Background: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure and ischemic heart disease in women diagnosed with breast cancer.Methods: A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001-2008 in the Stockholm-Gotland region and followed-up until 2017. Time-dependent risks of arrhythmia, heart failure and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.Results: Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR=1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following loco-regional radiotherapy.Conclusions: Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.Funding: This work was supported by the Swedish Research Council [grant no: 2018-02547]; Swedish Cancer Society [grant no: CAN-19-0266] and FORTE [grant no: 2016-00081].

Background: Clinical trials have shown that adjuvant hormone therapy (AHT)–related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. Patients and Methods: By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. Results: Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11–2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21–1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41–2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39–2.35) or died from cancer (HR, 1.71; 95% CI, 1.37–2.12). Conclusions: AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.

Clinical guidelines have recommended high-risk breast cancer patients to extend adjuvant hormone therapy beyond 5 years. However, the prevalence, predictors, and outcomes of extended adjuvant hormone therapy in the real world remain unknown. By linking six Swedish health registries, we prospectively followed 13168 breast cancer patients (2005-2020) from their first prescription of tamoxifen or aromatase inhibitors, and categorized them as extending or not extending adjuvant hormone therapy. Cox regression analysis was used to investigate whether extended therapy was associated with breast cancer outcomes. Among breast cancer patients who were recommended to extend adjuvant hormone therapy by the national guidelines, the proportion of women who extended therapy increased 5 fold during the past 10 years, reaching 80.9% during 2018-2020. Patients were more likely to extend therapy after completing 5-year adjuvant hormone therapy if they were young (< 40 vs ≥ 65 years: OR, 1.71; 95% CI, 1.13-2.58), had positive lymph nodes (OR, 2.25; 95% CI, 1.85-2.73), had high tumor grade (grade 3 vs 1: OR,1.79; 95% CI, 1.34-2.39), received chemotherapy (OR, 5.22; 95% CI, 4.19-6.50), had first-degree relatives who died from breast cancer (OR, 1.84; 95% CI, 1.21-2.81), or had a high income (OR, 1.23; 95% CI, 1.01-1.49). Extended use of adjuvant hormone therapy was statistically significantly associated with improved disease-free survival (HR, 0.72; 95 CI%, 0.55-0.95). This study provides real-world evidence showing the use and improved breast cancer outcomes of extended adjuvant hormone therapy beyond 5 years.

<div>Abstract<p>Clinical guidelines have recommended patients with high-risk breast cancer to extend adjuvant hormone therapy beyond 5 years. However, the prevalence, predictors, and outcomes of extended adjuvant hormone therapy in the real world remain unknown. By linking six Swedish health registries, we prospectively followed 13,168 patients with breast cancer (2005–2020) from their first prescription of tamoxifen or aromatase inhibitors and categorized them as extending or not extending adjuvant hormone therapy. Cox regression analysis was used to investigate whether extended therapy was associated with breast cancer outcomes. Among patients with breast cancer who were recommended to extend adjuvant hormone therapy by the national guidelines, the proportion of women who extended therapy increased 5 folds during the past 10 years, reaching 80.9% during 2018 to 2020. Patients were more likely to extend therapy after completing 5-year adjuvant hormone therapy if they were young [40 vs. ≥65 years: OR, 1.71; 95% confidence interval (CI), 1.13–2.58], had positive lymph nodes (OR, 2.25; 95% CI, 1.85–2.73), had high tumor grade (grade 3 vs. 1: OR, 1.79; 95% CI, 1.34–2.39), received chemotherapy (OR, 5.22; 95% CI, 4.19–6.50), had first-degree relatives who died from breast cancer (OR, 1.84; 95% CI, 1.21–2.81), or had a high income (OR, 1.23; 95% CI, 1.01–1.49). Extended use of adjuvant hormone therapy was statistically significantly associated with improved disease-free survival (HR, 0.72; 95 CI%, 0.55–0.95). This study provides real-world evidence showing the use and improved breast cancer outcomes of extended adjuvant hormone therapy beyond 5 years.</p>Significance:<p>The proportion of patients with breast cancer extending adjuvant hormone therapy beyond 5 years has increased dramatically in recent years, which is associated with improved patient outcomes.</p></div>

BACKGROUND: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients.<br />OBJECTIVES?This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure and ischemic heart disease in women diagnosed with breast cancer.<br /> METHODS: A register-based matched cohort study was conducted including 8338 breast cancerpatients diagnosed from 2001-2008 in the Stockholm-Gotland region and followed-up until 2017. Overall and time dependent risks of arrhythmia, ischemic heart disease and heart failure in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.<br />RESULTS: During a median follow-up of 10.8 years, the hazard ratios for arrhythmia, heart failure and ischemic heart disease, were 1.27 (95% CI = 1.18-1.37), 1.38 (95% CI = 1.23-1.55), and 0.93 (95% CI = 0.84-1.03), respectively. Time-dependent analyses revealed long-term increased risks of arrhythmia, and heart failure in breast cancer patients compared to matched controls. The risk of ischemic heart disease was only elevated in the first year after cancer diagnosis. Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following loco-regional radiotherapy.<br />CONCLUSIONS: Administration of systemic adjuvant therapies appear to be associated with increased risks of heart disease. The risk estimates observed in this study may serve as reference to aid adjuvant therapy decision-making and patient counseling in oncology practices.

Background: Clinical guidelines have recommended breast cancer patients with certain characteristics to extend their therapy after 5-year adjuvant hormone therapy. However, no study thus far has described the prevalence, predictors, and outcomes of extending adjuvant hormone therapy in the real world. Methods: We identified 2,937 breast cancer patients who completed 5-year adjuvant hormone therapy during 2010-2019 in Stockholm, Sweden, by linking the Quality Register for Breast Cancer, Prescribed Drug Register, and Cause-of-death Register. We followed them until September 2020. Extended adjuvant hormone therapy was defined as having at least 2 prescriptions of tamoxifen and/or aromatase inhibitors after completing 5-year therapy. We used logistic regression to examine predictors of extended adjuvant hormone therapy and Cox regression to examine whether extended therapy is associated with distant metastasis-free survival, disease-free survival and all-cause mortality. Results: The proportion of extending therapy after 5-year adjuvant hormone therapy increased by 7 times during the past decade, from 8.8% in 2010 to 63.7% in 2019. Predictors of extended adjuvant hormone therapy included young age (≤50 years) at extension, positive lymph node status, high tumor grade and chemotherapy, among which chemotherapy was the strongest predictors [adjusted hazard ratio (HR), 4.64 (95% CI, 3.64-5.92)]. Among patients with chemotherapy, extended therapy improved distant metastasis-free survival [adjusted HR, 0.34 (95 CI%, 0.15-0.78)] and disease-free survival [adjusted HR, 0.61 (95 CI%, 0.39-0.95)]. Therapy discontinuation rates were similar during the first and second five years. Conclusion: Increasing number of breast cancer patients are extending adjuvant hormone therapy, even among patients without clear recommendations in clinical guidelines. Our findings support extended adjuvant hormone therapy in breast cancer patients with chemotherapy. Citation Format: Erwei Zeng, Wei He, Jenny Bergqvist, Kamila Czence. Extending therapy after 5-year adjuvant hormone therapy in breast cancer patients: A population-based study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-04.

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ImportanceA large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy.ObjectiveTo examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy.Design, Setting, and ParticipantsThis population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022.ExposureDiscontinuation of adjuvant hormone therapy.Main Outcomes and MeasuresThe main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy.ResultsA total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results.Conclusions and RelevanceIn this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.