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- Kornalijnslijper-Altena, Renske, et al.
(författare)
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PREDIX II HER2 : Improving pre-operative systemic therapy for human epidermal growth factor receptor 2 (HER2) amplified breast cancer (BC)
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:15 Suppl.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neo-adjuvant systemic therapy (NAT) is the standard of care for most patients with early HER2-amplified and triple negative breast cancer (BC). Increasing the rate of pathological complete response (pCR) is highly meaningful for those patients, as pCR is strongly predictive for improved long-term disease-related outcomes. Clinical and preclinical evidence support the hypothesis that pCR-rates may be augmented by the addition of checkpoint inhibitors, such as monoclonal antibodies targeting the Programmed Death Ligand receptor 1 (PD-L1), to standard systemic NAT. Studies in different BC patient cohorts (e.g., IMPassion130, PANACEA, KATE2) have indicated that PD-L1 protein expression on tumor-infiltrating lymphocytes (TIL’s) is a predictive marker for checkpoint inhibitor efficacy.Methods: We have initiated a phase II open-label, 2:1 randomized clinical trial where women with early HER2-amplified, PD-L1+ BC (cT2-3 and/or cN+) are treated with standard NAT (composed of anti-HER2 antibodies with a chemotherapy backbone of sequentially taxanes + carboplatin and epirubicin + cyclophosphamide [EC]) +/- atezolizumab during EC. N = 190 patients will be accrued in nine centers in Sweden to be able to demonstrate a 20% increase in pCR-rate, with a power of 80% and a two-sided alpha of 10%. Firstly, a prescreening is performed to select patients with a PD-L1 expression of > 1% on TIL’s. Important exclusion criteria are significant organ dysfunction and (with some exceptions) active auto-immune diseases. Extensive translational side-studies are performed to explore predictive markers for treatment efficacy, including clinicopathologic studies, molecular imaging and microbiome analyses, as well as monitoring of acute and chronic treatment-related toxicity, objective cognitive function and quality of life. As of February 11th, 4 patients have been prescreened and 1 enrolled in the trial. The clinical trial registry number is NCT03894007.
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| 2. |
- Sund, Maria, 1983-, et al.
(författare)
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Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients : A population-based cohort study
- 2021
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Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 59, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors.METHODS: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy.RESULTS: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006-2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32-4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01-2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40-3.25 for arrhythmia; HR 2.03; 95% CI: 1.15-3.58 for ischemic heart disease).CONCLUSION: Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.
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| 3. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Lessons learned from an unsuccessful decentralized clinical trial in Oncology
- 2024
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Ingår i: npj Digital Medicine. - : Springer Nature. - 2398-6352. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Decentralized clinical trials have gained in popularity over the last years due to their advantages related to broadening recruitment strategies and resource saving possibilities. As more clinical trials adopt decentralized strategies, it is essential to share the knowledge about both successful and unsuccessful efforts in the research community. In the present commentary, we explore potential reasons that led to early termination of a decentralized clinical trial in Oncology.
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| 4. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Overall survival of patients with metastatic breast cancer in Sweden : a nationwide study
- 2022
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 127:4, s. 720-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers.Methods: This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS).Results: The total population consisted of 13,832 patients-2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC.Conclusion: This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.
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| 5. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Use of classifiers to optimise the identification and characterisation of metastatic breast cancer in a nationwide administrative registry
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:12, s. 1604-1610
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Tidskriftsartikel (refereegranskat)abstract
- Bakground: The prognosis for patients with metastatic breast cancer (MBC) is substantially worse when compared with patients with earlier stage disease. Therefore, understanding the differences in epidemiology between these two patient groups is important. Studies using population-based cancer registries to identify MBC are hampered by the quality of reporting. Patients are registered once (at time of initial diagnosis); hence only data for patients with de novo MBC are identifiable, whereas data for patients with recurrent MBC are not. This makes accurate estimation of the epidemiology and healthcare utilisation of MBC challenging. This study aimed to investigate whether machine-learning could improve identification of MBC in national health registries.Material and methods: Data for patients with confirmed MBC from a regional breast cancer registry were used to train machine-learning algorithms (or 'classifiers'). The best performing classifier (accuracy 97.3%, positive predictive value 85.1%) was applied to Swedish national registries for 2008 to 2016.Results: Mean yearly MBC incidence was estimated at 14 per 100,000 person-years (with 18% diagnosed de novo and 76% of the total with HR-positive MBC).Conclusion: To our knowledge, this is the first study to use machine learning to identify MBC regardless of stage at diagnosis in health registries covering the entire population of Sweden.
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| 6. |
- Zewenghiel, Luwam, et al.
(författare)
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Impact of body mass index on the efficacy of endocrine therapy in patients with metastatic breast cancer : A retrospective two-center cohort study
- 2018
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Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 40, s. 136-140
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Tidskriftsartikel (refereegranskat)abstract
- BAKGROUND: The aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant.METHODS: A consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified. The primary outcome of the study was time to disease progression (TTP) during the treatment with Fulvestrant in overweight and obese women compared to patient with normal BMI.RESULTS: In total, 173 patients were enrolled in the study cohort, amongst these, 141 patients received both Fulvestrant and AIs and 32 received only Fulvestrant. No statistical significant association was observed between the three BMI categories and TTP, during Fulvestrant treatment (p = 0.136). The rates of objective response and clinical benefit due to Fulvestrant were similar among patients with normal weight, overweight and obesity, respectively.CONCLUSIONS: No difference in treatment efficacy was seen between normal, overweight and obese women with metastatic HR+BC, when treated with Fulvestrant. Until further research with prospective studies is available, there is no evidence to support any modification in how Fulvestrant treatment is used in patients with metastatic breast cancer in regard to BMI.
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