Breast cancer mortality overall has substantially declined over the past three decades largely due to earlier detection and improved treatments, although the decline has been less pronounced among older as compared to younger women. With the reduction in mortality due to cancer, other causes contribute to a greater proportion of death in breast cancer patients, and recent reports indicate that cardiovascular disease (CVD) is now the leading cause of death in this patient population. However, the association between various CVD risk factors and survival has not been assessed in detail among breast cancer patients. Researchers from Dr. Joseph Unger’s group in the Division of Public Health Sciences at Fred Hutch recently published a paper in Journal of Clinical Oncology that reports the relationship between known CVD risk factors with survival and cardiac events in breast cancer patients.
Modifiable CVD risk factors, such as obesity, diabetes, high blood pressure, and elevated cholesterol are common comorbidities in cancer patients. Previous research has reported that these conditions are generally associated with poorer outcomes, such as cancer recurrence and worse survival, in breast cancer patients. In addition, some common cancer treatments are known to exert cardiotoxic effects that may exacerbate the risk for the development of CVD. Some research has suggested that older patients in particular may be more susceptible to the detrimental effects of anticancer therapies on cardiac health. However, research in this subset of patients is lacking, in part because older breast cancer patients are substantially under-represented in clinical trials.
Taken together, there is a knowledge gap of whether CVD risk factors may contribute to worse long-term survival in elderly breast cancer patients. To focus on the relationship between CVD risk factors and outcomes in older women, the authors utilized data collected from breast cancer phase II and III trials that were associated with SWOG, one of the largest of the National Cancer Institute-sponsored clinical trials networks.
Image provided by Dr. Joseph Unger
A novel component of the study was the use of Medicare claims information that was linked to the clinical trial records. This method allowed the authors to assess whether the research participants also had common CVD risk factors (obesity, diabetes, hypertension, hypercholesterolemia, and coronary artery disease or ischemic heart disease) at baseline. The primary study outcome was overall survival while secondary outcomes included progression-free survival, cancer-free survival, and the incidence of post-baseline cardiac events such as an acute ischemic event or acute heart failure. The authors successfully linked 1,460 breast cancer clinical trial participants 66 years of age or older to Medicare claims. The median participant age was 70 years and median follow-up time was 6 years. “This analysis is one of several recent studies that we have conducted using this innovative data linkage,” said Dr. Unger.
The authors found that in no case was the presence of any individual CVD risk factor associated with an increased risk of death. However, with each additional CVD risk factor, the risk of death increased by 23%. Progression-free survival was also worse with each additional factor, and there was a trend towards worse cancer-free survival, although this did not reach statistical significance.
Moreover, breast cancer patients with CVD risk factors at baseline experienced significantly more cardiac events (defined as acute ischemia or acute heart failure) during follow-up as compared to patients without risk factors. The risk for a cardiac event was increased by two-fold in diabetic patients and by more than two-fold in those with coronary artery disease. There was also a significant linear relationship between the number of CVD risk factors and risk for an eventual cardiac event. For example, as compared to patients with zero or one risk factor at baseline, the presence of two risk factors increased the risk by two-fold while the presence of three risk factors increased the risk by more than four-fold (see Figure).
The results from this study reveal that older breast cancer patients with adverse CVD risk factors are at an increased risk of cardiac events and death due to all causes. In highlighting the study results, Dr. Unger emphasized the unique methodology, “These findings are a great example of what can be accomplished using big data techniques combining trial data with Medicare claims to address novel research questions,” he said.
This research was supported by the National Cancer Institute.
Hershman DL, Till C, Shen S, Wright JD, Ramsey SD, Barlow WE, Unger JM. 2018. Association of cardiovascular risk factors with cardiac events and survival outcomes among patients with breast cancer enrolled in SWOG clinical trials. Journal of Clinical Oncology. doi:10.1200/JCO.2017.77.4414.