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- Clasen, Joanna L., et al.
(author)
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Reproductive and hormonal factors and risk of renal cell carcinoma among women in the european prospective investigation into cancer and nutrition
- 2023
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In: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:14, s. 15588-15600
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Journal article (peer-reviewed)abstract
- Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
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2. |
- Huss, Linnea, et al.
(author)
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Levels of Vitamin D and Expression of the Vitamin D Receptor in Relation to Breast Cancer Risk and Survival
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 14:16
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Journal article (peer-reviewed)abstract
- Previous research suggests associations between low systemic levels of vitamin D and poor breast cancer prognosis and between expression of the vitamin D receptor (VDR) in breast cancers and survival. This study aimed to study associations between pre-diagnostic systemic levels of vitamin D and expression of VDR in subsequent breast tumors, and interactions between vitamin D and VDR on breast cancer mortality. Systemic vitamin D levels were measured in women within the Malmö Diet and Cancer Study. The expression of VDR was evaluated immunohistochemically in a tissue microarray of subsequent breast cancers. Statistical analyses followed. Women with high levels of vitamin D had a smaller proportion of VDR negative breast tumors compared to women with low levels of vitamin D (odds ratio: 0.68; 95% confidence interval: 0.41–1.13). Vitamin D levels were not found to modify the association between low VDR expression and high breast cancer mortality. To conclude, there was no statistical evidence for an association between pre-diagnostic levels of vitamin D and the expression of VDRs in breast cancer, nor did vitamin D levels influence the association between VDR expression and breast cancer mortality. Further studies are needed in order to establish the effects of vitamin D on breast cancer.
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3. |
- Huss, Linnea, et al.
(author)
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The Vitamin D Receptor as a Prognostic Marker in Breast Cancer-A Cohort Study
- 2024
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In: Nutrients. - 2072-6643. ; 16:7, s. 1-15
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Journal article (peer-reviewed)abstract
- Previous research has indicated an association between the presence of the vitamin D receptor (VDR) in breast cancer tissue and a favorable prognosis. This study aimed to further evaluate the prognostic potential of VDR located in the nuclear membrane or nucleus (liganded). The VDR protein levels were analyzed using immunohistochemistry in tumor samples from 878 breast cancer patients from Lund, Sweden, included in the Breast Cancer and Blood Study (BCBlood) from October 2002 to June 2012. The follow-up for breast cancer events and overall survival was recorded until 30 June 2019. Univariable and multivariable survival analyses were conducted, both with complete case data and with missing data imputed using multiple imputation by chained equations (MICE). Tumor-specific positive nuclear membrane VDR(num) staining was associated with favorable tumor characteristics and a longer breast cancer free interval (BCFI; HR: 0.64; 95% CI: 0.44-0.95) and overall survival (OS; HR: 0.52; 95% CI: 0.34-0.78). Further analyses indicated that VDRnum status also was predictive of overall survival when investigated in relation to ER status. There were significant interactions between VDR and invasive tumor size (Pinteraction = 0.047), as well as mode of detection (Pinteraction = 0.049). VDRnum was associated with a longer BCFI in patients with larger tumors (HR: 0.36; 95% CI: 0.14-0.93) or clinically detected tumors (HR: 0.28; 95% CI: 0.09-0.83), while no association was found for smaller tumors and screening-detected tumors. Further studies are suggested to confirm our results and to evaluate whether VDR should and could be used as a prognostic and targetable marker in breast cancer diagnostics.
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4. |
- Skarping, Ida, et al.
(author)
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Retrospective validation study of an artificial neural network-based preoperative decision-support tool for noninvasive lymph node staging (NILS) in women with primary breast cancer (ISRCTN14341750)
- 2024
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In: BMC Cancer. - 1471-2407. ; 24:1
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Journal article (peer-reviewed)abstract
- Background: Surgical sentinel lymph node biopsy (SLNB) is routinely used to reliably stage axillary lymph nodes in early breast cancer (BC). However, SLNB may be associated with postoperative arm morbidities. For most patients with BC undergoing SLNB, the findings are benign, and the procedure is currently questioned. A decision-support tool for the prediction of benign sentinel lymph nodes based on preoperatively available data has been developed using artificial neural network modelling. Methods: This was a retrospective geographical and temporal validation study of the noninvasive lymph node staging (NILS) model, based on preoperatively available data from 586 women consecutively diagnosed with primary BC at two sites. Ten preoperative clinicopathological characteristics from each patient were entered into the web-based calculator, and the probability of benign lymph nodes was predicted. The performance of the NILS model was assessed in terms of discrimination with the area under the receiver operating characteristic curve (AUC) and calibration, that is, comparison of the observed and predicted event rates of benign axillary nodal status (N0) using calibration slope and intercept. The primary endpoint was axillary nodal status (discrimination, benign [N0] vs. metastatic axillary nodal status [N+]) determined by the NILS model compared to nodal status by definitive pathology. Results: The mean age of the women in the cohort was 65 years, and most of them (93%) had luminal cancers. Approximately three-fourths of the patients had no metastases in SLNB (N0 74% and 73%, respectively). The AUC for the predicted probabilities for the whole cohort was 0.6741 (95% confidence interval: 0.6255–0.7227). More than one in four patients (n = 151, 26%) were identified as candidates for SLNB omission when applying the predefined cut-off for lymph node-negative status from the development cohort. The NILS model showed the best calibration in patients with a predicted high probability of healthy axilla. Conclusion: The performance of the NILS model was satisfactory. In approximately every fourth patient, SLNB could potentially be omitted. Considering the shift from postoperatively to preoperatively available predictors in this validation study, we have demonstrated the robustness of the NILS model. The clinical usability of the web interface will be evaluated before its clinical implementation. Trial registration: Registered in the ISRCTN registry with study ID ISRCTN14341750. Date of registration 23/11/2018.
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5. |
- Skarping, Ida, et al.
(author)
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The implementation of a noninvasive lymph node staging (NILS) preoperative prediction model is cost effective in primary breast cancer
- 2022
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 194:3, s. 577-586
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Journal article (peer-reviewed)abstract
- Purpose: The need for sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) patients is currently questioned. Our objective was to investigate the cost-effectiveness of a preoperative noninvasive lymph node staging (NILS) model (an artificial neural network model) for predicting pathological nodal status in patients with cN0 breast cancer (BC). Methods: A health-economic decision-analytic model was developed to evaluate the utility of the NILS model in reducing the proportion of cN0 patients with low predicted risk undergoing SLNB. The model used information from a national registry and published studies, and three sensitivity/specificity scenarios of the NILS model were evaluated. Subgroup analysis explored the outcomes of breast-conserving surgery (BCS) or mastectomy. The results are presented as cost (€) and quality-adjusted life years (QALYs) per 1000 patients. Results: All three scenarios of the NILS model reduced total costs (–€93,244 to –€398,941 per 1000 patients). The overall health benefit allowing for the impact of SLNB complications was a net health gain (7.0–26.9 QALYs per 1000 patients). Sensitivity analyses disregarding reduced quality of life from lymphedema showed a small loss in total health benefits (0.4–4.0 QALYs per 1000 patients) because of the reduction in total life years (0.6–6.5 life years per 1000 patients) after reduced adjuvant treatment. Subgroup analyses showed greater cost reductions and QALY gains in patients undergoing BCS. Conclusion: Implementing the NILS model to identify patients with low risk for nodal metastases was associated with substantial cost reductions and likely overall health gains, especially in patients undergoing BCS.
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6. |
- Skarping, Ida, et al.
(author)
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The NILS Study Protocol : A Retrospective Validation Study of an Artificial Neural Network Based Preoperative Decision-Making Tool for Noninvasive Lymph Node Staging in Women with Primary Breast Cancer (ISRCTN14341750)
- 2022
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In: Diagnostics. - : MDPI AG. - 2075-4418. ; 12:3
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Journal article (peer-reviewed)abstract
- Newly diagnosed breast cancer (BC) patients with clinical T1–T2 N0 disease undergo sentinel-lymph-node (SLN) biopsy, although most of them have a benign SLN. The pilot noninvasive lymph node staging (NILS) artificial neural network (ANN) model to predict nodal status was published in 2019, showing the potential to identify patients with a low risk of SLN metastasis. The aim of this study is to assess the performance measures of the model after a web-based implementation for the prediction of a healthy SLN in clinically N0 BC patients. This retrospective study was designed to validate the NILS prediction model for SLN status using preoperatively available clinicopathological and radiological data. The model results in an estimated probability of a healthy SLN for each study participant. Our primary endpoint is to report on the performance of the NILS prediction model to distinguish between healthy and metastatic SLNs (N0 vs. N+) and compare the observed and predicted event rates of benign SLNs. After validation, the prediction model may assist medical professionals and BC patients in shared decision making on omitting SLN biopsies in patients predicted to be node-negative by the NILS model. This study was prospectively registered in the ISRCTN registry (identification number: 14341750).
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