April 17, 2019
3 min read

Ischemic heart disease driver of cardiovascular hospitalizations after early-stage breast cancer

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Women with early-stage breast cancer had a significantly greater risk for cardiovascular disease hospitalizations than women without cancer, with ischemic heart disease representing the most common reason for hospitalization, according to results of a population-based matched cohort study published in Journal of the National Cancer Institute.

Results also showed risk factors other than chemotherapy frequently preceded hospitalizations for heart failure among this patient population.

“Despite increasing concern about cardiovascular disease after early-stage breast cancer, most cardio-oncology research has focused on heart failure using outcome definitions based on outpatient recognition of reduced left ventricular ejection fraction,” Husam Abdel-Qadir, MD, PhD, FRCPC, of the cardiology clinic at Women’s College Hospital in Toronto, and colleagues wrote. “There are fewer data on clinically overt [heart failure] requiring hospital-based care, which are necessary to better understand the impact of [heart failure] on cancer survivors.”

Abdel-Qadir and colleagues analyzed hospitalizations and ED visits through March 2017 among 78,318 Ontario women diagnosed with early-stage breast cancer between April 2005 and March 2015. Researchers matched each woman with three cancer-free controls (n = 234,954) born the same year (median age of patients and controls, 61 years; interquartile range [IQR], 51-72).

Of those with early-stage breast cancer, more than one-third (n = 28,950) had documented use of anthracyclines or trastuzumab (Herceptin, Genentech), and almost two-thirds (n = 51,145) had documented radiation therapy.

Median follow-up for the breast cancer cohort was 5.7 years (IQR, 3.5-8.4).

Results showed the 10-year rate of cardiovascular disease hospitalization was 10.8% (95% CI, 10.5-11.1) after early-stage breast cancer — most often due to ischemic heart disease — and 9.1% (95% CI, 8.9-9.2) among controls.

The cause-specific HR for cardiovascular disease hospitalization among women with early-stage breast cancer vs. controls was 1.15 (95% CI, 1.11-1.18) after accounting for baseline characteristics.

Ischemic heart disease represented the most common first cardiovascular disease hospitalization event in both groups, with a 5-year cumulative incidence of 2.7% (95% CI, 2.5-2.8%). Among cardiotoxin-exposed women, the 10-year cumulative incidence of ischemic heart disease was 1.6% (95% CI, 1.4-1.7).

After regression adjustment, patients with early-stage breast cancer were significantly more likely than controls to be hospitalized for heart failure (HR = 1.21; 95% CI, 1.14-1.29), arrhythmias (HR = 1.31; 95% CI, 1.23-1.39) and cerebrovascular disease (HR = 1.1; 95% CI, 1.04-1.17).

Most women with early-stage breast cancer who presented to the hospital with heart failure had a predisposing risk factor, the most common of which included age older than 60 years (87.2%), hypertension (81.5%) and diabetes (39.7%). Only 2.9% of women with a heart failure hospitalization after early-stage breast cancer group did not have recognizable risk factors.


Study limitations cited by researchers included that patients with early-stage breast cancer are more likely to be documented with pre-existing cardiovascular disease and risk factors than cancer-free control subjects, so comparing pretreatment data between the two groups may be biased.

“Women with [early-stage breast cancer] had a higher risk of hospitalization for most categories of [cardiovascular disease] compared with age-matched, cancer-free women despite a higher competing risk from death,” Abdel-Qadir and colleagues wrote. “The absolute risk was highest for ischemic heart disease, rather than [heart failure], even for cardiotoxin-exposed women.”

The study implies that incidence of heart failure may not be very high among patients treated for early-stage breast cancer. However, certain factors are missing in this analysis, specifically consideration of the fact that nearly 80% of patients received radiation therapy, which could explain the risk for ischemic heart disease in patients later in life, Daniel J. Lenihan, MD, FACC, director of the Cardio-Oncology Center of Excellence at Washington University School of Medicine in St. Louis and professor of medicine in the division of cardiovascular diseases at Washington University School of Medicine, wrote in a related editorial.

“This certainly is an important treatment for breast cancer, but it may reveal the reason why treated patients had a higher risk of ischemic heart disease in long-term follow up than [heart failure],” Lenihan wrote. “It is certainly a known fact that left-sided radiation in particular would raise the risk of ischemic heart disease, and the medical era in which radiation therapy was delivered may be an important determinant of absolute risk for ischemic heart disease.” – by John DeRosier

Disclosures: The study authors report no relevant financial disclosures. Lenihan reports advisory roles with Akcea, Boehringer, Bristol-Myers Squibb, Ingelheim, Pfizer, Prothena, Roche and Takeda.