| 1. |
- Boman, Caroline, et al.
(författare)
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Discordance of PD-L1 status between primary and metastatic breast cancer : A systematic review and meta-analysis
- 2021
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Ingår i: Cancer Treatment Reviews. - : Elsevier. - 0305-7372 .- 1532-1967. ; 99
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility.METHODS: Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance.RESULTS: Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001).CONCLUSION: The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
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| 2. |
- Karakatsanis, Andreas, et al.
(författare)
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Axillary evaluation in ductal cancer in situ of the breast: challenging the diagnostic accuracy of clinical practice guidelines
- 2021
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 108:9, s. 1120-1125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Staging of the axilla is not routine in ductal cancer in situ (DCIS) although invasive cancer is observed in 20-25 per cent of patients at final pathology. Upfront sentinel lymph node dissection (SLND) is advocated in clinical practice guidelines in certain situations. These include expected challenges in subsequent SLN detection and when the risk for invasion is high. Clinical practice guidelines are, however, inconsistent and lead to considerable practice variability. Methods: Clinical practice guidelines for upfront SLND in DCIS were identified and applied to patients included in the prospective SentiNot study. These patients were evaluated by six independent, blinded raters. Agreement statistics were performed to assess agreement and concordance. Receiver operating characteristic curves were constructed, to assess guideline accuracy in identifying patients with underlying invasion. Results: Eight guidelines with relevant recommendations were identified. Interobserver agreement varied greatly (kappa: 0.23-0.9) and the interpretation as to whether SLND should be performed ranged from 40-90 per cent and with varying concordance (32-88 per cent). The diagnostic accuracy was low with area under the curve ranging from 0.45 to 0.55. Fifty to 90 per cent of patients with pure DCIS would undergo unnecessary SLNB, whereas 10-50 per cent of patients with invasion were not identified as 'high risk'. Agreement across guidelines was low (kappa=0.24), meaning that different patients had a similar risk of being treated inaccurately. Conclusion: Available guidelines are inaccurate in identifying patients with DCIS who would benefit from upfront SLNB. Guideline refinement with detailed preoperative work-up and novel techniques for SLND identification could address this challenge and avoid overtreatment.
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| 3. |
- Lampropoulos, Konstantinos, et al.
(författare)
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ASCAPE : An open AI ecosystem to support the quality of life of cancer patients
- 2021
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Ingår i: 2021 IEEE 9th International Conference on Healthcare Informatics (ICHI). - : IEEE Computer Society. - 9781665401326 - 9781665429801 ; , s. 301-310
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Konferensbidrag (refereegranskat)abstract
- The latest cancer statistics indicate a decrease in cancer-related mortality. However, due to the growing and ageing population, the absolute number of people living with cancer is set to keep increasing. This paper presents ASCAPE, an open AI infrastructure that takes advantage of the recent advances in Artificial Intelligence (AI) and Machine Learning (ML) to support cancer patients' quality of life (QoL). With ASCAPE health stakeholders (e.g. hospitals) can locally process their private medical data and then share the produced knowledge (ML models) through the open AI infrastructure.
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| 4. |
- Mokhtary, Arezo, et al.
(författare)
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Mammographic Density Changes over Time and Breast Cancer Risk : A Systematic Review and Meta-Analysis
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:19
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary Although mammographic density is strongly linked to the risk of breast cancer, research on the relationship between changes in density over time and the risk of breast cancer has shown conflicting results. We found in the present meta-analysis that increased breast density over time was associated with higher breast cancer risk whereas decreased breast density might be associated with lower breast cancer risk. The results of the meta-analysis constitute a potential opportunity for more individualized screening strategies based on the evolution of breast density during mammography screening. The aim of this meta-analysis was to evaluate the association between mammographic density changes over time and the risk of breast cancer. We performed a systematic literature review based on the PubMed and ISI Web of Knowledge databases. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for cohort studies or odds ratios (ORs) and 95% confidence interval using inverse variance method. Of the nine studies included, five were cohort studies that used HR as a measurement type for their statistical analysis and four were case-control or cohort studies that used OR as a measurement type. Increased breast density over time in cohort studies was associated with higher breast cancer risk (HR: 1.61; 95% CI: 1.33-1.96) whereas decreased breast density over time was associated with lower breast cancer risk (HR: 0.78; 95% CI: 0.71-0.87). Similarly, increased breast density over time was associated with higher breast cancer risk in studies presented ORs (pooled OR: 1.85; 95% CI: 1.29-2.65). Our findings imply that an increase in breast density over time seems to be linked to an increased risk of breast cancer, whereas a decrease in breast density over time seems to be linked to a lower risk of breast cancer.
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| 5. |
- Paakkola, N.-M., et al.
(författare)
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The prognostic and predictive impact of low estrogen receptor expression in early breast cancer : a systematic review and meta-analysis
- 2021
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Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 6:6
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Traditionally, estrogen receptor (ER)-positive breast cancer has been defined as tumors with ≥1% positive for ER. The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines recommend that tumors with ER expression of 1%-10% should be classified as ER-low-positive, recognizing the limited clinical evidence on the prognostic and predictive role of low ER expression. We aimed to investigate the predictive role of ER-low expression to neoadjuvant chemotherapy (NeoCT) and the prognostic significance of ER-low expressing breast tumors compared with ER-positive or ER-negative breast tumors.METHODS: A meta-analysis was conducted using the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines and eligible articles were identified on PubMed and ISI Web of Science databases. The primary outcome was pathologic complete response and secondary outcomes were disease-free survival (DFS) and overall survival (OS). Twelve retrospective cohort studies were included in the meta-analysis. NeoCT resulted in higher pathologic complete response among patients with ER-low expression compared with ER-positive and comparable to ER-negative. Patients with ER-low breast cancer had a statistically significant worse DFS and OS compared with patients with ER-positive breast cancer, whereas no difference in DFS or OS was observed between ER-low and ER-negative subgroups.DISCUSSION: The current evidence suggests that ER-low breast cancer has a more similar outcome to ER-negative than to ER-positive breast cancer in terms of DFS and OS. ER-low expression seems also to have a predictive role regarding NeoCT. Considering the certainty of current evidence categorized as low to moderate, our results urge the need for well-designed prospective studies investigating the molecular background and the most appropriate treatment strategy for ER-low expressing breast cancer.
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| 6. |
- Schiza, Aglaia, et al.
(författare)
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Predictive role of HER2-status on the effectiveness of endocrine adjuvant treatment in postmenopausal breast cancer patients : a population-based cohort study
- 2021
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 186, s. 779-789
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: There are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade.METHODS: A population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively.RESULTS: After propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34-0.77, p value < 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41-1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14-5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10-3.38, p = 0.345).CONCLUSION: Our study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.
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| 7. |
- 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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| 8. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Improved survival without increased toxicity with influenza vaccination in cancer patients treated with checkpoint inhibitors
- 2021
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In international guidelines, influenza vaccination is recommended to cancer patients receiving antitumor treatment. Whether this recommendation should include patients treated with the recently introduced and now widely used checkpoint inhibitors (CPIs) is unclear. The immune hyperactivation after vaccination in a patient on CPI treatment may strengthen the antitumor immunity and improve patients´ prognosis. On the other hand, the hyperactivation might increase the risk for immune-related adverse events (IRAEs). Furthermore, there is a risk for decreased antitumor effect by the phenomenon of antigenic competition. Only results from few studies addressing survival have been reported and the results from studies on IRAEs are contradictory. We performed a multi-center retrospective cohort study at three Swedish centers in patients with metastatic cancer. All patients previously not treated with CPIs and who received monotherapy with a PD-1 or PD-L1 blocker between January 1st, 2016 until May 31st, 2019 were included. The most common type of malignancy was melanoma (47.8%) followed by non-small cell lung cancer (31.0%). Statistically significant longer PFS and OS were observed in multivariate analyses at 6-month landmark time in the vaccinated compared to the non-vaccinated group after adjustment for age, gender, comorbidity, performance status, CNS metastasis and line of treatment (p = .041 and 0.028, respectively). Furthermore, the incidence of any IRAE grade was comparable between vaccinated and non-vaccinated group (p = .85). In conclusion, the current study indicates that survival improves with influenza vaccination while not increasing the risk for side effects in cancer patients treated with checkpoint inhibitors. Hence, our results strongly support influenza vaccination in cancer patients receiving checkpoint inhibitors.
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| 9. |
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| 10. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Treatment patterns, risk for hospitalization and mortality in older patients with triple negative breast cancer
- 2021
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Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 12:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the treatment patterns, potential risk factors for hospitalization within one year from diagnosis, and causes of death in older patients with triple negative breast cancer (TNBC).MATERIALS AND METHODS: We performed a registry-based cohort study using the BCBaSe database which links cases of breast cancer from three Swedish healthcare regions with socioeconomic factors, hospitalizations and causes of death. Women ≥70 years old with non-metastatic TNBC, between 1/12007 and 31/122012 were included (n = 413).RESULTS: In total, 168 patients (40.7%) received chemotherapy after surgery and 123 patients (30.0%) in the whole cohort had at least one hospitalization within one year from diagnosis. The risk of hospitalization overall was increased in the group receiving chemotherapy (Odds Ratio 2.35, 95% Confidence Intervall: 1.30-4.26) mainly due to toxicities. Cumulative incidence of breast cancer mortality was comparable among different age groups (70-74 vs. 75-79 vs. ≥ 80 years old) whereas non-breast cancer mortality was higher in patients ≥80 years old. Stage at diagnosis and comorbidities were independently associated with both breast cancer-specific- and overall mortality whereas age was only associated with overall mortality.CONCLUSIONS: The use of chemotherapy in older patients with TNBC was associated with age, tumor stage, and comorbidities. Chemotherapy use was also associated with increased risk for hospitalization within one year from diagnosis. Although the impact of chemotherapy on mortality was analyzed in a multivariate manner showing neither increased or decreased mortality, no firm conclusion can be drawn due to unmeasured confounders.
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