A retrospective, non-interventional study of breast cancer patients diagnosed with ER+/HER2 negative, locally advanced or metastatic breast cancer treated with palbociclib in Denmark.

BACKGROUND: The recommended first-line treatment for advanced, ER+/HER2 negative breast cancer is a CDK 4/6 inhibitor in combination with an endocrine backbone. This study investigated the use of palbociclib, as first- or second-line therapy for advanced breast cancer patients in a real-world setting. MATERIAL AND METHODS: This retrospective, population-based study included all Danish, advanced breast cancer patients with ER+/HER2 negative disease who initiated first- or second-line treatment with palbociclib from January 1st, 2017, until December 31st, 2020. The primary outcomes were PFS and OS. RESULTS: The study included 1054 advanced breast cancer patients with a mean age of 66.8 years. Median OS was 51.7 months (95% CI, 44.9-54.6) for all patients in the first-line setting (n = 728) and median PFS was 24.3 months (95% CI, 21.7-27.8). Patients treated in second line (n = 326) had a median OS of 32.5 months (95% CI, 29.9-35.9) and a median PFS of 13.6 months (95% CI, 11.5-15.7). In first-line setting, the PFS and OS were significantly different for endocrine sensitive patients treated with AI (aromatase inhibitor) (n = 423) vs. fulvestrant (n = 158) as endocrine backbone to palbociclib (median PFS AI 31.3 months vs fulvestrant 19.9 months, p = 0.002 and median OS AI 56.9 months vs. fulvestrant 43.6 months, p = 0.001). In endocrine resistant patients (n = 145), no statistically significant difference in PFS was shown (median PFS AI 21.5 months vs. fulvestrant 12.0 months, p = 0.09), whereas OS was significantly different (median OS AI 43.5 months vs. fulvestrant 28.8 months, p = 0.02). CONCLUSION: In this real-world study, treatment with palbociclib combination therapy met the standards of efficacy set by the phase III trials, PALOMA-2 and PALOMA-3, and the standards set by real-world studies in other countries. The study showed significantly different outcomes in terms of PFS and OS in endocrine sensitive patients comparing AI vs. fulvestrant as endocrine backbone to palbociclib as first-line therapy.

Improvements in Survival and Early Retirement Rates - Real-World Evidence on Danish Breast Cancer Patients 2004-2018.

Background: Historically, Denmark has had poor survival for cancer patients relative to other western countries with comparable health-care systems. In this study, we examine the long-term cancer impact of a nationwide reform addressing all cancer diagnostics, implemented in 2006. The analyses include patients diagnosed with breast cancer and their spouses (informal caregivers). Patients and their spouses diagnosed before and after the reform were compared. Focus is on the potential impact on overall survival, early retirement, sick leave, unemployment as well as earnings (income). Methods: In a nationwide retrospective cohort study utilizing the Danish National Patient Register we identified 77,474 breast cancer patients between 1st January 2002 and 31st December 2018. Data was merged with the National Cancer Register, the Central Person Register, the Education Register, the DREAM Register and the Income Register using citizens' personal identification number. Spouses of cancer patients were identified through the Central Person Register. Propensity score matching was applied to match populations before and after the reform. Analyses on matched as well as unmatched populations were performed. Results: In a matched sample, risk of mortality was reduced by 15% for breast cancer patients diagnosed after the reform. Moreover, there was a 15% reduced risk of early retirement. The patients diagnosed after the reform had reduced income three to five years after diagnosis relative to those diagnosed before the reform, likely due to survival bias and labor market conditions. In an unmatched sample of patients diagnosed two years before or after the reform, mortality was reduced by 7%. Conclusion: Implementation of the nationwide cancer reform together with advancement in new cancer treatments had a positive impact on survival and reduced risk of early retirement. The results from this study are reassuring that relevant health-care reforms improve cancer outcome.

Cardiovascular disease in women with breast cancer - a nationwide cohort study.

BACKGROUND: There is increasing concern about cardiovascular disease (CVD) after breast cancer (BC). The aim of this study was to estimate the prevalence of different types of CVD in women diagnosed with BC compared to cancer-free controls as well as the incidence of CVD after BC diagnosis. METHODS: We performed a cohort study based on data from national registries covering the entire Danish population. We followed 16,505 cancer-naïve BC patients diagnosed from 2003 to 2007 5 years before and up to 10 years after BC diagnosis compared to 165,042 cancer-free controls. RESULTS: We found that 15.6% of BC patients were registered with at least one CVD diagnosis in hospital records before BC diagnosis. Overall, BC patients and controls were similar with regard to CVD comorbidity before BC diagnosis. After BC diagnosis, the incidence of all CVD diagnoses combined was significantly higher in BC patients than controls up to approximately 6 years after the index date (BC diagnosis). After 10 years, 28% of both BC patients and controls (without any CVD diagnosis up to 5 years before the index date) had at least one CVD diagnosis according to hospital records. However, the incidence of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism remained higher in BC patients than controls during the entire 10-year follow-up period. After 10 years, 2.7% of BC patients compared to 2.5% of controls were diagnosed with heart failure, 2.7% of BC patients compared to 1.5% of controls were diagnosed with thrombophlebitis/thrombosis, and 1.5% of BC patients compared to 1.0% of controls were diagnosed with pulmonary heart disease according to hospital records. Furthermore, we found that the risk of heart failure and thrombophlebitis/thrombosis was higher after chemotherapy. CONCLUSIONS: Focus on CVD in BC patients is important to ensure optimum treatment with regard to BC as well as possible CVD. Strategies to minimise and manage the increased risk of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism in BC patients are especially important.

Mortality from cardiovascular disease in women with breast cancer - a nationwide registry study.

BACKGROUND: Only few existing studies have investigated the mortality from cardiovascular disease (CVD) in women with breast cancer (BC). The aim of this study was to investigate CVD mortality in patients with BC compared with a matched control group without BC using national registry data. MATERIAL AND METHODS: We followed 16,505 Danish women diagnosed with BC in 2003-2007 up to 10 years after BC diagnosis compared with 165,042 matched controls from the general Danish population. The matching criteria included gender, age, region of residence, and education. We performed multivariate Cox regression analyses to investigate the influence of preexisting CVD on mortality. Moreover, we used the cumulative incidence and conditional probability functions to study the risk of CVD-related death in the presence of competing risk, i.e., the risk of dying from other causes than CVD. RESULTS: We found that preexisting CVD increased both overall mortality and CVD mortality in both patients with BC and controls. Furthermore, we found that patients with BC were at lower risk of dying from CVD up to 10 years after BC diagnosis compared with controls. The cumulative incidence of CVD as underlying cause of death was 4.0% in patients with BC and 5.7% in controls after 10 years. The most common CVD-related causes of death were ischemic heart disease including acute coronary syndrome, cerebrovascular accident, heart failure, and atrial fibrillation. DISCUSSION: Our study contributes to the growing body of work on BC and comorbidities and highlights the importance of CVD in individuals with BC. Further studies are needed to confirm our finding that patients with BC are at lower risk of dying from CVD up to 10 years after BC diagnosis compared with a matched control group without BC.