Cardiology Care Ups CV Monitoring, BP Control in HER2+ Breast Cancer

Patrice Wendling

June 18, 2020

Specialty care from a cardiologist may confer clinical benefits for women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab (Herceptin, Genentech/Roche), a new study suggests.

Over 48 months of follow-up, results showed cardiology involvement prior to starting trastuzumab was associated with a higher rate of guideline-recommended cardiovascular (CV) monitoring and better systolic blood pressure (BP) control.

Trastuzumab is commonly used to treat HER2-positive breast cancer, which accounts for 20% of all breast cancers. But it carries a boxed warning for decreased left ventricular ejection fraction and heart failure (HF), and interval monitoring with echocardiography is recommended for all patients receiving the monoclonal antibody.

For the study, investigators analyzed electronic health records from 1047 patients (mean age, 54 years) who received trastuzumab between January 2009 and July 2018 in the University of Pennsylvania health system, Philadelphia. Anthracyclines were used as part of treatment in 15%.

Guideline-adherent cardiovascular monitoring was defined as echocardiography assessment in the 4 months before the initiation of trastuzumab and at least every 4 months during therapy.

Overall, 28% of patients visited a cardiology or cardio-oncology provider beginning 3 months before the baseline visit until the last contact date, the authors report June 16 in JACC: CardioOncology.

Pre-existing HF, atrial fibrillation, and anthracycline treatment were independently associated with a cardiology visit either at baseline or during follow-up.

Patients who interacted with cardiologists, compared with those who did not, had more guideline-adherent cardiac monitoring (76.4% vs 60.1%; P = .007) and cardiac biomarker testing with troponin or N-terminal pro-B-type natriuretic peptide (27.8% vs 13.8%; P = .001).

The use of guideline-adherent cardiac monitoring was 36% to 46% in previous studies of patients with breast cancer treated with adjuvant trastuzumab-based therapy, the authors note.

Among the 5815 echocardiographic procedures for which data on provider specialty were documented, most of the orders were authorized by oncologists (~84% in those with no cardiology involvement and ~79% in those with cardiology involvement before trastuzumab initiation).

CV Risk Parameters

Cardiology involvement was associated with an average 1.5 mm Hg lower systolic BP, independent of baseline systolic BP and antihypertensive medication use (95% CI, –2.9 to –0.1; P = .035).

The effect size was greater in patients with baseline hypertension, who had an average 2.7 mm Hg drop in systolic BP (95% CI, –4.6 to –0.7; P = .007) and were more likely to attain a target systolic BP below 140 mm Hg (odds ratio, 1.36; 95% CI, 1.06 to 1.74; = .016).

Body mass index (BMI) did not budge significantly in the overall population when cardiologists were involved, but dropped 0.5 kg/m2 in women who were overweight or obese at baseline.

"I think the results are encouraging," senior author Bonnie Ky, MD, MSCE, University of Pennsylvania, told | Medscape Cardiology. "These are modest changes but they are significant."

These types of changes have been associated with significant reductions in cardiovascular disease risk over time in larger clinical trials, she noted. For example, a 2 mm Hg reduction in systolic BP has been linked to a 10% reduction in stroke mortality and a 7% reduction in ischemic heart disease mortality in middle-aged adults.

"We do think they are important and speak to more aggressive risk factor modification under the care of a specialist," said Ky, who is also editor-in-chief of JACC: CardioOncology.

This broader role for cardiologists is particularly important given the burden of pre-existing CVD and CVD risk factors in patients with cancer and survivors. In the study, the baseline prevalence of hypertension was 40.6%, dyslipidemia 23.1%, HF 3.2%, atrial fibrillation 1.7%, and diabetes 5.9%.

"Ideally collaboration between cardiology and oncology can improve the ability to cure a patient's cancer while minimizing the risk of adverse cardiovascular occurrences," Erica L. Mayer, MD, MPH, Dana-Farber Cancer Institute, Boston, told | Medscape Cardiology. "Optimization of all cardiovascular parameters, including blood pressure, lipids, and weight, may allow a patient to protect her heart health while becoming a healthy cancer survivor."

Asked about the 28% cardiology involvement at a US cancer center with one of the most well-developed cardio-oncology programs, she said "the linkage with pre-existing cardiovascular conditions, as well as the likelihood of low incidence of cardiovascular disease, in the study population may have led to what appears to be a lower percentage of patients interacting with cardiology at baseline."

In an accompanying editorial, Mayer says a case can be made from the findings that patients with pre-existing CV disease or at high risk for adverse CV events with cancer therapy should receive multidisciplinary care that involves a cardiologist. "However, for young, otherwise healthy patients with breast cancer with few or no cardiovascular risk factors, the benefits of [additional] subspecialty care may be less clear."

Further, the rationale supporting the recommended frequency of cardiac monitoring may not be as "compelling" in this group, given the very low incidence of baseline cardiac dysfunction or cardiac events, particularly when treated with nonanthracycline regimens, she writes.

The findings are a call for further study and more personalized medicine, agreed Ky.

"I think there's a need absolutely for established guidelines and/or expert consensus statements about who should be referred, so patients can be referred more systematically," she said. "Referral to cardiologists, however, is certainly a function of risk factors. Part of the challenge is identifying who will derive the most benefit from cardiovascular care.

"There are some obvious cases: patients with heart failure and patients with pre-existing cardiovascular disease should be under the regular care of a cardiologist," Ky added. "But there's certainly a grey zone, especially as it relates, for example, to patients with hypertension and cardiovascular risk factors. It's not a one-size-fit-all, and I believe it is a matter of defining who is at increased CV risk and who would derive the greatest clinical benefit."

Researchers at the University of Pennsylvania have developed a clinical risk-prediction algorithm and are investigating both clinical- and biomarker-guided strategies to identify and treat patients at greatest risk of developing left ventricular declines and cardiac dysfunction with exposure to cancer therapies. "These studies are one step forward but they will all need to be externally validated," Ky said.

Ky and Mayer reported having no relevant conflicts of interest.

JACC: CardioOncol. 2020;2:179-189, 190-192. Full text, Editorial

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