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      Assessment of the Impact of Anti-Hormonal Treatment on Bone Health in Patients With Breast Cancer Using Machine-Learning Analysis

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      https://www.riss.kr/link?id=A108641337

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      다국어 초록 (Multilingual Abstract)

      Purpose: This study analyzed the effects of anti-hormonal treatment (HTx) on bone health using real-world evidence and machine-learning analysis.Methods: We extracted 20 clinical variables and patient history of HTx by reviewing the records of 244 patients treated for breast cancer between January 2014 and June 2018 at Pusan National University Hospital. Baseline and first follow-up dual-energy absorptiometry were analyzed. To identify which of the 20 clinical variables were highly associated with the patients’ bone mineral density and trabecular bone score (TBS), we applied partial least squares discriminant analysis (PLS-DA) and MetaboAnalyst. A self-organizing map (SOM) was used to sort the patient groups based on the selected variables.Results: The patients were classified as ‘no change’ (n=161, 70.6%), ‘deteriorated’ (n=43, 18.9%), or ‘improved’ (n=24, 10.5%) according to the change in TBS during the follow-up period. The baseline TBS value was significantly lower in the improved group. The top five variables (age, HTx, duration of vitamin D and/or calcium intake, cancer stage, and body mass index) were selected using PLS-DA, which generated variable importance value (VIP) scores for all variables and high VIP scores contributed greatly to patient classification. To identify the patients’ clinical patterns using the top five selected variables, a 3×4 grid structure SOM was generated. Clusters were selected to represent the most improved, no change, and most deteriorated groups.Conclusion: This study evaluated the clinical association between HTx and bone health in patients with breast cancer under various clinical conditions and found that the characteristics of patients included in the study were too heterogeneous to be classified in clusters. Therefore, additional data should be collected for future research.
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      Purpose: This study analyzed the effects of anti-hormonal treatment (HTx) on bone health using real-world evidence and machine-learning analysis.Methods: We extracted 20 clinical variables and patient history of HTx by reviewing the records of 244 pat...

      Purpose: This study analyzed the effects of anti-hormonal treatment (HTx) on bone health using real-world evidence and machine-learning analysis.Methods: We extracted 20 clinical variables and patient history of HTx by reviewing the records of 244 patients treated for breast cancer between January 2014 and June 2018 at Pusan National University Hospital. Baseline and first follow-up dual-energy absorptiometry were analyzed. To identify which of the 20 clinical variables were highly associated with the patients’ bone mineral density and trabecular bone score (TBS), we applied partial least squares discriminant analysis (PLS-DA) and MetaboAnalyst. A self-organizing map (SOM) was used to sort the patient groups based on the selected variables.Results: The patients were classified as ‘no change’ (n=161, 70.6%), ‘deteriorated’ (n=43, 18.9%), or ‘improved’ (n=24, 10.5%) according to the change in TBS during the follow-up period. The baseline TBS value was significantly lower in the improved group. The top five variables (age, HTx, duration of vitamin D and/or calcium intake, cancer stage, and body mass index) were selected using PLS-DA, which generated variable importance value (VIP) scores for all variables and high VIP scores contributed greatly to patient classification. To identify the patients’ clinical patterns using the top five selected variables, a 3×4 grid structure SOM was generated. Clusters were selected to represent the most improved, no change, and most deteriorated groups.Conclusion: This study evaluated the clinical association between HTx and bone health in patients with breast cancer under various clinical conditions and found that the characteristics of patients included in the study were too heterogeneous to be classified in clusters. Therefore, additional data should be collected for future research.

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      참고문헌 (Reference)

      1 Rohart F, "mixOmics : an R package for ‘omics feature selection and multiple data integration" 13 : e1005752-, 2017

      2 van Buuren S, "mice : multivariate imputation by chained equations in R" 45 : 1-67, 2011

      3 Chong J, "Using MetaboAnalyst 4. 0 for metabolomics data analysis, interpretation, and integration with other omics data" 2104 : 337-360, 2020

      4 Shevroja E, "Use of trabecular bone score(TBS)as a complementary approach to dual-energy X-ray absorptiometry(DXA)for fracture risk assessment in clinical practice" 20 : 334-345, 2017

      5 Grey AB, "The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women" 99 : 636-641, 1995

      6 Vehmanen L, "Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status" 24 : 675-680, 2006

      7 Turner RT, "Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats" 122 : 1146-1150, 1988

      8 Kristensen B, "Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients : a randomized study" 12 : 992-997, 1994

      9 Francis PA, "Tailoring adjuvant endocrine therapy for premenopausal breast cancer" 379 : 122-137, 2018

      10 Lee LC, "Partial least squares-discriminant analysis(PLS-DA)for classification of high-dimensional(HD)data : a review of contemporary practice strategies and knowledge gaps" 143 : 3526-3539, 2018

      1 Rohart F, "mixOmics : an R package for ‘omics feature selection and multiple data integration" 13 : e1005752-, 2017

      2 van Buuren S, "mice : multivariate imputation by chained equations in R" 45 : 1-67, 2011

      3 Chong J, "Using MetaboAnalyst 4. 0 for metabolomics data analysis, interpretation, and integration with other omics data" 2104 : 337-360, 2020

      4 Shevroja E, "Use of trabecular bone score(TBS)as a complementary approach to dual-energy X-ray absorptiometry(DXA)for fracture risk assessment in clinical practice" 20 : 334-345, 2017

      5 Grey AB, "The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women" 99 : 636-641, 1995

      6 Vehmanen L, "Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status" 24 : 675-680, 2006

      7 Turner RT, "Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats" 122 : 1146-1150, 1988

      8 Kristensen B, "Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients : a randomized study" 12 : 992-997, 1994

      9 Francis PA, "Tailoring adjuvant endocrine therapy for premenopausal breast cancer" 379 : 122-137, 2018

      10 Lee LC, "Partial least squares-discriminant analysis(PLS-DA)for classification of high-dimensional(HD)data : a review of contemporary practice strategies and knowledge gaps" 143 : 3526-3539, 2018

      11 Savvidis C, "Obesity and bone metabolism" 17 : 205-217, 2018

      12 Carter DR, "New approaches for interpreting projected bone densitometry data" 7 : 137-145, 1992

      13 Azur MJ, "Multiple imputation by chained equations : what is it and how does it work?" 20 : 40-49, 2011

      14 Kohonen T, "Essentials of the self-organizing map" 37 : 52-65, 2013

      15 Love RR, "Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer" 326 : 852-856, 1992

      16 Zidan J, "Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer" 21 : 117-121, 2004

      17 Kalder M, "Effects of Exemestane and Tamoxifen treatment on bone texture analysis assessed by TBS in comparison with bone mineral density assessed by DXA in women with breast cancer" 17 : 66-71, 2014

      18 Lee J, "Effect of tamoxifen on the risk of osteoporosis and osteoporotic fracture in younger breast cancer survivors : a nationwide study" 10 : 366-, 2020

      19 Powles TJ, "Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women" 14 : 78-84, 1996

      20 Pothuaud L, "Correlations between grey-level variations in 2D projection images(TBS)and 3D microarchitecture : applications in the study of human trabecular bone microarchitecture" 42 : 775-787, 2008

      21 Popp AW, "Bone mineral density(BMD)and vertebral trabecular bone score(TBS)for the identification of elderly women at high risk for fracture : the SEMOF cohort study" 25 : 3432-3438, 2016

      22 Hans D, "Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density : the Manitoba study" 26 : 2762-2769, 2011

      23 Ramchand SK, "Bone health in women with breast cancer" 22 : 589-595, 2019

      24 Evans AL, "Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood" 30 : 920-928, 2015

      25 De Laet C, "Body mass index as a predictor of fracture risk : a meta-analysis" 16 : 1330-1338, 2005

      26 Early Breast Cancer Trialists’ Collaborative Group, "Aromatase inhibitors versus tamoxifen in early breast cancer : patient-level meta-analysis of the randomised trials" 386 : 1341-1352, 2015

      27 Hadji P, "Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis" 69 : 73-82, 2009

      28 Pagani O, "Adjuvant exemestane with ovarian suppression in premenopausal breast cancer" 371 : 107-118, 2014

      29 Gnant M, "Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer : 5-year follow-up of the ABCSG-12 bone-mineral density substudy" 9 : 840-849, 2008

      30 Mendez KM, "A comparative evaluation of the generalised predictive ability of eight machine learning algorithms across ten clinical metabolomics data sets for binary classification" 15 : 150-, 2019

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