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Contemporary breast cancer radiotherapy may up HF risk in older women

Jairia Dela Cruz
19 Apr 2017

Older women undergoing contemporary breast cancer radiotherapy may develop heart failure (HF) after a few years, with the risk of HF increasing in proportion to cardiac radiation dose, according to a study.

The study included 170 breast cancer patients (mean age at contemporary [1998 to 2013] conformal radiotherapy, 69 years), of which 59 had HF. Majority of HF patients had preserved ejection fraction (EF; 64 percent) or had midrange EF (EF ≥40 percent; 50 of the 56 HF patients with an EF measurement). The mean interval from radiotherapy to HF diagnosis was 5.8 years. [Circulation 2017;135:1388–1396]

When cardiac radiation exposure was calculated, the mean cardiac radiation dose (MCRD) appeared to be significantly higher in HF patients than in non-HF controls (3.3 vs 2.1 Gy; p=0.004); the overall mean MCRD was 2.5 Gy. HF risk increased with higher calculated MCRD, and the odds ratios (ORs) per log MCRD were 9.1 (95 percent CI, 3.4 to 24.4) for any HF, 16.9 (3.9 to 73.7) for heart failure with preserved ejection fraction (HFpEF), and 3.17 (0.8 to 13.0) for HF with reduced EF.

HF risk was also higher in patients with more advanced disease (stage II to III; OR, 4.63; 1.45 to 14.78) and in those with a history of ischaemic heart disease (OR, 5.06; 1.34 to 19.13) or atrial fibrillation (OR, 3.41; 1.36 to 8.55).

“The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumour side,” researchers said.

Noting the small percentage (18.6 percent) of women who developed ischaemic events between radiotherapy and HF diagnosis, researchers said, “myocardial infarction due to epicardial coronary disease was not the predominant mediator of incident HF.”

“These data suggest that cardiac dose and HF risk factors should be considered in decisions about breast cancer radiotherapy and underscore the importance of techniques for reducing cardiac dose,” they continued.

They pointed out that existing radiotherapy techniques that allow reduction of cardiac exposure are inconsistently used. Indeed, in a previous meta-analysis, average and maximal cardiac doses of contemporary breast cancer radiotherapy studies substantially exceed those observed in the current study. [Int J Radiat Oncol Biol Phys 2015;93:845–853]

The present study, while potentially limited by the small sample size and the lack of data on specific cardiac chamber doses, among others, provides “further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF,” researchers said.

In an accompanying editorial, Drs Juan Carlos Plana from the Texas Heart Institute at Baylor St. Luke’s Medical Center and Ana Barac from the MedStar Washington Hospital Center commented that the findings of the current study present both good news and bad news. [Circulation 2017;135:1413–1416]

“The good news is that oncologists have done a great job treating breast cancer. The bad news is that cardiovascular disease is emerging as the most important competing mortality risk in women with early stage breast cancer,” they said.

Shining a spotlight on the detailed exploration of the HF outcome, Drs Plana and Barac said the study offered novel insights in defining CV risk with radiotherapy.  

“Indeed, the majority of patients had preserved or mildly reduced EF (LVEF >40 percent), leading the authors to propose coronary microvascular endothelial inflammation with rarefaction and fibrosis as the underlying mechanisms linking therapeutic radiation to HF with preserved ejection fraction,” they said.

“[Such] conceptual framework importantly acknowledges the relevance of comorbidities often seen in older patients with breast cancer and raises the hypothesis that even low doses of contemporary radiation synergize with existing subclinical myocardial disease manifest as overt HF,” they continued.

Additionally, the study provides an example of successful measurement of heart exposure-reducing strategies and identifies HF with preserved EF as an important radiation-associated risk for the clinician to be aware of and for the investigators to validate in other cohorts, Drs Plana and Barac said.

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