peak and quality of life. They also had less overall general (P = .002) and physical fatigue (P < .0001) at the first time point.

At the second time point, VO² peak (P = .9), quality of life (P = .7), general fatigue (P = .3), and physical fatigue (P = .7) were comparable between the exercise and nonintervention groups.

A supervised exercise program is best, Ismail-Khan noted, but “the earlier we introduce exercise in our chemotherapy adjuvant patients, the better.”

“These cardio-oncology studies are looking at modifying multiple areas,” she concluded, “so that we can have better outcomes for our cancer survivors. I tell my patients when I see them that, ‘While we are curing your cancer, we don’t want to increase your risk of dying from yet another disease. So, while we are curing your cancer, we have to concentrate on preventing heart disease at the same time.”

References

1. Ismail-Khan R. To the heart of the matter: understanding and improving cardiovascular health in cancer. Presented at: ASCO20 Virtual; May 29-31, 2020. Accessed May 29, 2020. https://meetinglibrary.asco.org/record/188934/video

2. Greenlee H. Risk of cardiovascular disease in women with and without a history of breast cancer: the Pathways Heart study. Presented at: ASCO20 Virtual; May 29-31, 2020. Accessed May 29, 2020. https://meetinglibrary.asco.org/record/188171/abstract

3. Kwan ML. Onset of cardiovascular disease risk factors in women with and without a history of breast cancer: the Pathways Heart study. Presented at: ASCO20 Virtual; May 29-31, 2020. Accessed May 29, 2020. https://meetinglibrary.asco.org/record/188346/abstract

4. van der School GGF. Effect of a tailored exercise intervention during or after chemotherapy on cardiovascular morbidity in cancer patients. Presented at: ASCO20 Virtual; May 29-31, 2020. Accessed May 29, 2020. https://meetinglibrary.asco.org/record/187836/abstract