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Heart failure after treatment for breast cancer.

ABSTRACT: BACKGROUND:We aimed to develop dose-response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies. METHODS AND RESULTS:A case-control study was performed within a cohort of breast cancer survivors treated during 1980-2009. Cases (n =?102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation doses were estimated, and anthracycline doses and use of trastuzumab and endocrine therapy were abstracted from oncology notes. For HF cases who received radiotherapy, the estimated median mean heart dose (MHD) was 6.8 Gy [interquartile range (IQR) 0.9-13.7]. MHD was not associated with HF risk overall [excess rate ratio (ERR) = 1%/Gy, 95% confidence interval (CI) -2 to 10]. In patients treated with anthracyclines, exposure of ?20% of the heart to ?20?Gy was associated with a rate ratio of 5.7 (95% CI 1.7-21.7) compared to <10% exposed to ?20?Gy. For cases who received radiotherapy, median cumulative anthracycline dose was 247?mg/m2 (IQR 240-319). A dose-dependent increase was observed after anthracycline without trastuzumab (ERR = 1.5% per mg/m2 , 95% CI 0.5-4.1). After anthracycline and trastuzumab, the rate ratio was 34.9 (95% CI 11.1-110.1) compared to no chemotherapy. CONCLUSIONS:In absence of anthracyclines, breast cancer radiotherapy was not associated with increased HF risk. Strongly elevated HF risks were observed after treatment with anthracyclines and also after treatment with trastuzumab. The benefits of these systemic treatments usually exceed the risks of HF, but our results emphasize the need to support ongoing efforts to evaluate preventative strategies.

SUBMITTER: Boekel NB

PROVIDER: S-EPMC7137787 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Heart failure after treatment for breast cancer.

Boekel Naomi B NB Duane Fran K FK Jacobse Judy N JN Hauptmann Michael M Schaapveld Michael M Sonke Gabe S GS Gietema Jourik A JA Hooning Maartje J MJ Seynaeve Caroline M CM Maas Angela H E M AHEM Darby Sarah C SC Aleman Berthe M P BMP Taylor Carolyn W CW van Leeuwen Flora E FE

European journal of heart failure 20191112 2

<h4>Background</h4>We aimed to develop dose-response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies.<h4>Methods and results</h4>A case-control study was performed within a cohort of breast cancer survivors treated during 1980-2009. Cases (n = 102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation dos ...[more]

PMID: 31721395

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Project description:BackgroundThe use of trastuzumab has proven to be a successful strategy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, it is associated with an increased risk of cardiac dysfunction. We performed an up-to-date, comprehensive meta-analysis to clarify the risk of congestive heart failure (CHF) in patients with early breast cancer receiving different durations of adjuvant trastuzumab with the longest-term follow-up.MethodsEligible studies included randomized control trials of HER2-positive early breast cancer patients with or without trastuzumab in adjuvant chemotherapy. Adequate reporting of CHF data were required for inclusion. Statistical analyses were conducted to calculate the overall incidence, relative risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model.ResultsSix randomized control trials including 18,111 patients were identified. The overall incidence of high-grade CHF in patients treated with trastuzumab versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03-5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2 years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05-5.49) compared with control groups. No evidence of publication bias was observed.ConclusionAdjuvant trastuzumab therapy was strongly associated with an increased risk of significant CHF in patients with early breast cancer, particularly in 2-year use.Implications for practiceThis comprehensive meta-analysis evaluated the risk of congestive heart failure with a usage profile of adjuvant trastuzumab in patients with early breast cancer. Before initiating treatment with trastuzumab, a risk-benefit analysis for individual patients should be critically evaluated, considering that the prognosis is closely related to drug dose and duration of use. Cardiac function should be monitored throughout the treatment period and also during follow-up. Thus, early identification of trastuzumab-related cardiac dysfunction can allow effective medical intervention, elimination of symptoms, recovery of function, and continuation of trastuzumab therapy.

Project description:BackgroundHeart failure (HF) and breast cancer are 2 of the leading causes of death in postmenopausal women. The temporal association between HF and breast cancer in postmenopausal women has not been described.ObjectivesThis study sought to examine the temporal association between HF and breast cancer.MethodsPostmenopausal women within the WHI (Women's Health Initiative) cohort were studied. All prevalent HF and prevalent breast cancer at enrollment were self-reported. Incident hospitalized HF and breast cancer diagnoses were adjudicated through 2017.ResultsAmong a cohort of 44,174 women (mean age 63 ± 7 years), 2,188 developed incident invasive breast cancer and 2,416 developed incident hospitalized HF over a median follow-up of 14 and 15 years, respectively. When compared with a breast cancer- and HF-free cohort, there was no association between prevalent HF and incident invasive breast cancer and similarly, there was no association between prevalent breast cancer and incident hospitalized HF. Across the entire cohort, the median survival after incident hospitalized HF was worse compared with an incident invasive breast cancer diagnosis (5 and 19 years, respectively). In women with incident invasive breast cancer, prevalent HF was associated with an increased risk of mortality (hazard ratio: 2.28; 95% confidence interval: 1.31 to 3.95). In women with incident hospitalized HF, prevalent breast cancer was associated with an increased risk of mortality (hazard ratio: 1.66; 95% confidence interval: 1.03 to 2.68). Cause of death after incident HF was different only in women with prevalent and interim breast cancer compared with those without prevalent and interim breast cancer.ConclusionsIn postmenopausal women, prevalent HF was not associated with a higher incidence of breast cancer and vice versa. However, the presence of incident invasive breast cancer or incident HF in those with prevalent HF or prevalent breast cancer, respectively, was associated with increased mortality.

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Heart failure after treatment for breast cancer.

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Heart failure after treatment for breast cancer.

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