Breast Cancer And An Analysis of Cardiovascular Events
Breast cancer is considered one of the most common cancers in the world. In 2020, there are 7.8 million women diagnosed with breast cancer globally. It also has resulted in more than 700,000 deaths based on the data from WHO. Unlike other cancers that tend to happen later in life or due to lifestyle, breast cancer can occur to any woman at any age after puberty.
One of the biggest issues today in the field of medicine is that the treatments for breast cancer are “cardiotoxic”. One study revealed that there’s a huge risk increase in patients who survived breast cancer that later had deaths caused by cardiovascular causes. Findings also reveal that the risk of developing CVD is not only through aging but also through cardiotoxic treatments such as mediastinal radiotherapy, anthracycline-based chemotherapy, biological therapies, and hormonal therapy for breast cancer. This is even high for women who already have existing CVD risk factors.
Treatments that are known to increase cardiovascular risks
Anthracyclines are the primary chemotherapeutic agent for breast cancer patients. They are used for patients with low cardiovascular risk as they are known to have cardiotoxicity resulting in left ventricular dysfunction.
For patients with receptor-positive BC, endocrine therapy and HER2 blockade are the primary treatment along with chemotherapy. For pre-menopausal women, ovarian suppression in combination with an aromatase inhibitor is used as adjuvant endocrine therapy for high-risk patients that have received chemotherapy. However, these treatments have been found to suppress oestradiol which has several adverse metabolic effects. Patients are found to have various medical issues after taking the treatment including glucose intolerance, hyperglycemia, and hypertension. All of these are found to accelerate atherosclerosis and the development of cardiovascular and cerebrovascular diseases. All of these studies remain controversial and despite these results, the treatments are still being used today.
The Study
Since breast cancer’s link to a higher risk of cardiovascular events is still a debate, this study aims to add upon the existing literature that verifies or debunks the theory. Using data from hospitals in France, the researchers evaluated breast cancer and incident cardiovascular events in a contemporary population of female patients.
The study consists of female patients discharged from French hospitals from the year 2013. They all had at least 5 years of follow-up and without a history of major adverse cardiovascular events. Major adverse cardiovascular events include the following diseases: cancer (except BC), heart failure, ischemic stroke, myocardial infarction, and ischaemic stroke. After propensity score matching, patients with BC were matched 1:1 with patients with no BC. Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex, and smoking status at baseline.
Methods
Patient information such as demographics, a past matched cohort of women without breast cancer was collected. In contrast, they have a reduced risk of cardiovascular mortality, MI, and medical history and events during hospitalization or follow-up were described using data collected in the hospital records.
For each hospital stay, combined diagnoses at discharge were obtained. Each variable was identified using International Classification of Diseases, Tenth Revision (ICD- 10) codes, and BC was identified with its ICD- 10 codes (C50 and its subsections). Exclusion criteria were age <18 years.
No patients were actually physically involved in the study. The data of the study were also anonymised—due to this ethics approval specific to this study wasn’t needed. The French Data Protection Authority granted access to the PMSI data. Procedures for data collection and management were approved by the Commission Nationale de l’Informatique et des Libertés (CNIL), the independent National Ethical Committee protecting human rights in France, which ensures that all information is kept confidential and anonymous, in compliance with the Declaration of Helsinki.
Statistical analysis
Baseline characteristics that are binary variables are described as frequency and percentages and continuous variables as means (standard deviations [SDs]). Multivariate analyses were performed using a Cox model with all baseline characteristics, and hazard ratio(HR) was reported.
The model by Fine and Gray was also used for competing risks for (1) cardiovascular and noncardiovascular death, (2) MI and all-cause death, and (3) ischaemic stroke and all-cause death.
As the study is nonrandomized and to account for the presence of significant differences in baseline characteristics and control for potential confounders, propensity score matching was performed. Propensity scores were calculated using logistic regression with BC as the dependent variable.
For every female patient with BC, a propensity score-matched female patient with no BC was identified and selected with the one-to-one nearest neighbor method (with a caliper of 0.01 of the SD of the propensity score on the logit scale) and no replacement.
The distributions of demographic data and comorbidities in the two cohorts were assessed with standardized differences, which were calculated as the difference in the means or proportions of a variable divided by a pooled estimate of the SD of that variable with 5% or less indicating a negligible difference between the means of the two cohorts (Figure S1 and Figure S2).
Statistical significance was taken at p < 0.05. All analyses were performed using Enterprise Guide 7.1 (SAS Institute Inc., SAS Campus Drive, Cary, North Carolina, USA) and STATA version 16.0 (Stata Corp, College Station, TX).
Results:
A total of 1,795,759 patients were included in the study of which 64% had a history of breast cancer. Patients were followed up until 31 December 2019 to identify any occurrence of events.
During a mean follow-up of 5.1 years, matched female patients with BC had a higher risk of all-cause death, new-onset, major bleeding, and net adverse clinical events (NACE) including all-cause death, MI, ischaemic stroke, HF, or major bleeding compared with those with no BC.
The endpoints were evaluated using follow-up data starting from the date of their first hospitalization until the date of each specified outcome or date of last news in the absence of the outcome. Information on outcomes during the follow-up was obtained by analyzing the PMSI codes for each patient. Outcomes were identified using their respective ICD- 10, and the mode of death (cardiovascular or noncardiovascular) was identified based on the main diagnosis during hospitalization resulting in death.
Conclusion
The study of female patients in French hospitals with a history of breast cancer shows that women with a history of breast cancer have a higher risk of all-cause mortality, new-onset heart failure, and major bleeding compared to women without breast cancer.
The researchers recommend further studies to further investigate the cardiotoxic and cardioprotective impact of chemotherapeutic agents and how they can best be used to improve outcomes in high-risk patients.
Oncology Related Tools
Other
Latest Research
