Addressing Cardiotoxicity in Breast Cancer Requires Multifaceted Approach

Clinicians with patients who are experiencing cardiotoxicity as a result of their breast cancer treatment should address the cardiotoxicity using a team-oriented approach based on guideline-directed therapies, according Jean-Bernard Durand, MD, MD, FACP, FCCP, FACC, FHFSA, who delivered a presentation on the topic during the 39th Annual Miami Breast Cancer Conference®.¹

“The predominant cardiotoxic medications in breast cancer are anthracycline-based therapies, tyrosine kinase inhibitors, trastuzumab [Herceptin], and pembrolizumab [Keytruda],” said Durand, who is a professor in the Department of Cardiology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston. “The goals of treatment, from a cardiology perspective, are very simple: keep our patients alive, keep them feeling well, and keep them out of the hospital.”

An absolute 10-point decrease in left ventricle ejection fraction (LVEF)is a common measurement of cardiotoxicity. Durand outlined the current guideline-directed treatment paradigm for patients who are admitted with heart failure. The agents include treatment with targeting the renin-angiotensin-aldosterone system upon admission, followed by β blockers,mineralocorticoids, and sodium-glucose cotransporter 2 inhibitors (SGLT-2s).

Durand contended that antidiabetic agents, such as SGLT-2s, can be very useful in treating cardiomyopathy and data show that they are equipped to play a much greater role for the treatment of cardiotoxicity. This is partially because there are similar pathophysiological features between diabetes and heart failure, the mechanistic effects of SGLT-2s, such as dapagliflozin (Farxiga) occurring in patients with and without diabetes, and the cardiovascular benefits of these agents being independent of glucose levels, Durand explained.

“I can promise you as oncologists, [over] the next 2 years, you are going to be overwhelmed by the data on antidiabetic drugs and the beneficial effects they have [for] cardiotoxicity and heart failure,” Durand said. “This is both [in terms of] preserving [ejection fraction] EF and a drop in EF.”

For patients with breast cancer, treatment guidelines for the most used agents, are in place for clinicians to monitor and address these adverse effects (AEs). For example, prior to the administration of trastuzumab, patients should undergo an evaluation for cardiac risk. If a patient is at risk of cardiotoxicity, the treating clinician should refer the patient to a cardio-oncologist. Following the initiation of treatment, the patient should be monitored for LVEF decreases every 3 months. Should a patient experience a decrease in LVEF of 10 or more points, they should be referred to a cardio-oncologist to begin either cardioprotective regimens which may or may not require treatment with trastuzumab. to stop.²

Immunotherapy-Related Cardiac Effects

Durand noted that immune-checkpoint inhibitors rarely have cardiac-related AEs, but those that do occur can be life threatening. For example, myocarditis is reported in less than 1% of patients treated with immune-checkpoint inhibitors; however, the AE is associated with a mortality rate of up to 50%.^3,4 Unfortunately, serious AEs, such as myocarditis are unpredictable, Durand said adding that early detection depends on recognizing nonspecific symptoms and close monitoring.

Durand noted that in MD Anderson’s Cardiology Department, patients with suspected myocarditis undergo a diagnostic workup consisting of laboratory, imaging, and procedures.¹ After a biopsy, a pathologist should evaluate a variety of laboratory values including troponin T, N-terminal pro b-type natriuretic peptide, and creatine kinase, among others. The imaging workup comprises a 12-lead electrocardiogram, a single-view chest X-ray, a 2-dimensional/3-dimensional complete echocardiogram, and a cardiac MRI delayed 48 hours after symptom presentation. The procedural workup consists of a right and left heart catheterization with an endomyocardial biopsy.

When patients present with noncardiovascular immune-related AE, clinicians should first check for troponin T, Durdan said. If levels are less than 100, no further workup for myocarditis is needed if the patient does not have any clinical symptoms. If troponin T levels are 100 or greater, clinicians should proceed to using the diagnostic and treatment algorithm for suspected myocarditis.

“If you are in the community, remember to develop a team [for patient care],” Durand said. “Those teams are going to include an oncologist, cardiologists, possibly a rheumatologist, and a pathologist.”

The treatment algorithm suggested by MD Anderson for a patient with clinically suspected myocarditis begins with stopping checkpoint inhibitor treatment and initiating treatment with steroids and plasmapheresis while waiting for the diagnostic workup. The suggested steroid treatment regimen is 1000 mg of methylprednisolone given intravenously daily for 3 days, then 1 mg/kg per day of prednisone for 7 days, decreasing to 0.5 mg/kg per day for 7 days, 0.33 mg/kg per day for 7 days, then to 10 mg per day for 7 days, and to finally 5 mg per day for 7 days. Plasmapheresis consists of 5 sessions preceded by endomyocardial biopsy.¹

When the diagnostic workup is returned after 3 to 5 days and is positive, rituximab (Rituxan) infusion should be administered at 2, 4, and 6 weeks. After rituximab infusion, if the patient had a LVEF greater than 50%, they should be treated with infliximab-axxq (Avsola) infusion at 2, 4, and 6 weeks. If LVEF is lower than 50%, mycophenolate mofetil 500 mg twice daily for 3 months. After either of these treatment cycles is completed, clinicians should continue monitoring troponin T for a response, daily for inpatient treatment and weekly for outpatient treatment.

References

1. Durdan JB. Cardiotoxicity in 2022: algorithms and treatment options. Presented at: 39th Annual Miami Breast Cancer Conference®. March 3-6, 2022; Miami Beach, FL.
2. Jafari L, Akhter N. Heart failure prevention and monitoring strategies in HER2-positive breast cancer: a narrative review. Breast Cancer Res Treat. 2021;186(2):295-303. doi:10.1007/s10549-021-06096-9
3. Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749-1755. doi:10.1056/NEJMoa1609214
4. Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721-1728. doi:10.1001/jamaoncol.2018.3923