Heart disease and breast cancer

Dr YT Singh explains that heart disease is the reason why breast cancer patients due to receive cardiotoxic therapy need a cardiovascular assessment before, during and after cancer treatment..

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Breast cancer is the most common malignancy in women. There is a one-in-eight chance of women being diagnosed with invasive breast cancer. Happily, due to excellent chemotherapy, radiotherapy and surgery, breast cancer patients are being cured in 90% of cases. However, breast cancer is not the main cause of death in women, cardiovascular disease (heart disease) is.

And to make it a double whammy, the drugs used to treat breast cancer just happen to be cardiotoxic in many instances; that is, they may cause heart problems.

So, breast cancer survivors are living longer and are not succumbing to the cancer. However, the concern is that breast cancer survivors may succumb to heart disease caused by the medium- and long-term complications of chemotherapy and radiotherapy.

Cardio-oncology

Stemming from the understanding of the need to treat cancer patients holistically in respect of the cancer and heart disease, a new medical speciality has been created, that of cardio-oncology.

A cardio-oncologist is a cardiologist who has an in-depth knowledge of the cardiovascular complications of cancer therapy and applies international cardio-oncology guidelines for the timeous detection and treatment of cardiovascular complications in the cancer patient.   

It follows that the cardio-oncologist needs to be involved in the management of the cancer patient before, during and after cancer therapy, to ensure the cancer patient doesn’t develop cancer therapy-related cardiac dysfunction (CTRCD).

The cardio-oncologist needs to work closely with the oncologist to make sure that the cancer patient not only obtains a successful cancer outcome, but doesn’t succumb to a cardiovascular event.

In many countries, cardio-oncology units exist side-by-side with oncology units. This is the case in US, UK, Israel, Canada, Poland, Spain and Brazil, amongst others.

COSOSA

In South Africa, the Cardio-Oncology Society of Southern Africa (COSOSA) has been formed, with Dr YT Singh (cardiologist) as president, Dr Ines Buccimazza (breast and endocrine surgeon), Dr Ria David (medical oncologist), Prof Andrew Sarkin (cardiologist), Dr Jenny Edge (breast and endocrine surgeon), Dr Len Steingo (cardiologist), Dr Owen Nosworthy (medical oncologist), Prof Alecia Sherriff (radiation oncologist) and Prof Alan Davidson (paediatric haematologist) on the board. 

The organisation is affiliated to the International Cardio-Oncology Society (ICOS), based in USA.

Anthracyclines

Anthracyclines comprise one of the most useful classes of drugs for treatment of breast cancer, but are known to cause cardiomyopathy (cardiac muscle dysfunction) or heart failure in 10% of patients at conventional dosages. The incidence of cardiac dysfunction increases with higher dosages. 

Anthracyclines also cause heart rhythm problems.

Most cardiac dysfunction usually occurs in the first year after therapy but can occur up to 10 years later. 

The risk of cardiotoxicity is increased when these drugs are used in combination with trastuzumab, radiation, and in older age patients (over 60), and in patients with risk factors, such as high blood pressure, diabetes, obesity, high cholesterol and smoking.  

If not diagnosed and treated timeously, anthracycline-induced heart muscle dysfunction can be irreversible. The good news is it may be treatable, if detected early.

Trastuzumab

Trastuzumab has resulted in significant cancer survival and reduced breast cancer recurrence.

Unfortunately, it may result in cardiotoxicity and heart failure, especially when combined with anthracyclines. Cardiotoxicity may also occur when trastuzumab is used with chest radiation, and when the patient has cardiac risk factors already mentioned. 

Trastuzumab cardiotoxicity is often reversible either by withholding therapy or commencing heart failure therapy as early as possible, i.e. when cardiac dysfunction is detected, even when the patient has no symptoms.

Radiotherapy

Radiation to the chest, where the heart is in the treatment field, may cause cardiac problems involving heart muscle, coronary arteries, pericardium, heart valves, and the conduction system.

Cardiovascular effects can occur as early as five years after radiation exposure in breast cancer survivors, and the risk remains for up to 30 years. Late heart failure is a complication. However, it can be treated successfully if diagnosed early, and regular cardiac monitoring after radiation is vital, at least every five years.

Other chemotherapies

Other classes of chemotherapy used in breast cancer and the cardiovascular problems they may cause are:

CHEMOTHERAPY	CARDIOVASCULAR PROBLEMS
Alkylating agents (cisplatin, cyclophosphamide)	Heart failure, arterial thrombosis, arrhythmias.
Taxanes (paclitaxel)	Heart block, arrhythmias.
Antimetabolites (5-flurouracil, capecitabine)	Coronary thrombosis, arrhythmias.
Endocrine therapy (tamoxifen, anastrozole)	Venous thrombosis, thromboembolism, arrhythmias, heart failure, atherosclerosis.
Ribociclib	Heart conduction problems.

Cardio-oncology assessment

Newer modalities of screening for cardiotoxicity are:

1. 3D echocardiography: Measuring ejection fraction for cardiac function (now recommended by international cardio-oncology societies). Please note, 2D echocardiogram performed, by unsupervised technologists, for ejection fraction, as the sole cardiac assessment, is not ideal, especially now, with our better understanding of cardiac problems facing cancer patients on cardiotoxic therapy. Echocardiography is an extension of the clinical assessment and should not be done in isolation.
2. Echo Strain Imaging and Speckle Tracking: For early detection of cardiac muscle dysfunction. Global Longitudinal Strain (GLS) is an early indicator of heart muscle dysfunction, long before the ejection fraction starts to decline. By the time the ejection fraction drops, it may be too late to allow for heart muscle recovery or reversibility.
3. Cardiac MRI: Accurately detects cardiac dysfunction and assesses other cardiac structures. Drawbacks are expense, availability of equipment, and lack of expertise to interpret.
4. Multigated acquisition (MUGA): Only useful for measuring ejection fraction. Again, expense, availability, excess radiation exposure, and inability to assess other cardiac structures are drawbacks. 
5. Cardiac Biomarkers: Early elevation of troponins (proteins found in heart muscle fibres), especially when combined with GLS, can predict cardiac dysfunction, long before the ejection fraction declines. NT-pro BNP (natriuretic peptide) is also useful to assist in diagnosis of heart failure.
6. CT Coronary Angiography: Useful non-invasive method of assessing coronary artery narrowings in cancer patients with chest pain.

Header image by Freepik