Key result
Trastuzumab was associated with an increased risk of cardiac toxicity in elderly women with HER-2-positive breast cancer in cohort studies (HR 1.89; P<0.00001) and RCTs (HR 3.00; P<0.00001).
Why the study?
Does trastuzumab treatment increase the risk of cardiac toxicity in elderly women with HER-2-positive breast cancer?
Meta-Analysis (n=116,702)
Does trastuzumab treatment increase the risk of cardiac toxicity in elderly women with HER-2-positive breast cancer?
Hazard Ratio: 1.89 (95% CI 1.72–2.07)
p-value: p=< 0.00001
Trastuzumab treatment significantly increases the risk of cardiotoxicity in elderly women with HER-2-positive breast cancer, highlighting the need for careful cardiac monitoring, especially when combined with anthracyclines.
Supports enhanced cardiac monitoring in elderly HER2+ patients on trastuzumab; confirms elevated cardiotoxicity risk in meta-analysis of RCTs and cohorts.
BACKGROUND: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients. METHODS: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model. RESULTS: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% - 9.4) and 16.4% (95% CI 16.19% - 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 - 75), 71 (66 - 80+), 74.5 (65 - 89), 75 (66 - 81+) and 79.5 (60 - 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 - 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 - 1.87, p < 0.00001). CONCLUSION: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.
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Leung et al. (2015) conducted a meta-analysis in HER-2-positive breast cancer (n=116,702). Trastuzumab was evaluated on Defined cardiac toxicities (symptomatic congestive heart failure and CHF/HF/CM) (HR 1.89, 95% CI 1.72-2.07, p=< 0.00001). Trastuzumab was associated with an increased risk of cardiac toxicity in elderly women with HER-2-positive breast cancer in cohort studies (HR 1.89; P<0.00001) and RCTs (HR 3.00; P<0.00001).
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