Among breast cancer (BC) survivors aged 50 years and older, cardiovascular disease (CVD) accounts for 35% of noncancer-related deaths and is a leading cause of death. Drug toxicity from previously administered chemotherapeutic agents (such as anthracyclines or biological agents), lifestyle factors (such as physical inactivity, obesity, and alcohol use), and hormonal factors (for example, insulin resistance or endocrine therapy) contribute to the development of cardiovascular disease.
Several recent papers have looked at the relationship between BC and CVD mortality. CLUE II (Give Us a Clue to Cancer and Heart Disease) is a prospective, community-based longitudinal study of residents from Washington County, Maryland, that was implemented by Johns Hopkins Bloomberg School of Public Health in 1989. Using clinical characteristics and time since diagnosis (relative to age-matched cancer-free women), this trial sought to identify risk factors for all-cause and CVD-related mortality in women with BC.
Among the 3,768 women studied, 628 were BC survivors and 3,140 were cancer-free. For those with BC, the mean age at diagnosis was 64.5 years. Most patients with BC had ER-positive disease and were diagnosed at an early age. Post-menopausal status, mean BMI, smoking status, mean total cholesterol and blood pressure measurements were similar at baseline between survivors and cancer-free women.
Investigators found that over a median follow-up period of 10.4 years, all-cause mortality was almost two-fold higher in survivors compared with cancer-free women (hazard ratio = 1.79) after adjusting for age, menopausal status, education level, smoking status, alcohol intake, BMI, and hormone use. Similar results were seen when patients were stratified by tumor stage, ER status, and older age at diagnosis. The risk of death from any cause was not statistically significantly different in over 15 years of follow-up, except in older women, where it increased almost threefold at >15 years postdiagnosis (hazard ratio = 2.69).
CVD-related mortality was the second most common cause of death among BC survivors (20%) but the most frequent cause in cancer-free women (29%). Ischemic heart disease was the leading cause of CVD death. CVD death occurred after approximately 8 years of follow-up (hazard ratio = 1.65); the hazard ratio was 0.94 from years 0 through 8 years postdiagnosis. In older women, the hazard ratio was 2.24 for CVD-related mortality after 8 years.
The authors concluded that in BC survivors, there is an elevated risk of mortality compared with the general population, and this exists many years after BC diagnosis.
In another study, data from 164 women (mean age 67 years) from the Cardiovascular Disease outcomes among Breast Cancer Survivors study (CVDBCS), a cross-sectional study of noninstitutionalized BC survivors, were examined for the frequency of congestive heart failure, hypertension, myocardial infarction, cardiomyopathy, stroke, and venous thrombosis/thromboembolism in women diagnosed with stage I-IV BC and who had undergone primary therapy. Particular emphasis was placed on the risk of developing congestive heart failure following chemotherapy.
Two-thirds of the study population were Caucasian, and 30% were African Americans. The majority of women were in early stages of breast cancer: 19.8% in ductal carcinoma in situ, 26.8% in stage I, and 21% in stage II. Approximately 9 years had elapsed since the time of diagnosis at the time of the study. Over one-half (54.9%) of women had received chemotherapy with much fewer, 4.9%, having received a biological agent.
Among the study participants, approximately 63% were hypertensive, one-half had hypercholesterolemia, almost a quarter had a history of diabetes and 8.3% were current smokers. Approximately 5% and 6% had a history of congestive heart failure or stroke, respectively.
The authors found that time since BC diagnosis was a significant predictor of congestive heart failure (odds ratio = 1.14).
A third study used a statistical and machine-learning approach to evaluate 10-year risk of CVD outcomes in women with BC from a large midwestern medical center. This study was designed to investigate the association between cardiovascular health (CVH), cardiotoxic cancer treatments, age, race, and 10-year risk of post-treatment CVD and death. The electronic health record was used to obtain measures of CVH, which included smoking status, BMI, blood pressure, glucose/hemoglobin A1c, and cholesterol values; these were used to calculate CVH risk scores.
The 1,934 participants (average age 58.5 years) were stratified into three groups based on age of BC diagnosis (20-40 years, 41-60 years, 61-100 years). The potential adverse effects of chemotherapy, left-sided radiation, hormone-related or antiestrogenic therapy, and trastuzumab were studied. BC treatments were categorized into anthracyclines, hormone therapy, aromatase inhibitors, monoclonal antibodies, antimicrotubule agents, alkylating agents, antimetabolites, or other (e.g., bortezomib).
Researchers found that 20% of women were taking a cholesterol medication, 3% were current smokers, and about 18% had received any class of cardiotoxic cancer treatment. Among those who received a cardiotoxic regimen, 46% used an aromatase inhibitor and 26% had received hormone therapy. After 10 years of follow-up, one-third of this group had developed CVD and 19% had died. CVD disease increased with age and race with black women being at significantly greater risk compared with white women (48% vs. 31%, respectively). CVD was higher among those with lower CVH scores, indicating poorer CVH. Cardiotoxic cancer treatment was associated with an increased occurrence of posttreatment CVD. Incident CVD was 58.9% among those who received any cancer treatment compared with 29.1% among those who did not. Similar trends were seen for mortality with higher death rates seen among those who were older, of black race, received cancer treatments, and had a lower CVH score.
Low CVH scores along with exposure to cardiotoxic treatments had a synergistic effect on increasing risk of posttreatment CVD (75.9% vs. 20.8% of those who were not exposed to cardiotoxic treatments). Women with low CVH scores who were not exposed to cardiotoxic treatments and women with high CVH scores who were exposed to cardiotoxic treatments were also at increased risk of CVD but not nearly as high as those who had a low CVH score and had received cardiotoxic treatments. Similar trends were seen in mortality.
While all of these studies have limitations, they consistently point to an increased risk of CVD among BC survivors. Pharmacists are well qualified to help address risk factors for CVD disease in BC patients in order to help mitigate their detrimental effects.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
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