Breast cancer treatment-induced cardiotoxicity

ABSTRACT

Introduction: Breast cancer is the most frequent cancer affecting women worldwide. In every setting, the majority of women are treated with an evergrowing arsenal of therapeutic agents that have greatly improved their outcomes. However, these therapies can also be associated with significant adverse events.

Areas covered: This review aims to thoroughly describe the current state of the evidence regarding the potential cardiotoxicity of agents commonly used in the treatment of breast cancer. These include chemotherapeutic agents, anti-HER2 therapies and CDK4/6 and mTOR inhibitors. Furthermore, issues related to the risk stratification and monitoring tools are explored.

Expert opinion: Anthracycline- and trastuzumab-related cardiac toxicities have been extensively studied. Substantial evidence is now available concerning additional anti-HER2 agents such as pertuzumab, T-DM1 and tyrosine kinase inhibitors; overall, the cardiotoxicity profile is reassuring. Cardiac events due to endocrine therapy are mostly ischemic and, in the context of prolonged therapy, need specific attention. Novel agents implicated in the treatment of hormone receptor-positive disease are potentially arrhythmogenic and the exact risk will need to be further refined. As for today, assessment of baseline risk factors prior to treatment initiation and cardiac imaging before and during treatment remains the optimal way to prevent cardiac dysfunction. Cardioprotective therapy in primary prevention is still a matter of debate.

KEYWORDS:

• Anti-HER2 agents
• breast cancer
• cardiac biomarkers
• cardiotoxicity
• cardiac imaging
• cardiac risk assessment
• chemotherapy
• endocrine therapy
• CDK4/6 inhibitors

Article highlights

• Anthracycline-induced cardiotoxicity is a very well-studied clinical entity and can cause direct apoptosis of the myocyte; their acute arrhythmogenic potential is less well-known

• Globally, the cardiotoxicity profile of pertuzumab, T-DM1, and the anti-HER2 TKIs (lapatinib, neratinib and afatinib) is favorable with no apparent major added toxicity as compared to the administration of trastuzumab alone.

• Endocrine therapy-related ischemic risks need to be taken into consideration especially in the context of the recent evidences of the potential added value of extended endocrine blockade up to 10 years.

• Novel approved targeted agents used in the treatment of hormone receptor-positive BC such as the CDK4/6 inhibitors palbociclib and ribociclib have been linked to QTc prolongation; special attention to this side effect in the coming trials is important.

• In addition to standard clinical risk evaluation, baseline and follow-up cardiac function imaging and cardiac biomarkers, genomic testing may represent a future mean by which identification of patients at high cardiac toxicity risk may be further refined.

This box summarizes key points contained in the article.

Declaration of interest

E Azambuja received honoraria from Roche and travel grants from Roche and GlaxoSmithKline outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper has not been funded.