Cardiac Disease After Breast Cancer Treatment: Make Sure to Check Our Blind Spot!

In this issue of the Journal of the National Cancer Institute, Dr Abdel-Qadir et al. report on a population-based retrospective study of a long-term analysis of the cardiovascular (CV) outcomes of patients with early breast cancer (EBC) who have undergone treatment in Ontario, Canada (1). These data are very carefully reviewed and synthesized. The treated patients are compared to a control group of age-matched patients on a 1:3 ratio allowing a robust comparison for CV risk factors and outcomes in these patients with breast cancer to an appropriate control population. These authors report on some very interesting findings, especially when compared to previous work in similar breast cancer groups. In short, the authors report that even among patients treated with potentially cardiotoxic therapy, such as anthracyclines or trastuzumab, the rate of admission for heart failure (HF) is surprisingly low, even after 10 years, especially when one considers that the most common cardiac issue encountered in these patients being treated for cancer is actually coronary artery disease or the development of ischemic heart disease (IHD). This report also deals with other common CV events such as stroke and arrhythmia, which thankfully occur at a low rate over 10 years but still occur more frequently than control patients during that time. It is expected that patients with EBC, especially those treated with anthracyclines and/or trastuzumab, would have a higher incidence of HF hospitalization compared to age-matched patients. Fortunately, the overall risk of HF related to chemotherapy or targeted therapy is much lower than that seen with other large database studies reported previously and portends an overall excellent CV prognosis despite cancer treatment (2,3).

Abdel-Qadir et al. should be congratulated on many fronts. The long period of follow-up of 10 years definitely allows a practitioner to understand the long view of cancer treatment as it relates to CV disease. There is extensive information about concomitant medications and CV risk factors, which allows one to see that this population does represent a “real-world” population and therefore reflects common practice. As it turns out, in this Canadian database, those who are treated for EBC are more likely to be on medications for CV risk factors, such as renin angiotensin inhibitors, beta-blockers, and statins, compared to the control patients. This fact may indicate that Canadian providers are more in tune to the concept of shared risk factors for CV disease and cancer (4). Furthermore, those patients with EBC who are being treated with cardiotoxic therapy were less likely to have preexisting CV disease, indicating that those providers are doing a risk assessment and potentially altering cancer treatment, even if informally, before initiating therapy.

The implications from this study include the idea that HF, as an admitting diagnosis in patients treated for EBC, may not have a very high rate of occurrence. This is certainly good news and far different than the rates reported from the SEER database studies a few years ago in the United States (2,3). There are differences to note between those studies and this one: The rate of HF defined in the SEER database was any diagnosis of HF over 5 years of follow-up, whereas this report is regarding those admitted to the hospital for HF in Canada. The reporting systems are surely not the same, and the rate of admission for HF would likely be much different than any International Classification of Diseases, Ninth Revision (ICD-9) code for HF in any setting, including outpatient coding such as with the SEER database. It is striking that the rate of HF in those previous studies were in the range of 20% at 5 years of elderly breast cancer patients who were treated with both anthracycline and trastuzumab (2,3), whereas in this study, the range for those admitted for HF after 8 years was only 1.5%. This is a major incidence gap, and the most positive interpretation of these findings would be that the providers in Canada may be much more likely to address common risk factors and effectively stratify patients for cardiotoxic therapy in a more discerning manner than in the United States. However, all of these large databases and analyses are sufficiently disparate resulting in a variety of interpretations that are not in line with this most positive one.

There are some very important items that may be missing from this analysis. When one looks at the whole population of patients treated for breast cancer in Ontario, there are nearly 80% that received radiation therapy. This certainly is an important treatment for breast cancer, but it may reveal the reason why treated patients had a higher risk of IHD in long-term follow-up than HF. It is certainly a known fact that left-sided radiation in particular would raise the risk of IHD, and the medical era in which radiation therapy was delivered may be an important determinant of absolute risk for IHD (5). Whether or not simple techniques, such as a prone position or the breath-hold technique, could have had a major impact on the rate of IHD is uncertain (6). This information is not provided in this report. Even more importantly, the simplest, most effective method for prevention of IHD—aspirin—is not detailed in the concomitant medications. Although there may be debate about the effect of aspirin for the prevention of cancer or even IHD, especially in women, there is no debate about the usefulness of aspirin for the prevention of cardiac events in those who have IHD (7). One certainly could wonder if aspirin would be protective in women at high risk for the development of IHD (such as women receiving left-sided breast irradiation).

Taken together, these data presented here provide a lot of motivation to those concerned about cardio-oncology. With appropriate screening and treatment of cardiac risk factors, the rate of HF, despite cardiotoxic therapy, is encouragingly low. The rate of IHD is actually higher and makes up a substantial population of those admitted for cardiac reasons. It is still unknown if radiation therapy as a treatment for breast cancer promoted the development of IHD. Additionally, the knowledge as to the usefulness of a simple modification in the medical regimen like aspirin may actually prevent such a complication is undetected. Despite this, I am still quite optimistic that further studies like this one can reveal optimal prevention strategies. In the end, we collectively have to take a step back, see the whole picture, and make sure to “check our blind spots.”

Notes

Affiliation of author: Washington University in St Louis, St Louis, MO (DJL).

Dr Lenihan reports no disclosures directly related to this editorial but does have modest consultant agreements with Roche, Bristol Myers Squibb, Pfizer, Takeda, Prothena, Boehringer Ingelheim, and Akcea.