From the Journals

Herceptin linked to doubling of HF risk in women with breast cancer

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It may be time to move past a single screening regimen

While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.

These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.



Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.

The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.

The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.

While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).

According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.

The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.

Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).

For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.

The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.

Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).

The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).

Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.

After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)

The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”

Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.

An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.

“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.

However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”

The researchers also noted that the findings suggest that screening has become more common in recent years.

“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”

The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.

SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.

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