Characteristics and Outcomes of Women Developing Heart Failure After Early Stage Breast Cancer Chemotherapy: A Population-Based Matched Cohort Study

Abstract

Background: The prognosis of heart failure (HF) after early stage breast cancer (EBC) treatment with anthracyclines or trastuzumab is not well-characterized. Methods: Using administrative databases, women diagnosed with HF after receiving anthracyclines or trastuzumab for EBC in Ontario during 2007 to 2017 (the EBC-HF cohort) were categorized by cardiotoxic exposure (anthracycline alone, trastuzumab alone, sequential therapy with both agents) and matched on age with ≤3 cancer-free HF controls to compare baseline characteristics. To study prognosis after HF onset, we conducted a second match on age plus important HF prognostic factors. The cumulative incidence function was used to describe risk of hospitalization or emergency department visits (hospital presentations) for HF and cardiovascular death. Results: A total of 804 women with EBC developed HF after anthracyclines (n=312), trastuzumab (n=112), or sequential therapy (n=380); they had significantly fewer comorbidities than 2411 age-matched HF controls. After the second match, the anthracycline-HF cohort had a similar 5-year incidence of HF hospital presentations (16.5% [95% CI, 12.0%–21.7%]) as controls (17.1% [95% CI, 14.4%–20.1%]); the 5-year incidence was lower than matched controls for the trastuzumab-HF (9.7% [95% CI, 4.7%–16.9%]; controls 16.4% [95% CI, 12.1%–21.3%]; P =0.03) and sequential-HF cohorts (2.7% [95% CI, 1.4%–4.8%]; controls 10.8% [95% CI, 8.9%–13.0%]; P <0.001). At 5 years, the incidence of cardiovascular death was 2.9% (95% CI, 1.2%–5.9%) in the anthracycline-HF cohort vs. 9.5% (95% CI, 6.9%–12.6%) in controls, and 1.7% (0.6%–3.7%) for women developing HF after trastuzumab vs. 4.3% (95% CI, 3.1–5.8%) for controls. Conclusions: Women developing HF after cardiotoxic EBC chemotherapy have fewer comorbidities than cancer-free women with HF; trastuzumab-treated women who develop HF have better prognosis than matched HF controls.

Evaluation of Risk Prediction Models to Identify Cancer Therapeutics Related Cardiac Dysfunction in Women with HER2+ Breast Cancer

“…The NSABP-31 CRS predicted the probability of "definite or probable cardiac death or congestive heart failure (CHF) manifested by dyspnea with normal activity or at rest and associated with an absolute decrease in LVEF of greater than 10 percentage points from baseline to a value less than 55% or a decrease of more than 5% to a value below the lower limit of normal". The majority of the cardiac outcomes in this study (95%) occurred within the first 2 years [18].…”

“…To potentially promote more clinical uptake of these models, we sought to assess and compare the performance of these models in a large cohort of women with HER2+ breast cancer treated in a routine clinical practice. We focused on the diagnosis of CTRCD by the end of treatment, as this can affect ongoing cancer treatment and majority of CTRCD events in women with HER2+ early-stage breast cancer occur by the end of the treatment [4,11,18,24]. In our cohort, the NSABP-31 CRS and the HFA-ICOS proformas appear to identify patients with graded risk for CTRCD with the highest risk categories having a 1.7-to-2.4-fold higher risk of CTRCD compared to the lowest risk category.…”

Stress cardiomyopathy in hospitalized patients with cancer: machine learning analysis by primary malignancy type

“…34 A more recent 2021 study showed that women with breast cancer developing heart failure (HF) after trastuzumab-based chemotherapy had a lower risk of HF hospital presentations than patients with HF and no cancer. 35 This result was likely driven by the fact that the cohort of patients with breast cancer had fewer co-morbidities despite a diagnosis of malignancy. Moreover, in our study, in patients with breast cancer and SC, a historical diagnosis of breast cancer was far more prevalent than a diagnosis of active cancer (Figure 1).…”

“…A large study of NIS patients in 2018 showed that the diagnosis of breast cancer in patients undergoing PCI was not significantly associated with either in‐hospital mortality or any of the complications studied 34 . A more recent 2021 study showed that women with breast cancer developing heart failure (HF) after trastuzumab‐based chemotherapy had a lower risk of HF hospital presentations than patients with HF and no cancer 35 . This result was likely driven by the fact that the cohort of patients with breast cancer had fewer co‐morbidities despite a diagnosis of malignancy.…”

Clinical Characteristics, Treatment, and Short-Term Outcome in Patients with Heart Failure and Cancer

“…However, the number of patients was small, and it may be the reason for the lack of statistically significant differences in mortality between cancer and noncancer populations. There are also observations in which trastuzumab-treated women who developed heart failure had better prognoses than matched heart failure controls-patients with no cancer [ 15 ].…”