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  • Anorexia Nervosa with Markedly High Bone Turnover and Hyperphosphatemia During Refeeding Rectified by Denosumab
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-23
    M. T. Kilbane, R. K. Crowley, P. J. Twomey, C. Maher, M. J. McKenna

    Abstract We describe a unique case of hyperphosphatemia associated with a very high bone turnover rate in a 51-year-old postmenopausal woman with undiagnosed anorexia nervosa (AN) who presented with a low-trauma hip fracture. In view of her severely malnourished state, she was not fit for surgery. She was treated according to a refeeding protocol that mandated bed rest. Contrary to expectation, she developed sustained hyperphosphatemia and borderline hypercalcemia. Bone remodelling markers, both resorption and formation, were markedly elevated. Parathyroid hormone (PTH) was low-normal at 1.7 pmol/L, C-terminal fibroblast growth factor 23 (FGF23) was high at 293 RU/ml, but tubular maximum reabsorption of phosphate (TmPO4/GFR) was elevated at 1.93 mmol/L. Denosumab 60 mg was administered that was followed by: rapid normalisation of serum phosphate; normalisation of resorption markers, transient hypocalcaemia with secondary hyperparathyroidism, and normalisation of both TmPO4/GFR and C-terminal FGF23. We speculate that prolonged immobilization as part of AN management led to a high remodelling state followed by hyperphosphatemia and high-normal calcium with appropriate suppression of PTH and that marked hyperphosphatemia and high TmP/GFR despite high FGF23 indicates the necessity of PTH adequacy for excess FGF23 to lower TmP/GFR.

    更新日期:2020-01-24
  • Harmonization of commercial assays for PINP; the way forward
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-23
    S. D. Vasikaran, H. P. Bhattoa, R. Eastell, A. C. Heijboer, N. R. Jørgensen, K. Makris, C. Ulmer, J. A. Kanis, C. Cooper, S. Silverman, E. Cavalier

    Abstract Summary International Federation of Clinical Chemistry and Laboratory Medicine and The International Osteoporosis Foundation Joint Committee on Bone Metabolism believes that the harmonization of PINP assays is an achievable and practical goal. Introduction In order to examine the agreement between current commercial assays, a multi-center study was performed for PINP in serum and plasma. Methods The automated methods for PINP (Roche Cobas and IDS iSYS) gave similar results. A significant proportional bias was observed between the two automated assays and the Orion radioimmunoassay (RIA) for PINP. Results Results from other published studies comparing PINP values among these three assays broadly support our findings. Taken together, these results confirm that harmonized PINP measurements exist between the two automated assays (Roche Cobas and IDS iSYS) when the eGFR is > 30 mL/min/1.73m2, but a significant bias exists between the Orion RIA and the two automated assays. Conclusion Therefore, in subjects with normal renal function, PINP results reported by the Roche Cobas and IDS iSYS assays are similar and may be used interchangeably, and similar reference intervals and treatment targets could be applied for the two automated assays. Harmonization between the automated assays and the RIA is potentially possible with the use of common calibrators and the development of a reference method for PINP. This should also help ensure that any new commercial assay developed in the future will attain similar results. IOF and IFCC are committed to working together towards this goal with the cooperation of the reagent manufacturing industry.

    更新日期:2020-01-23
  • Correction to: Weaker bones and white skin as adaptions to improve anthropological “fitness” for northern environments
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-22
    R. Vieth

    The original version of this article, published on 06 November 2019 unfortunately contained a mistake.

    更新日期:2020-01-23
  • Accelerometer-based prediction of skeletal mechanical loading during walking in normal weight to severely obese subjects
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-21
    L. Veras, F. Diniz-Sousa, G. Boppre, V. Devezas, H. Santos-Sousa, J. Preto, J. P. Vilas-Boas, L. Machado, J. Oliveira, H. Fonseca

    Abstract Summary There is no objective way to monitor mechanical loading characteristics during exercise for bone health improvement. We developed accelerometry-based equations to predict ground reaction force (GRF) and loading rate (LR) in normal weight to severely obese subjects. Equations developed had a high and moderate accuracy for GRF and LR prediction, respectively, thereby representing an accessible way to determine mechanical loading characteristics in clinical settings. Introduction There is no way to objectively prescribe and monitor exercise for bone health improvement in obese patients based on mechanical loading characteristics. We aimed to develop accelerometry-based equations to predict peak ground reaction forces (pGRFs) and peak loading rate (pLR) on normal weight to severely obese subjects. Methods Sixty-four subjects (45 females; 84.6 ± 21.7 kg) walked at different speeds (2–6 km·h−1) on a force plate–equipped treadmill while wearing accelerometers at lower back and hip. Regression equations were developed to predict pGRF and pLR from accelerometry data. Leave-one-out cross-validation was used to calculate prediction accuracy and Bland–Altman plots. Actual and predicted values at different speeds were compared by repeated measures ANOVA. Results Body mass and peak acceleration were included for pGRF prediction and body mass and peak acceleration transient rate for pLR prediction. All pGRF equation coefficients of determination were above 0.89, a good agreement between actual and predicted pGRFs, with a mean absolute percent error (MAPE) below 6.7%. No significant differences were observed between actual and predicted pGRFs at each walking speed. Accuracy indices from our equations were better than previously developed equations for normal weight subjects, namely a MAPE approximately 3 times smaller. All pLR prediction equations presented a lower accuracy compared to those developed to predict pGRF. Conclusion Walking pGRF and pLR in normal weight to severely obese subjects can be predicted with moderate to high accuracy by accelerometry-based equations, representing an easy and accessible way to determine mechanical loading characteristics in clinical settings.

    更新日期:2020-01-22
  • Magnesium oxide and hip fracture in the elderly: a population-based retrospective cohort analysis
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-21
    Y.Y. Wu, C.L. Chang, J.H. Wang, W.T. Wei

    Abstract Summary Using national insurance claims of Taiwan, we found that magnesium oxide (MgO) use is associated with an increased risk of hip fracture in the elderly. Further studies are warranted to explore the mechanisms associated with MgO use that lead to hip fracture. Purpose The purpose of this study was to investigate the association between MgO use and hip fracture risk in the elderly (age > 65 years). Methods This nationwide population-based retrospective study was conducted from 1996 to 2013. Individuals with (n = 26,069) and without (n = 26,069) MgO use were enrolled after propensity score matching. Primary outcome was a hip fracture. After adjusting for age, sex, comorbidities, and medications, multivariate Cox proportional hazards regression models were used to calculate incidences and risk of hip fracture [hazard ratio (HR)]. Results During the mean follow-up duration of 4.8 years in the MgO cohort and 5.7 years in the non-MgO cohort, respectively 1547 and 1107 cases developed a hip fracture. MgO use was identified as a risk factor for hip fracture in both univariate [crude HR, 1.68; 95% confidence interval (CI), 1.55–1.81; p < 0.001] and multivariate [adjusted HR (aHR), 1.66; 95% CI, 1.54–1.80; p < 0.001] Cox proportional hazards regression models. The cumulative incidence of hip fracture was significantly higher in the MgO cohort than in the non-MgO cohort (1.23 per 100 person-years vs. 0.74 per 100 person-years, logrank test, p < 0.001). Conclusion MgO use is an independent risk factor for hip fracture in the elderly.

    更新日期:2020-01-21
  • Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-20
    C. I. Condurache, S. Chiu, P. Chotiyarnwong, H. Johansson, L. Shepstone, E. Lenaghan, C. Cooper, S. Clarke, R. F. S. Khioe, R. Fordham, N. Gittoes, I. Harvey, N. C. Harvey, A. Heawood, R. Holland, A. Howe, J. A. Kanis, T. Marshall, T. W. O’Neill, T. J. Peters, N. M. Redmond, D. Torgerson, D. Turner, E. McCloskey

    Abstract Summary A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. Introduction To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. Methods The SCOOP study recruited 12,483 women aged 70–85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. Results Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55–0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1–2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. Conclusion Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.

    更新日期:2020-01-21
  • Comparison of bone structure and microstructure in the metacarpal heads between patients with psoriatic arthritis and healthy controls: an HR-pQCT study
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-14
    D. Wu, J.F. Griffith, S.H.M. Lam, P. Wong, J. Yue, L. Shi, E.K. Li, I.T. Cheng, T.K. Li, V.W. Hung, L. Qin, L.-S. Tam

    Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH.

    更新日期:2020-01-15
  • Effect of vitamin D on bone strength in older African Americans: a randomized controlled trial
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-14
    R. Dhaliwal, S. Islam, M. Mikhail, L. Ragolia, J.F. Aloia

    There is controversy over whether African Americans have higher vitamin D requirements than recommended by the Institute of Medicine. We previously reported that maintaining serum 25(OH)D above 30 ng/mL does not prevent age-related bone loss. Herein, we report that bone strength is also unaffected by maintaining this level in this population.

    更新日期:2020-01-14
  • Incidental bilateral calcaneal fractures following overground walking with a wearable robotic exoskeleton in a wheelchair user with a chronic spinal cord injury: is zero risk possible?
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-13
    A. Bass, S.N. Morin, M. Vermette, M. Aubertin-Leheudre, D.H. Gagnon

    Abstract Many individuals with spinal cord injury (SCI) rely on wheelchairs as their primary mode of locomotion leading to reduced weight-bearing on the lower extremities, which contributes to severe bone loss and increased risk of fragility fractures. Engaging in a walking program may reverse this vicious cycle, as this promotes lower extremity weight-bearing and mobility, which may reduce bone loss and fragility fracture risk. However, fragility fracture risk associated with the use of wearable robotic exoskeletons (WREs) in individuals with SCI needs consideration. A 35-year-old man with chronic complete sensorimotor SCI (neurological level = T6) and low initial bone mineral density enrolled in a 6- to 8-week WRE-assisted walking program after successfully completing an initial clinical screening process and two familiarization sessions with the WRE. However, after the first training session with the WRE, he developed bilateral localized ankle edema. Training was suspended, and a CT-scan revealed bilateral calcaneal fractures, which healed with conservative treatment over a 12-week period. Opportunities for improving clinical screening and WRE design are explored. The relevance of developing clinical practice guidelines for safe initiation and progression of intensity during WRE-assisted walking programs is highlighted. This case of bilateral calcaneal fractures illustrates that aiming for “zero risk” during WRE-assisted walking programs may not be realistic. Although WREs are a relatively new technology, current evidence confirms their potential to greatly improve health and quality of life in individuals with chronic SCI. Hence, ensuring their safe use remains a key priority.

    更新日期:2020-01-14
  • Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-13
    H.P. Bögl, K. Michaëlsson, G. Zdolsek, J. Höijer, J. Schilcher

    Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type.

    更新日期:2020-01-14
  • Correction to: Impact of whole dairy matrix on musculoskeletal health and aging–current knowledge and research gaps
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-13
    N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli, Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup

    The article Impact of whole dairy matrix on musculoskeletal health and aging–current knowledge and research gaps written by N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli,Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup.

    更新日期:2020-01-13
  • Incidence of distal radius fracture in a general population in southern Sweden in 2016 compared with 2001
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-13
    M. Ali, A. Eiriksdottir, M. Murtadha, A. Åkesson, I. Atroshi

    In this population-based study, we compared the incidence of distal radius fracture in 2016 with that in the same region’s adult general population in 2001 using radiographs to identify fracture cases. We showed that the incidence decreased by 24% in 2016 compared with 2001 indicating an important development.

    更新日期:2020-01-13
  • Adherence to fracture liaison service programs in patients over 70: the hidden part of the iceberg
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-11
    B. Mugnier, A. Daumas, S. Doddoli, S. Belmeliani, A.-L. Couderc, B. Mizzi, P. Lévêque, P. Villani

    Abstract Summary Significant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence. Introduction FLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70. Methods Our multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program. Results About half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned. Conclusion We observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

    更新日期:2020-01-13
  • Bone microstructure and volumetric bone mineral density in patients with hyperuricemia with and without psoriasis
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-10
    D. Simon, J. Haschka, C. Muschitz, A. Kocijan, A. Baierl, A. Kleyer, G. Schett, S. Kapiotis, H. Resch, M. Sticherling, J. Rech, R. Kocijan

    We analyzed volumetric bone mineral density (vBMD) and bone microstructure using HR-pQCT in subjects with normouricemia (NU) and subjects with hyperuricemia (HU) with and without psoriasis (PSO). HU was associated with higher cortical vBMD and thickness. Differences in average and trabecular vBMD were found between patients with PSO + HU and NU.

    更新日期:2020-01-11
  • Effects of a resistance and balance exercise programme on physical fitness, health-related quality of life and fear of falling in older women with osteoporosis and vertebral fracture: a randomized controlled trial
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-10
    B. Stanghelle, H. Bentzen, L. Giangregorio, A.H. Pripp, D. Skelton, A. Bergland

    Abstract Summary Exercise is recommended for people with osteoporosis, but the effect for people who have suffered vertebral fracture is uncertain. This study shows that a multicomponent exercise-program based on recommendations for people with osteoporosis improved muscle strength, balance, and fear of falling in older women with osteoporosis and vertebral fracture. Introduction Guidelines for exercise strongly recommend that older adults with osteoporosis or osteoporotic vertebral fracture should engage in a multicomponent exercise programme that includes resistance training in combination with balance training. Prior research is scarce and shows inconsistent findings. This study examines whether current exercise guidelines for osteoporosis, when applied to individuals with vertebral fractures, can improve health outcomes. Methods This single blinded randomized controlled trial included 149 older women diagnosed with osteoporosis and vertebral fracture, 65+ years. The intervention group performed a 12-week multicomponent exercise programme, the control group received usual care. Primary outcome was habitual walking speed, secondary outcomes were physical fitness (Senior Fitness Test, Functional Reach and Four Square Step Test), health-related quality of life and fear of falling. Descriptive data was reported as mean (standard deviation) and count (percent). Data were analyzed following intention to treat principle and per protocol. Between-group differences were assessed using linear regression models (ANCOVA analysis). Results No statistically significant difference between the groups were found on the primary outcome, walking speed (mean difference 0.04 m/s, 95% CI − 0.01–0.09, p = 0.132). Statistically significant between-group differences in favour of intervention were found on FSST (dynamic balance) (mean difference − 0.80 s, 95% CI − 1.57 to − 0.02, p = 0.044), arm curl (mean difference 1.55, 95% CI 0.49–2.61, p = 0.005) and 30-s STS (mean difference 1.85, 95% CI 1.04–2.67, p < 0.001), as well as fear of falling (mean difference − 1.45, 95% CI − 2.64 to − 0.26, p = 0.018). No statistically significant differences between the groups were found on health-related quality of life. Conclusion Twelve weeks of a supervised multicomponent resistance and balance exercise programme improves muscle strength and balance and reduces fear of falling, in women with osteoporosis and a history of vertebral fractures. Trial registration ClincialTrials.gov Identifier: NCT02781974. Registered 25.05.16. Retrospectively registered.

    更新日期:2020-01-11
  • Low volumetric bone density is a risk factor for early complications after spine fusion surgery
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-09
    Y. Liu, A. Dash, A. Krez, H. J. Kim, M. Cunningham, F. Schwab, A. Hughes, B. Carlson, A. Samuel, E. Marty, H. Moore, D. J. McMahon, J. A. Carrino, R. S. Bockman, E. M. Stein

    This study aims to investigate lumbar spine (LS) volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion.

    更新日期:2020-01-09
  • No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-04
    E.D. Alten, A. Chaturvedi, M. Cullimore, A.A. Fallon, L. Habben, I. Hughes, N.T. O’Malley, H. Rahimi, D. Renodin-Mead, B.L. Schmidt, G.A. Weinberg, D.R. Weber

    Scurvy, due to vitamin C deficiency, is commonly referenced as a “forgotten” or “historical” disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases.

    更新日期:2020-01-04
  • Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-03
    H. McKee, G. Ioannidis, A. Lau, D. Treleaven, A. Gangji, C. Ribic, M. W. Pack, A. Papaioannou, J. D. Adachi

    Abstract Summary A retrospective chart review was conducted on 85 renal transplant patients aged 19–88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; at years 1, 2, and 3; and at final follow-up (average of 3.4 years). Both bisphosphonate and denosumab treatments increased lumbar spine bone density; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Denosumab treatment increased femoral neck BMD, whereas bisphosphonate treatment had a mean decrease in femoral neck BMD at final follow-up. Thus, our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant. Introduction To compare the clinical effectiveness and safety between the use of denosumab and bisphosphonates on bone density and incidence of adverse events in renal transplant patients. Methods A retrospective chart review was conducted on 85 renal transplant patients aged 19–88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; years 1, 2, and 3; and at final follow-up (average of 3.4 years). Results Absolute change in lumbar spine and femoral neck BMD over the treatment period was 0.029 ± 0.075 g/cm2 and − 0.003 ± 0.064 g/cm2, respectively, in the bisphosphonate group. Absolute change in lumbar spine and femoral neck BMD at final follow-up was 0.072 ± 0.094 g/cm2 and 0.025 ± 0.063 g/cm2, respectively, in the denosumab group. Denosumab resulted in significantly greater increases in lumbar spine BMD (0.045 g/cm2 greater in the denosumab group). Similarly, the absolute change in BMD at the femoral neck was 0.022 g/cm2 greater in the denosumab group as compared with the bisphosphonate group. The denosumab group had one event of severe hypocalcemia following first injection and one report of hospitalized pneumonia. No serious adverse events were reported in the bisphosphonate group. Conclusions Both treatments increased lumbar spine BMD; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant.

    更新日期:2020-01-04
  • Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-03
    M. L. Bouxsein, P. Zysset, C. C. Glüer, M. McClung, E. Biver, D.D. Pierroz, S. L. Ferrari, on behalf of the IOF Working Group on Hip Bone Strength as a Therapeutic Target

    We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment.

    更新日期:2020-01-04
  • How does women’s bone health recover after lactation? A systematic review and meta-analysis
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-02
    F. M. F. Grizzo, A. C. J. Alarcão, C. M. Dell’ Agnolo, R. B. Pedroso, T. S. Santos, J. R. N. Vissoci, M. M. Pinheiro, M. D. B. Carvalho, S. M. Pelloso

    This is a systematic review aiming to evaluate the recovery of bone mass after lactation-related loss. Bone loss is transitory with recovery depending on the return of menstruation and weaning, and several compensatory homeostatic mechanisms are involved to minimize any significant damage to the maternal skeleton.

    更新日期:2020-01-04
  • An 11-year review of hip fracture hospitalisations, health outcomes, and predictors of access to in-hospital rehabilitation for adults ≥ 65 years living with and without dementia: a population-based cohort study
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-02
    R. Mitchell, B. Draper, H. Brodaty, J. Close, H.P. Ting, R. Lystad, I. Harris, L. Harvey, C. Sherrington, I.D. Cameron, J. Braithwaite

    Abstract Summary This study examined hip fracture hospitalisation trends and predictors of access to rehabilitation for adults aged ≥ 65 years living with and without dementia. The hospitalisation rate was 2.5 times higher for adults living with dementia and adults who lived in aged care were between 4.8 and 9.3 times less likely to receive rehabilitation. Introduction To examine hip fracture hospitalisation temporal trends, health outcomes, and predictors of access to in-hospital rehabilitation for older adults living with and without dementia. Methods A population-based retrospective cohort study of adults aged ≥ 65 years hospitalised with a hip fracture during 2007–2017 in New South Wales, Australia. Results Of the 69,370 hip fracture hospitalisations, 27.1% were adults living with dementia. The hip fracture hospitalisation rate was 2.5 times higher for adults living with dementia compared with adults with no dementia (1186.6 vs 492.9 per 100,000 population). The rate declined by 6.1% per year (95%CI − 6.6 to − 5.5) for adults living with dementia and increased by 1.0% per year (95%CI 0.5–1.5) for adults with no dementia. Multivariable associations identified that adults living with dementia who experienced high frailty and increasing age were between 1.6 and 1.8 times less likely to receive in-hospital rehabilitation. Adults who were living in long-term aged care facilities were between 4.8 and 9.3 times less likely to receive in-hospital rehabilitation which varied by the presence of dementia or delirium. Conclusion Consistent criteria should be applied to determine rehabilitation access, and rehabilitation services designed for older adults living with dementia or in aged care are needed. Highlights • Adults living with dementia were able to make functional gains following hip fracture rehabilitation. • Need to determine consistent criteria to determine access to hip fracture rehabilitation. • Rehabilitation services specifically designed for adults living with dementia or in aged care are needed.

    更新日期:2020-01-04
  • Real-world impact of glucocorticoid replacement therapy on bone mineral density: retrospective experience of a large single-center CAH cohort spanning 24 years
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2020-01-02
    L. L. Iervolino, B. Ferraz-de-Souza, R. M. Martin, F. C. Costa, M. C. Miranda, B. B. Mendonça, T. S. Bachega

    The congenital adrenal hyperplasia population seems to have an intrinsic tendency to a high frequency of low bone mass. However in this single-center and long-term evaluated cohort, the simplified corticoid regimen, with exclusive dexamethasone single dose reposition during adulthood, did not represent a risk factor for decrease in bone health.

    更新日期:2020-01-04
  • Higher fracture prevalence and smaller bone size in patients with hEDS/HSD—a prospective cohort study
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-24
    T. Banica, M. Coussens, C. Verroken, P. Calders, I. De Wandele, F. Malfait, H.-G. Zmierczak, S. Goemaere, B. Lapauw, L. Rombaut

    Abstract Summary Increased fracture risk in patients with Ehlers-Danlos syndromes has been reported, but the reasons for it are incompletely understood. We aimed to investigate possible determinants of this increased risk and found that hEDS/HSD patients present with a cortical bone size deficit compared with control subjects, possibly related to lower mechanical loading. Introduction The Ehlers-Danlos syndromes (EDS) comprise a group of heritable connective tissue disorders caused by defects in the biosynthesis, secretion, and/or organization of fibrillar collagens which might impair bone strength. Our aim was to compare fracture prevalence, volumetric and areal bone mineral density (BMD), bone geometry, muscle size and the muscle-bone interaction, body composition and longitudinal changes therein between patients with hypermobile EDS (hEDS) or hypermobility spectrum disorder (HSD), and healthy control subjects. Methods Cross-sectional data comprised 39 female hEDS/HSD patients (age 41 ± 11 years) and 43 age-matched controls. After 8 years, 27 hEDS/HSD and 17 control subjects were re-evaluated. Tibial trabecular and cortical volumetric BMD, bone mineral content (BMC), cortical bone geometry, and lower leg muscle cross-sectional area (CSA) were measured using pQCT. Body composition, areal BMD, and BMC were determined by DXA. Results At baseline, patients with hEDS/HSD presented with a smaller cortical bone area, smaller cortical thickness and muscle CSA, and a higher fracture prevalence than control subjects (all p < 0.05). No differences in areal or volumetric BMD were found. Longitudinally, muscle CSA decreased in both groups and muscle density decreased in the hEDS/HSD group (p < 0.001) whereas all bone parameters remained unchanged. Conclusion hEDS/HSD patients have a cortical bone size deficit compared with controls, possibly contributing to their increased fracture risk. They presented with decreased muscle CSA but normal bone/muscle area ratio, suggesting that this bone size deficit is likely secondary to decreased mechanical loading. Further, there were no arguments for accelerated bone loss in hEDS/HSD subjects.

    更新日期:2020-01-04
  • Modification of the RANKL-RANK-binding site for the immunotherapeutic treatment of osteoporosis
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-20
    Y. Ko, G. Lee, B. Kim, M. Park, Y. Jang, W. Lim

    Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment.

    更新日期:2020-01-04
  • A fall in the previous 12 months predicts fracture in the subsequent 5 years in postmenopausal women
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-19
    N. Afrin, R. Sund, R. Honkanen, H. Koivumaa-Honkanen, T. Rikkonen, L. Williams, H. Kröger

    The purpose of this study was to evaluate if a history of falls predicts future postmenopausal fractures and if this prediction variesaccording to frequency, mechanism, and severity of falls and site of fractures.

    更新日期:2020-01-04
  • Management of Paget’s disease of bone
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-17
    I.R. Reid

    Paget’s disease is a progressive focal bone condition which can result in pain, low quality of life, deformity and other complications. Disease progression can be halted with potent bisphosphonates, resulting in improvement in both quality of life and pain, and normalisation of scintigraphy, plain radiographs and bone histology. Zoledronate has transformed the treatment of Paget’s disease, producing sustained remissions in almost all patients. Thus, it is now possible to normalise bone cell activity and prevent disease progression at low cost, with one or two intravenous injections of zoledronate, greatly reducing follow-up costs. Patients with Paget’s disease who are symptomatic or at risk of complications should have the opportunity to reap these therapeutic benefits.

    更新日期:2020-01-04
  • Postmenopausal women with osteoporosis consume high amounts of vegetables but insufficient dairy products and calcium to benefit from their virtues: the CoLaus/OsteoLaus cohort
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-17
    A. Lanyan, P. Marques-Vidal, E. Gonzalez-Rodriguez, D. Hans, O. Lamy

    Abstract Summary We evaluated the associations between nutrients, dietary patterns or compliance to dietary guidelines and bone health among postmenopausal women from the CoLaus/OsteoLaus cohort. Postmenopausal women with osteoporosis consume a high amount of vegetables but insufficient amount of dairy products and calcium to benefit from their adherence to dietary guidelines. Introduction Diet plays a significant role in the prevention of osteoporosis (OP). We evaluated the associations between nutrients, dietary patterns or compliance (expressed in odds of meeting) to dietary Swiss guidelines and bone health (T score < − 2.5 SD, TBS < 1230) among postmenopausal women. Methods One thousand two hundred fifteen women (64.3 ± 7.5 years) from the CoLaus/OsteoLaus cohort (Lausanne, Switzerland) had their dietary intake assessed using a validated food frequency questionnaire. Bone mineral density (BMD), trabecular bone score (TBS) and vertebral fractures were evaluated with DXA. OP risk factors, calcium supplements (> 500 mg) and prevalent major OP fractures were assessed by questionnaire. Results One hundred eighty of 1195 women had OP according to BMD, 87/1185 a low TBS and 141/1215 prevalent major OP fractures. In multivariate analysis (adjusted for total energy intake, age, antiosteoporotic treatment, educational level, BMI, sedentary status and diabetes), OP women consumed more vegetable proteins (21.3 ± 0.4 vs 19.6 ± 0.2 g/day), more fibres (18.2 ± 0.5 vs 16.5 ± 0.2 g/day), less animal proteins (40.0 ± 1.1 vs 42.8 ± 0.4 g/day), less calcium (928 ± 30 vs 1010 ± 12 mg/day) and less dairy products (175 ± 12 vs 215 ± 5 g/day), all p ≤ 0.02. According to guidelines, OP women had a tendency to higher compliance for vegetables (OR (95% CI) 1.50 (0.99–2.26)) and a lower compliance for dairy (OR (95% CI) 0.44 (0.22–0.86)) than those without OP. Women taking calcium supplements consumed significantly higher amounts of dairy products. No association was found between TBS values or prevalent OP fractures and any dietary components. Conclusion Postmenopausal women with OP consume a high amount of vegetables but insufficient amount of dairy products and calcium. TBS does not seem to be influenced by diet.

    更新日期:2020-01-04
  • Comparison of multimedia and printed patient education tools for patients with osteoporosis: a 6-month randomized controlled trial
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-16
    M.A. Lopez-Olivo, J.K.A. des Bordes, H. Lin, T. Rizvi, R.J. Volk, M.E. Suarez-Almazor

    Abstract Summary We conducted a randomized controlled trial to compare the efficacy of adding a video tool to a printed booklet on osteoporosis. Both strategies were effective in increasing knowledge and decreasing decisional conflict. There was no difference in the measured outcomes between the intervention and control groups. Patient preferences and learning styles are key factors in deciding a presentation format when educating patients with osteoporosis. Introduction Innovative approaches to patient education about self-management in osteoporosis may improve outcomes. Methods We conducted a randomized controlled trial to compare the efficacy of adding a multimedia patient education tool involving video modeling to a printed educational booklet on osteoporosis. Participants were post-menopausal women with osteoporosis. We assessed osteoporosis knowledge, decisional conflict, self-efficacy, and effectiveness in disease management at baseline, immediately post-intervention, and at 3 and 6 months. Linear regression models were used to explore changes in outcomes at 6 months with respect to baseline characteristics. Results Two hundred and twenty-five women were randomized, 111 to receive the multimedia tool in addition to the booklet and 114 to receive the booklet alone. Knowledge and decisional conflict scores significantly improved in both groups at all post-intervention assessment points, but with no significant differences in score changes between the groups. Self-efficacy and disease management effectiveness showed no significant changes from baseline. In the entire cohort, younger age was associated with better effectiveness in disease management and Hispanic women had greater gains in knowledge at 6 months compared to White women. Women with limited health literacy who had received the multimedia tool in addition to the printed materials had higher decisional conflict than those who received printed materials alone. Conclusion Both multimedia and printed tools increased knowledge and decreased decisional conflict to the same extent, neither of the educational materials proved to be better than the other. For women with limited health literacy, receiving the booklet alone was more effective in reducing decisional conflict after 6 months, than adding the multimedia tool.

    更新日期:2020-01-04
  • Fracture prevention by screening for high fracture risk: a systematic review and meta-analysis
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-14
    T. Merlijn, K.M.A. Swart, H.E. van der Horst, J.C. Netelenbos, P.J.M. Elders

    This systematic review and meta-analysis showed a significant reduction of (major) osteoporotic fractures and hip fractures after screening using fracture risk assessment and bone densitometry compared with usual care. The results indicate that screening is effective for fracture risk reduction, especially hip fractures. To perform a systematic review and meta-analysis of population screening for high fracture risk on fracture prevention compared with usual care. MEDLINE and Embase were searched for studies published until June 20th 2019. Randomized studies were selected that screened for high fracture risk using at least bone densitometry, screened in a general population, provided subsequent treatment with anti-osteoporosis medication, had a usual care group as comparator, and had at least one fracture-related outcome (all fractures, (major) osteoporotic fractures, or hip fractures). The primary assessment was the hazard ratio (HR) for fracture-related outcomes. All-cause mortality was a secondary outcome. Random-effects models were used to estimate pooled HRs. We identified 1186 potentially eligible articles and included three randomized studies: the ROSE study, the SCOOP study, and the SOS with a total number of N = 42,009 participants. Respectively, 11%, 15%, and 18% of the participants in the intervention group started medication. Meta-analysis showed a statistically significant and clinically relevant reduction of osteoporotic fractures (HR = 0.95, 95% confidence interval (CI) = 0.89–1.00), major osteoporotic fractures (HR = 0.91; 95%CI = 0.84–0.98), and hip fractures (HR = 0.80; 95%CI = 0.71–0.91), but no reduction of all fractures (HR = 0.95; 95%CI = 0.89–1.02). The pooled HR for the secondary outcome all-cause mortality was 1.04 (95% CI = 0.95–1.14). Numbers needed to screen to prevent one fracture were 247 and 272 for osteoporotic fractures and hip fractures, respectively (corresponding to 113 and 124 performed bone densitometry examinations, and 25 and 28 persons being treated). This meta-analysis showed that population screening is effective to reduce osteoporotic fractures and hip fractures. Implementation of screening in older women should be considered as serious option to prevent osteoporotic fractures, especially hip fractures.

    更新日期:2020-01-04
  • Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-14
    G. Tsvetov, O. Amitai, T. Shochat, I. Shimon, A. Akirov, T. Diker-Cohen

    Abstract Summary Hypocalcemia was reported at low rates (0.05–1.7%) in denosumab-treated postmenopausal women with osteoporosis. This real-life study shows a 7.4% rate of denosumab-induced hypocalcemia in community-dwelling osteoporotic men and women. Pretreatment serum calcium and creatinine levels are major predictors for this complication. Serum-calcium monitoring may help to identify and prevent severe hypocalcemia. Purpose RCTs have reported a 0.05–1.7% rate of hypocalcemia in denosumab-treated postmenopausal women with osteoporosis, but long-term real-life data are lacking. We assessed the rate of hypocalcemia in osteoporotic community-dwelling patients treated with denosumab. Methods A retrospective analysis was conducted based on medical records (2010–2018) from a large HMO. An albumin-adjusted serum calcium concentration lower than 8.5 mg/dL was defined as hypocalcemia. Results We included 2005 patients (93% women, mean age 76 ± 9 years). Hypocalcemia developed during treatment in 149 patients (7.4%; 1% less than 8 mg/dL): in 66 after 0.5–1 years; 48 after 1–2 years; 35 after > 2 years. On comparison of the hypocalcemic and normocalcemic patients, the strongest predictors of hypocalcemia were pretreatment levels of albumin-adjusted serum calcium (9.1 ± 0.4 vs. 9.4 ± 0.5 mg/dL, respectively; p < 0.05) and creatinine (0.9 ± 0.5 vs. 0.8 ± 0.3 mg/dL, respectively; p < 0.05). The hypocalcemia rate increased in parallel to a decrease in eGFR (p = 0.032 for the difference between eGFR ranges). Baseline calcium level ≤ 9.31 mg/dL predicted hypocalcemia with a sensitivity of 77% and specificity of 56%. A model of (− 2)*calcium + creatinine predicted hypocalcemia (3.7% when lower and 17.1% when higher than − 17.4). Gender, age, 25-hydroxyvitamin-D, parathyroid hormone, alkaline phosphatase, and whether denosumab was given as first or advanced line of osteoporotic therapy had no predictive value. Conclusion Real-life rates of denosumab-induced hypocalcemia are higher than previously reported. Hypocalcemia might develop after each dose of denosumab in ongoing treatment. Adequate calcium and vitamin D supplementation are needed. Serum calcium monitoring is advised in high-risk patients for early detection of severe hypocalcemia.

    更新日期:2020-01-04
  • Diabetes and fractures: new evidence of atypical femoral fractures?
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-14
    N.H. Rasmussen, J. Dal, F. de Vries, J.P. van den Bergh, M.H. Jensen, P. Vestergaard

    Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures.

    更新日期:2020-01-04
  • Patient engagement in clinical guidelines development: input from > 1000 members of the Canadian Osteoporosis Patient Network
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-14
    S. N. Morin, M. Djekic-Ivankovic, L. Funnell, L. Giangregorio, I. B. Rodrigues, R. Ridout, S. Feldman, S. Kim, H. McDonald-Blumer, G. Kline, W. E. Ward, N. Santesso, W. D. Leslie

    Patient engagement in clinical guidelines development is essential. The results of a self-administered online survey identified themes important to people living with osteoporosis and will inform the development of Osteoporosis Canada clinical guidelines recommendations.

    更新日期:2020-01-04
  • Increased risk for hip fracture after death of a spouse—further support for bereavement frailty?
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-12
    C. H. Vala, M. Lorentzon, V. Sundh, H. Johansson, C. Lewerin, S. Sten, M. Karlsson, C. Ohlsson, B. Johansson, J. A. Kanis, D. Mellström

    Death of a spouse is associated with poorer physical and mental health. We followed all married individuals, born from 1902 to 1942, during the period from 1987 to 2002, and found that widows and widowers had higher risk for hip fracture, compared with still married women and men.

    更新日期:2020-01-04
  • Risk for hip fracture before and after total knee replacement in Sweden
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-12
    C.H. Vala, J. Kärrholm, J.A. Kanis, H. Johansson, S. Sten, V. Sundh, M. Karlsson, M. Lorentzon, D. Mellström

    Abstract Summary We studied the risk for hip fracture before and after total knee replacement (TKR) in the entire population in Sweden. Women and men had a low risk for hip fracture before TKR but an increased risk the first year after TKR. Purpose It is known that osteoarthritis is associated with high bone mass. We therefore studied the risk of hip fracture before and after total knee replacement (TKR), risk of different hip fracture types, and risk subdivided in genders and age groups. Methods We followed the total Swedish population born between 1902 and 1952 (n = 4,258,934) during the period 1987–2002 and identified all patients with TKR due to primary OA (n = 39,291), and all patients with hip fracture (n = 195,860) in the Swedish National Inpatient Register. The risk time analyses were based on Poisson regression models. Results The hazard ratio (HR) for hip fracture the last year before TKR was 0.86 (95% CI 0.74 to 1.00) and the first year after 1.26 (95% CI 1.11 to 1.42) compared to individuals without TKR. The HR for femoral neck fracture 0–10 years after TKR was 0.95 (95% CI 0.89 to 1.01) and for trochanteric fracture was 1.13 (95% CI 1.06 to 1.21). The HR for hip fracture in the age group 50–74 was 1.28 (95% CI 1.14 to 1.43) and in the age group 75–90 years was 0.99 (95% CI 0.94 to 1.04) 0–10 years after TKR, compared to individuals without TKR. Conclusion Individuals had a low risk for hip fracture before TKR but an increased risk the first year after TKR. The risk in individuals below age 75 years and for trochanteric fractures was increased after TKR. Possible explanations include changed knee kinematics after a TKR, physical activity level, fall risk, and other unknown factors.

    更新日期:2020-01-04
  • Rib fractures after blunt thoracic trauma in patients with normal versus diminished bone mineral density: a retrospective cohort study
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-11
    J. T. H. Prins, E. M. M. Van Lieshout, M. R. L. Reijnders, M. H. J. Verhofstad, M. M. E. Wijffels

    Abstract This study aimed to evaluate rib fracture rate as well as rib fracture characteristics after thoracic trauma in patients with normal versus diminished bone mineral density (BMD). A retrospective cohort study of persons aged 50 years or older presenting to the Emergency Department after sustaining blunt thoracic trauma between July 1, 2014, and December 31, 2017, was performed. Patient and trauma characteristics and DXA scan results were collected. Rib fracture rate and characteristics were evaluated on a radiograph and/or CT scan of the thorax. In total, 119 patients were included for analysis. Fifty-eight of them (49%) had a diminished BMD. In the remaining 61, the BMD was normal. The diminished BMD group experienced rib fractures more often than the normal BMD group (n = 43 (74%) versus n = 31 (51%); p = 0.014). Patients with diminished BMD suffered low-energy trauma more frequently than the normal BMD group (21 (36%) versus 11 patients (15%), respectively (p = 0.011)). Rib fracture characteristics such as the median number of rib fractures, concomitant intrathoracic injury rate, and rib fracture type distribution were not different between the groups. The rate of rib fractures after blunt thoracic trauma was significantly higher in patients with diminished BMD than in patients with a normal BMD. Differences in number and location of rib fractures between groups could not be proven. When assessing patients aged 50 years or older presenting to the hospital after substantial blunt thoracic trauma, the presence of diminished BMD should be taken into account and the presence of rib fractures should be investigated with appropriate diagnostic procedures. Diminished bone mineral density (i.e., osteopenia or osteoporosis) is associated with increased fracture risk. This study evaluated if diminished BMD increases the rib fracture risk. Patients with diminished BMD have a higher risk of sustaining rib fractures after substantial blunt thoracic trauma, which implicates a lower threshold for CT imaging of the chest.

    更新日期:2020-01-04
  • Education intervention for older adults with osteoporosis: a systematic review
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-12-11
    Q. Y. Gai, H. Lv, Y. P. Li, Q. M. Fu, P. Li

    Abstract Background Various education interventions were developed for preventing or managing OP, but the effects of those interventions on older adults were inconclusive. Purpose This study evaluated the effectiveness of educational interventions in preventing osteoporosis in older adults. A literature search was performed in MEDLINE (PubMed), Cochrane Library, and CBM (China BioMed Database) from the initial date of each database to Oct 2016. Data Extraction Two investigators independently extracted essential data from qualified studies concerning the settings, population, interventions, follow-ups, and outcomes of interest, namely effects of bone mineral density tests, changes in behavior, knowledge increase, self-efficacy, medication adherence (calcium and vitamin D), and quality of life, respectively. Data Synthesis A total of 17 studies met the inclusion criteria and therefore were included in the current study. The overall quality of the included studies was moderate. We were unable to carry out a meta-analysis due to the heterogeneity of these studies. We fond that compared with control groups, patients’ knowledge of osteoporosis increased significantly (p < .05) through all five interventions, which included PowerPoint presentations and discussion, class-based educational programs, osteoporosis self-management courses, revised health belief model and classes, computerized support programs and brush-up courses. Limitation Studies included in the present study were all conducted in Western countries and only descriptive methods were applied in synthesis due to heterogeneity in interventions and outcomes. Conclusion Education interventions were effective in preventing osteoporosis in older adults. Future research should focus on approaching this issue quantitatively (i.e., through meta-analysis).

    更新日期:2020-01-04
  • Effects of physical and mind-body exercise on sleep problems during and after breast cancer treatment: a systematic review and meta-analysis.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-08
    Charlotte Kreutz,Martina E Schmidt,Karen Steindorf

    PURPOSE We conducted a meta-analysis evaluating the effects of different exercise interventions on self-reported and objective sleep measurements during or after breast cancer treatment. METHODS Three databases were systematically searched for randomized controlled trials with any type of exercise intervention in women with breast cancer. Outcomes were self-reported or objective sleep measurements. Standardized mean differences (SMDs) were calculated using random-effects models. RESULTS The meta-analysis included 22 trials with 2107 participants. Of these, 17 studies used the Pittsburgh Sleep Quality Index (PSQI), six studies included objective sleep assessments (ActiGraph). Physical exercise interventions included walking, aerobic exercise, resistance exercise or a combination of both. Mind-body exercise interventions included yoga, Tai Chi and Qigong. Most interventions were supervised. Both, physical (SMD - 0.32; 95% CI - 0.54 to - 0.10) and mind-body exercise interventions (SMD - 0.27; 95% CI - 0.44 to - 0.09), resulted in improvements of total sleep scores. Subgroup analyses revealed no clear differences between interventions conducted during versus after breast cancer treatment. Considering the PSQI subscales, exercise resulted in improvements of sleep quality (SMD - 0.28; 95% CI - 0.44 to - 0.11) and sleep disturbances (SMD - 0.26; 95% CI - 0.45 to - 0.06). Regarding the objective measurements, no significant effects were found. CONCLUSIONS Physical as well as mind-body exercise can improve subjective sleep problems in breast cancer patients. In contrast, there was no effect of exercise on objective sleep measures. Future studies should clarify which type of intervention might be most effective depending on individual patients' and treatments' characteristics.

    更新日期:2019-11-01
  • The orphan nuclear receptor estrogen-related receptor beta (ERRβ) in triple-negative breast cancer.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-11-20
    Aileen I Fernandez,Xue Geng,Krysta Chaldekas,Brent Harris,Anju Duttargi,V Layne Berry,Deborah L Berry,Akanksha Mahajan,Luciane R Cavalli,Balázs Győrffy,Ming Tan,Rebecca B Riggins

    PURPOSE Triple-negative breast cancer (TNBC)/basal-like breast cancer (BLBC) is a highly aggressive form of breast cancer. We previously reported that a small molecule agonist ligand for the orphan nuclear receptor estrogen-related receptor beta (ERRβ or ESRRB) has growth inhibitory and anti-mitotic activity in TNBC cell lines. In this study, we evaluate the association of ESRRB mRNA, copy number levels, and protein expression with demographic, clinicopathological, and gene expression features in breast tumor clinical specimens. METHODS ESRRB mRNA-level expression and clinical associations were analyzed using RNAseq data. Array-based comparative genomic hybridization determined ESRRB copy number in African-American and Caucasian women. Transcription factor activity was measured using promoter-reporter luciferase assays in TNBC cell lines. Semi-automatic quantification of immunohistochemistry measured ERRβ protein expression on a 150-patient tissue microarray series. RESULTS ESRRB mRNA expression is significantly lower in TNBC/BLBC versus other breast cancer subtypes. There is no evidence of ESRRB copy number loss. ESRRB mRNA expression is correlated with the expression of genes associated with neuroactive ligand-receptor interaction, metabolic pathways, and deafness. These genes contain G/C-rich transcription factor binding motifs. The ESRRB message is alternatively spliced into three isoforms, which we show have different transcription factor activity in basal-like versus other TNBC cell lines. We further show that the ERRβ2 and ERRβsf isoforms are broadly expressed in breast tumors at the protein level. CONCLUSIONS Decreased ESRRB mRNA expression and distinct patterns of ERRβ isoform subcellular localization and transcription factor activity are key features in TNBC/BLBC.

    更新日期:2019-11-01
  • Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2018-09-17
    Laura Spring,Andrzej Niemierko,Stephanie Haddad,Megan Yuen,Amy Comander,Kerry Reynolds,Jennifer Shin,Atul Bahn,Elena Brachtel,Michelle Specht,Barbara L Smith,Alphonse Taghian,Rachel Jimenez,Jeffrey Peppercorn,Steven J Isakoff,Beverly Moy,Aditya Bardia

    PURPOSE Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. METHODS We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis. RESULTS In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. CONCLUSIONS Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

    更新日期:2019-11-01
  • CCN6 regulates IGF2BP2 and HMGA2 signaling in metaplastic carcinomas of the breast.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2018-09-17
    Emily R McMullen,Maria E Gonzalez,Stephanie L Skala,Mai Tran,Dafydd Thomas,Sabra I Djomehri,Boris Burman,Kelley M Kidwell,Celina G Kleer

    PURPOSE Metaplastic breast carcinomas are an aggressive subtype of triple-negative breast cancer (TNBC) in which part or all of the adenocarcinoma transforms into a non-glandular component (e.g., spindled, squamous, or heterologous). We discovered that mammary-specific Ccn6/Wisp3 knockout mice develop mammary carcinomas with spindle and squamous differentiation that share upregulation of the oncofetal proteins IGF2BP2 (IMP2) and HMGA2 with human metaplastic carcinomas. Here, we investigated the functional relationship between CCN6, IGF2BP2, and HMGA2 proteins in vitro and in vivo, and their expression in human tissue samples. METHODS MMTV-cre;Ccn6fl/fl tumors and spindle TNBC cell lines were treated with recombinant CCN6 protein or vehicle. IGF2BP2 was downregulated using shRNAs in HME cells with stable CCN6 shRNA knockdown, and subjected to invasion and adhesion assays. Thirty-one human metaplastic carcinomas were arrayed in a tissue microarray (TMA) and immunostained for CCN6, IGF2BP2, and HMGA2. RESULTS CCN6 regulates IGF2BP2 and HMGA2 protein expression in MMTV-cre;Ccn6fl/fl tumors, in MDA-MB-231 and - 468, and in HME cells. CCN6 recombinant protein reduced IGF2BP2 and HMGA2 protein expression, and decreased growth of MMTV-cre;Ccn6fl/fl tumors in vivo. IGF2BP2 shRNA knockdown was sufficient to reverse the invasive abilities conferred by CCN6 knockdown in HME cells. Analyses of the TCGA Breast Cancer Cohort (n = 1238) showed that IGF2BP2 and HMGA2 are significantly upregulated in metaplastic carcinoma compared to other breast cancer subtypes. In clinical samples, low CCN6 is frequent in tumors with high IGF2BP2/HMGA2 with spindle and squamous differentiation. CONCLUSIONS These data shed light into the pathogenesis of metaplastic carcinoma and demonstrate a novel CCN6/IGF2BP2/HMGA2 oncogenic pathway with biomarker and therapeutic implications.

    更新日期:2019-11-01
  • Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927).
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2018-08-31
    Sherry Shen,Joseph M Unger,Katherine D Crew,Cathee Till,Heather Greenlee,Julie Gralow,Shaker R Dakhil,Lori M Minasian,James L Wade,Michael J Fisch,N Lynn Henry,Dawn L Hershman

    PURPOSE Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. METHODS We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I-III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0-10). RESULTS Among the 249 participants, 139 had BMI < 30 kg/m2 (56%) and 110 had BMI ≥ 30 kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively). CONCLUSIONS In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

    更新日期:2019-11-01
  • Obesity and mortality after locoregional breast cancer diagnosis.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2018-08-31
    A Holliston Moore,Amy Trentham-Dietz,Marguerite Burns,Ronald E Gangnon,Caprice C Greenberg,David J Vanness,John Hampton,Xiao-Cheng Wu,Roger T Anderson,Joseph Lipscomb,Gretchen G Kimmick,Rosemary Cress,J Frank Wilson,Susan A Sabatino,Steven T Fleming

    PURPOSE Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. METHODS Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. RESULTS In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m2 difference in BMI = 0.85, 95% CI 0.75-0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35 kg/m2 vs. 18.5-24.9 kg/m2 = 4.74, 95% CI 1.78-12.59). CONCLUSIONS Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

    更新日期:2019-11-01
  • IgA Fc-folate conjugate activates and recruits neutrophils to directly target triple-negative breast cancer cells.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2018-08-30
    Eric D Frontera,Rafa M Khansa,Dana L Schalk,Lauren E Leakan,Tracey J Guerin-Edbauer,Manohar Ratnam,David H Gorski,Cecilia L Speyer

    PURPOSE According to the American Cancer Society, 1 in 8 women in the U.S. will develop breast cancer, with triple-negative breast cancer (TNBC) comprising 15-20% of all breast cancer cases. TNBC is an aggressive subtype due to its high metastatic potential and lack of targeted therapy. Recently, folate receptor alpha (FRA) is found to be expressed on 80% of TNBC with high expression correlating with poor prognosis. In this study, we examined whether binding IgA Fc-folate molecules to FRA receptors on TNBC cells can elicit and induce neutrophils (PMNs), by binding their FcαR1 receptors, to destroy TNBC cells. METHODS FRA was analyzed on TNBC cells and binding assays were performed using 3H-folate. Fc-folate was synthesized by linking Fc fragments of IgA via amine groups to folate. Binding specificity and antibody-dependent cellular cytotoxicity (ADCC) potential of Fc-folate to FcαR1 were confirmed by measuring PMN adhesion and myeloperoxidase (MPO) release in a cell-based ELISA. Fc-folate binding to FRA-expressing TNBC cells inducing PMNs to destroy these cells was determined using 51Cr-release and calcein-labeling assays. RESULTS Our results demonstrate expression of FRA on TNBC cells at levels consistent with folate binding. Fc-folate binds with high affinity to FRA compared to whole IgA-folate and induces MPO release from PMN when bound to FcαR1. Fc-folate inhibited binding of 3H-folate to TNBC cells and induced significant cell lysis of TNBC cells when incubated in the presence of PMNs. CONCLUSION These findings support the hypothesis that an IgA Fc-folate conjugate can destroy TNBC cells by eliciting PMN-mediated ADCC.

    更新日期:2019-11-01
  • Histone deacetylase (HDAC) inhibitors and doxorubicin combinations target both breast cancer stem cells and non-stem breast cancer cells simultaneously.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : null
    Ling-Wei Hii,Felicia Fei-Lei Chung,Jaslyn Sian-Siu Soo,Boon Shing Tan,Chun-Wai Mai,Chee-Onn Leong

    PURPOSE Breast cancer stem cells (CSCs) are a small subpopulation of cancer cells that have high capability for self-renewal, differentiation, and tumor initiation. CSCs are resistant to chemotherapy and radiotherapy, and are responsible for cancer recurrence and metastasis. METHODS By utilizing a panel of breast cancer cells and mammospheres culture as cell-based screening platforms, we performed high-throughput chemical library screens to identify agents that are effective against breast CSCs and non-CSCs. The hit molecules were paired with conventional chemotherapy to evaluate the combinatorial treatment effects on breast CSCs and non-CSCs. RESULTS We identified a total of 193 inhibitors that effectively targeting both breast CSCs and non-CSCs. We observed that histone deacetylase inhibitors (HDACi) synergized conventional chemotherapeutic agents (i.e., doxorubicin and cisplatin) in targeting breast CSCs and non-CSCs simultaneously. Further analyses revealed that quisinostat, a potent inhibitor for class I and II HDACs, potentiated doxorubicin-induced cytotoxicity in both breast CSCs and non-CSCs derived from the basal-like (MDA-MB-468 and HCC38), mesenchymal-like (MDA-MB-231), and luminal-like breast cancer (MCF-7). It was also observed that the basal-like breast CSCs and non-CSCs were more sensitive to the co-treatment of quisinostat with doxorubicin compared to that of the luminal-like breast cancer subtype. CONCLUSION In conclusion, this study demonstrates the potential of HDACi as therapeutic options, either as monotherapy or in combination with chemotherapeutics against refractory breast cancer.

    更新日期:2019-11-01
  • The influence on quality of life of intermittent scheduling in first- and second-line chemotherapy of patients with HER2-negative advanced breast cancer.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : null
    Anouk K M Claessens,Reinier Timman,Jan J Busschbach,Jeanette M Bouma,Jeany M Rademaker-Lakhai,Frans L G Erdkamp,Vivianne C G Tjan-Heijnen,Monique E M M Bos,

    BACKGROUND The Stop&Go study randomized patients with advanced breast cancer to intermittent (two times four) or continuous (eight subsequent cycles) first- and second-line chemotherapy. METHODS QoL was measured with RAND-36 questionnaires every 12 weeks. The primary objective was to estimate differences in changes from baseline between intermittent and continuous treatment. An effect size of 0.5 SD (5 points) was considered clinically meaningful. RESULTS A total of 398 patients were included with a median follow-up of 11.4 months (IQR 5.6-22.2). Mean physical QoL baseline scores were 38.0 resp. 38.2, and mental scores 45.0 resp. 42.4 for intermittent and continuous treatment. Physical QoL declined linearly in the intermittent arm causing a clinically meaningful difference of 5.40 points at 24 months (p < 0.001), while scores in the continuous arm stabilized after a small decline of ± 3.4 points at 12 months. Conversely, mental QoL was fairly stable and even improved with 1.58 (p = 0.005) and 2.48 points (p < 0.001) at 12 months for intermittent and continuous treatment, respectively. When comparing arms for both components in changes from baseline, the maximum differences were 2.46 (p = 0.101) and 1.95 points (p = 0.182) for physical and mental scores, both measured at 30 months and in favor of continuous treatment. CONCLUSION Intermittent first- and second-line chemotherapy in patients with HER2-negative advanced breast cancer showed a trend for worse impact on QoL compared to continuous chemotherapy, with neither significant nor meaningful differences in course. We recommend prescribing chemotherapy continuously until progressive disease or unacceptable toxicity. Trial registration EudraCT 2010-021519-18; BOOG 2010-02.

    更新日期:2019-11-01
  • Breast density measured volumetrically in a clinical environment: cross-sectional study with photon counting technology.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : null
    Jean L Browne,Lilian Casas,Guillermo Santandreu,Ignacio Rodriguez,Beatriz Navarro,Francesc Tresserra,M Angela Pascual

    OBJECTIVE Mammographic breast density (BDen), the ratio of glandular volume (GVol) to breast volume (BVol), is the second most prevalent risk factor for breast cancer (BC). Newly developed photon counting technology allows precise and systematic measurements in clinical practice. Our objective is to see how these parameters change with age in women with and without cancer. MATERIALS AND METHODS This retrospective study analyzed results of BDen, GVol, and BVol in 64,182 mammograms performed with photon counting technology on 32,448 consecutive women from April 2014 to December 2015. Only their first study was included. We excluded women with incomplete data or with breast implants. RESULTS Mean age of women without BC diagnosed during the study period was 52.1 ± 9.9. BC and was found in 263 women (0.81%). Mean age was 53.0 ± 10.4. BDen, GVol, and BVol were 14%, 24%, and 2% greater in women with BC (P < 0.001 for BDen and GVol and P = 0.02 for BVol). BDen and GVol diminished following similar patterns across age in both groups, with soft slopes before and after a steep drop from 50 to 60, probably due to menopause. CONCLUSION BDen diminishes with age in women with or without BC, but it is generally higher in women with BC. GVol could be a more robust indicator associated with BC risk than BDen. This technology can ease the way to studies of interventions to diminish BDen (or GVol) in the hope of diminishing BC incidence or predict if longitudinal changes are indicative of impending cancer.

    更新日期:2019-11-01
  • Pre- and post-diagnostic intake of whole grain and dairy products and breast cancer prognosis: the Danish Diet, Cancer and Health cohort.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : null
    Julie Louise Munk Andersen,Louise Hansen,Birthe Lykke Riegels Thomsen,Lisa Rudolph Christiansen,Lars Ove Dragsted,Anja Olsen

    PURPOSE Fiber rich foods and dairy products have been suggested to be associated with breast cancer prognosis, though existing research is limited and either report on pre- or post-diagnostic dietary intake in relation to breast cancer prognosis. We investigated the associations between intake of whole grain (WG) and dairy products assessed both pre- and post-diagnostically in relation to breast cancer prognosis. METHODS A total of 1965 women from the Diet, Cancer and Health cohort who were diagnosed with breast cancer between baseline (1993-1997) and December 2013 were included and followed for a median of 7 years after diagnosis. During follow-up, 309 women experienced breast cancer recurrence and 460 women died, of whom 301 died from breast cancer. Dietary assessment by food frequency questionnaires was obtained up to three times, pre- and post-diagnostic, over a period of 18 years. Cox proportional hazard models were used to estimate hazard ratios. RESULTS No associations were observed between pre- or post-diagnostic intake of total WG or total dairy products and breast cancer prognosis. A high pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality (HR 0.76, 95% CI 0.59-0.99), whereas high post-diagnostic intake of rye bread was associated with higher breast cancer-specific mortality (HR 1.29, 95% CI 1.02-1.63). A generally high intake of cheese was associated with a higher recurrence rate. CONCLUSION Pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality, and post-diagnostic intake of rye bread was associated with higher breast cancer specific mortality.

    更新日期:2019-11-01
  • Noncompliance with palliative systemic therapy in patients with distant metastatic breast cancer: a blind spot for oncologists?
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-05-03
    Constanze Elfgen,Giacomo Montagna,Seraina Margaretha Schmid,Walter Bierbauer,Uwe Güth

    PURPOSE The goal of our study was to provide a general overview of noncompliance with palliative systemic therapy in distant metastatic breast cancer (MBC). METHODS We analyzed an unselected cohort of 339 patients who were diagnosed with MBC over a 22-year period (1990-2011, age restriction: ≥ 85 years old). RESULTS Forty patients (11.8%) rejected the offered or recommended systemic therapy (age distribution of this noncompliance subgroup: ≤60 years at MBC diagnosis: 7.9%; 60-70 years: 13.2%; > 70 years: 15.6%). The rate of noncompliance was equally distributed over time (1990-1999: 12.2% vs. 2000-2011: 11.5%, p = 0.87). Compared to patients who had received palliative antineoplastic systemic therapy, those who remained untreated were significantly older (70 vs. 61 years, p = 0.015), had shorter metastatic disease survival (2 vs. 27 months, p < 0.001), had more often an aggressive tumor subtype (hormone-receptor negative carcinomas: 48.7% vs. 22.2%, p < 0.001), and had more often secondary MBC (95.0% vs. 73.6%, p = 0.001). CONCLUSIONS Although the high rate of noncompliance in the subgroup of elderly patients was not unexpected, it is noticeable that even in the subgroup of patients who were younger than 60 years, approximately 8% also rejected any systemic therapy before a MBC-related death occurred This group of younger women rarely had any relevant comorbidities, were potential candidates for chemotherapy and knowingly declined the therapy options. Such patients are never or seldom seen by oncologists in their daily practice and therefore play a minor role in their personal perception of disease. Nevertheless, these under-reported cases make up a significant proportion of MBC.

    更新日期:2019-11-01
  • Circulating adipose stromal cells as a response biomarker in phase II energy balance trials of obese breast cancer survivors and high-risk women.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-05-02
    Hailey A Baker,Carol J Fabian,Richard C Hastings,Dan A Dixon,Jennifer L Nydegger,Teresa A Phillips,Kandy R Powers,Bruce F Kimler

    PURPOSE Circulating adipose stromal cells (CASC) are thought to be increased in obesity and facilitate angiogenesis, and tumor metastases. METHODS CASC were identified from buffy coat peripheral blood mononuclear cells (PBMCs) by flow cytometry as CD34brightCD31- CD45- and CASC frequency was compared to adiposity measures in 33 women at increased risk for breast cancer. Feasibility of CASC as a response biomarker for a diet and exercise intervention in ten breast cancer survivors was then explored. RESULTS For 33 high-risk women, median CASC frequency was 9.7 per million PBMCs and trended positively with body mass index, fat mass index (FMI), and percent android fat. Correlation was significant when BMI was dichotomized at > versus < 35 kg/m2 (p = 0.02). For ten breast cancer survivors with a median BMI of 37 kg/m2, median CASC frequency was 16.4 per million PBMCs. In univariate analyses, change in BMI, total fat and visceral fat were significantly correlated with change in CASC frequency. On multivariate analysis, change in visceral adipose had the strongest association with change in CASC frequency (p < 0.00078). CONCLUSIONS The association between the reduction in visceral adipose tissue and the decrease in frequency of circulating adipose stromal cells suggests that the latter might be a useful biomarker in clinical trials of obese breast cancer survivors undergoing a weight loss intervention.

    更新日期:2019-11-01
  • Establishing physical activity in breast cancer: self-report versus activity tracker.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-05-02
    Chad W Wagoner,Seul K Choi,Allison M Deal,Jordan T Lee,William A Wood,Hyman B Muss,Kirsten A Nyrop

    PURPOSE Establishing accurate estimates of physical activity at baseline is essential for interventions assessing the potential benefits of exercise in adults with cancer. This study compares self-reported physical activity with independent data from activity trackers in women with early breast cancer (BC) recruited into a "walking" intervention during chemotherapy. METHODS Baseline (pre-intervention) questions inquired about self-reported physical activity-number of walking days/week and minutes/day-in women who were initiating chemotherapy for Stage I-III BC. Activity trackers measured steps per day during the first full week of chemotherapy. Weighted Kappa statistic and Pearson correlation coefficients were used to evaluate agreement and association between self-reported and objectively tracked physical activity levels, respectively. Univariate analyses were conducted to identify variables that may influence congruence between the two measures. RESULTS In a sample of 161 women, 77% were white, with mean age 56 years. Agreement between self-reported and objectively tracked physical activity was "fair" (kappa coefficient = 0.31), with most patients (59%) over-reporting their physical activity levels. There was weak correlation between the two measures (r = 0.24); however, correlation was strong in participants who were not married (r = 0.53) and/or living alone (r = 0.69). CONCLUSIONS Objective methods for assessing physical activity (activity trackers, accelerometers) should be used as a complement to self-reported measures to establish credible activity levels for intervention studies seeking to increase physical activity and/or measure the impact of increased physical activity in women with breast cancer.

    更新日期:2019-11-01
  • Prediction of chemotherapy benefit by EndoPredict in patients with breast cancer who received adjuvant endocrine therapy plus chemotherapy or endocrine therapy alone.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-05-02
    Ivana Sestak,Miguel Martín,Peter Dubsky,Ralf Kronenwett,Federico Rojo,Jack Cuzick,Martin Filipits,Amparo Ruiz,William Gradishar,Hatem Soliman,Lee Schwartzberg,Richard Buus,Dominik Hlauschek,Alvaro Rodríguez-Lescure,Michael Gnant

    PURPOSE EndoPredict (EPclin) is a prognostic test validated to inform decisions on adjuvant chemotherapy to endocrine therapy alone for patients with oestrogen receptor-positive, HER2-negative breast cancer. Here, we determine the performance of EPclin for estimating 10-year distant recurrence-free interval (DRFI) rates for those who received adjuvant endocrine therapy (ET) alone compared to those with chemotherapy plus endocrine therapy (ET + C). METHODS A total of 3746 women were included in this joint analysis. 2630 patients received 5 years of ET alone (ABCSG-6/8, TransATAC) and 1116 patients received ET + C (GEICAM 2003-02/9906). The primary objective was to evaluate the ability of EPclin to provide an estimate of the 10-year DR rate as a continuous function of EPclin separately for ET alone and ET + C. Cox proportional hazard models were used for these analyses. RESULTS EPclin was highly prognostic for DR in women who received ET alone (HR 2.79 (2.49-3.13), P < 0.0001) as well as in those who received ET + C (HR 2.27 (1.99-2.59), P < 0.0001). Women who received ET + C had significantly smaller increases in 10-year DR rates with the increasing EPclin score than those receiving ET alone (EPclin = 5; 12% ET + C vs. 20% ET alone). We observed a significant positive interaction between EPclin and treatment groups (P-interaction = 0.022). CONCLUSIONS In this comparative non-randomised analysis, the rate of increase in DR with EPclin score was significantly reduced in women who received ET + C versus ET alone. Our indirect comparisons suggest that a high EPclin score can predict chemotherapy benefit in women with ER-positive, HER2-negative disease.

    更新日期:2019-11-01
  • The influence of neoadjuvant chemotherapy on complications of immediate DIEP flap breast reconstructions.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-29
    J Beugels,J L W Meijvogel,S M H Tuinder,V C G Tjan-Heijnen,E M Heuts,A Piatkowski,R R W J van der Hulst

    PURPOSE The impact of neoadjuvant chemotherapy on the surgical outcomes of immediate breast reconstruction remains controversial. The aim of this study was to analyze the incidence of complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstructions in patients who received neoadjuvant chemotherapy compared to patients without neoadjuvant chemotherapy prior to surgery. METHODS A multicenter, retrospective cohort study was conducted of all patients who underwent immediate DIEP flap breast reconstruction between January 2010 and June 2017. Patients were divided in two groups as breast reconstructions with or without neoadjuvant chemotherapy, respectively. The primary outcome was the incidence of postoperative flap re-explorations, recipient-site complications and donor-site complications. RESULTS In total 432 immediate DIEP flap breast reconstructions in 326 patients were included. Forty-eight patients (n = 67 flaps) received neoadjuvant chemotherapy prior to immediate breast reconstruction and 278 patients (n = 365 flaps) did not. No statistically significant differences for any major (4.5% vs. 10.4%; p = 0.175) or minor (16.4% vs. 24.7%; p = 0.191) recipient-site complication were observed. Donor-site complications were recorded in 9 (18.8%) and 62 (22.2%) patients, respectively (p = 0.587). There was no difference in need for flap re-exploration between groups (3.0% vs. 8.5%; p = 0.139). Correction for potential confounding variables did not result in significant differences. CONCLUSIONS This study demonstrated similar complication rates for patients with and without neoadjuvant chemotherapy prior to immediate breast reconstruction, indicating that it is safe to perform an immediate DIEP flap breast reconstruction after neoadjuvant chemotherapy.

    更新日期:2019-11-01
  • Dose intensity in anthracycline-based chemotherapy for metastatic breast cancer: mature results of the randomised clinical trial ANZ 9311.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-28
    Stephen P Ackland,V Gebski,N Zdenkowski,A Wilson,M Green,S Tees,H Dhillon,G Van Hazel,J Levi,R J Simes,J F Forbes,A S Coates,

    PURPOSE The separate impacts of dose and dose intensity of chemotherapy for metastatic breast cancer remain uncertain. The primary objective of this trial was to compare a short, high-dose, intensive course of epirubicin and cyclophosphamide (EC) with a longer conventional dose regimen delivering the same total dose of chemotherapy. METHODS This open label trial randomised 235 women with metastatic breast cancer to receive either high-dose epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75 mg/m2 and cyclophosphamide 750 mg/m2 every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life. RESULTS In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P = 0.19) or overall survival (14.5 vs. 16.5 months, P = 0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity. CONCLUSION For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy. Australian Clinical Trials Registry registration number ACTRN12605000478617.

    更新日期:2019-11-01
  • Racial disparities in surveillance mammography among older breast cancer survivors.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-28
    Jimmitti Teysir,Nana Gegechkori,Juan P Wisnivesky,Jenny J Lin

    BACKGROUND Despite lower incidence rates among black women and a national decline in breast cancer (BC) deaths, there is a widening gap in BC mortality rates between black and white women in the United States. A previous study evaluating data from 1992 to 1999 found a racial disparity in the receipt of surveillance mammography. We sought to evaluate whether this disparity persists between black and white women diagnosed with BC between 2000 and 2011. METHODS Using the SEER-Medicare registry, we conducted an analysis of women ≥ 66 years diagnosed with early-stage (0-III) BC between 2000 and 2011 who underwent BC surgery. The primary outcome was receipt of surveillance mammography within 12 months of surgery. Chi square analyses were used to compare characteristics between black and white women. Multivariate logistic regression was used to assess receipt of surveillance mammography after controlling for potential confounders. RESULTS There were 3353 black and 40,564 white women in the final cohort. After adjusting for confounders, black women were still 24% less likely than white women to receive surveillance mammography (Odds ratio 0.76, 95% CI 0.70-0.0.82). Those who were married, younger, in the highest income quartile, diagnosed at earlier stages, had a lower comorbidity score, or who resided in metropolitan areas were more likely to receive surveillance mammography (p < 0.05). CONCLUSION(S) We found that older black BC survivors continue to experience lower rates of surveillance mammography, even after adjusting for multiple potential confounders. There remains a need to investigate which individual and systemic factors affect disparities in breast cancer care.

    更新日期:2019-11-01
  • Prognostic role of body mass index is different according to menopausal status and tumor subtype in breast cancer patients.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-28
    Jung Youn Kim,Dae-Won Lee,Kyung-Hun Lee,Ahrum Min,Han Suk Ryu,Han-Byoel Lee,Hyeong-Gon Moon,Tae-Yong Kim,Sae-Won Han,Do-Youn Oh,Wonshik Han,In Ae Park,Dong-Young Noh,Seock-Ah Im,Sukil Kim

    PURPOSE Although controversial, obesity and underweight may have a negative impact on breast cancer outcome. However, the relationship between body mass index (BMI) and breast cancer outcomes according to tumor subtype and menopausal status remains unclear. METHODS This study investigated the association between BMI and breast cancer outcome in stage I-III breast cancer patients. The relationships were further evaluated according to tumor subtype and menopausal status. RESULTS A total of 5919 patients, 3475 (58.7%) hormone receptor (HR)(+) human epidermal growth factor receptor 2 (HER2)(-), 608 (10.3%) HR(+)HER2(+), 621 (10.5%) HR(-)HER2(+), and 1079 (18.2%) HR(-)HER2(-) were included. Underweight and obesity had a negative impact on relapse-free survival but did not affect overall survival. Importantly, the prognostic role of BMI was different according to tumor subtype and menopausal status. In HR(+)HER2(-) patients, underweight was associated with poor relapse-free survival and overall survival in pre-menopausal women. In contrast, obesity had negative impact on relapse-free survival and overall survival in HR(+)HER2(-) post-menopausal patients. Underweight may have a negative prognostic role in HR(+)HER2(+) patients. However, BMI did not impact the outcome of HR(-)HER2(+) and HR(-)HER2(-) patients. CONCLUSIONS The impact of BMI on breast cancer outcome was dependent on tumor subtype and menopausal status. In HR(+)HER2(-) patients, underweight and obesity had a negative prognostic role in pre-menopausal and post-menopausal women, respectively. These findings in Asian population should be further evaluated and compared in Western population.

    更新日期:2019-11-01
  • Shared-patient physician networks and their impact on the uptake of genomic testing in breast cancer.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-28
    Jason Rotter,Lauren Wilson,Melissa A Greiner,Craig E Pollack,Michaela Dinan

    BACKGROUND Factors influencing the adoption of genomic testing are poorly understood, which may lead to inequitable and suboptimal treatment in cancer patients. Oncotype DX (ODX) is one of the first and most widely used genomic assays to stratify risk in women with early-stage breast cancer (BC). Physician networks have emerged as a significant and modifiable driver of emerging medical technology adoption. OBJECTIVE To investigate the association between physician network connections and the use of ODX testing. METHODS A retrospective study of women diagnosed with BC using SEER-Medicare from 2008 to 2012 was used. Medical oncologists were "connected" if they shared two or more patients during the early-adoption period (2008-2009). Parallel physician- and patient-level analyses employed logistic mixed models to determine the impact of being "connected" to an early-adopting oncologist on ODX use in 2011-2012. RESULTS 24,463 women met study criteria; 12,874 were diagnosed with BC in the early-adoption time period. 2129 medical oncologists treated these patients from 2008 to 2009. Medical oncologists had a median number of peer connections of 4 (IQR: 2-7). Peer connection to an early-adopting provider in 2008-2009 was associated with a 1.7-fold increase in providers' adopting ODX (95% CI: 1.1-2.6) and a 1.5-fold increase in their patients receiving ODX (95% CI: 1.1-2.0) in 2010-2012. CONCLUSIONS Peer connectedness to an early-adopting physician predicts ODX adoption in both physician-level and patient-level analyses. Provider networks may provide a potent and modifiable means to modulate the diffusion of emerging medical technologies. Efforts to increase testing, where appropriate, may benefit from peer-to-peer-based connection strategies.

    更新日期:2019-11-01
  • The impact of communication style on patient satisfaction.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-27
    Amelia A Trant,Borbala Szekely,Sarah S Mougalian,Michael P DiGiovanna,Tara Sanft,Erin Hofstatter,Andrea Silber,Kerin B Adelson,Anees Chagpar,Brigid Killelea,Nina Horowitz,Donald Lannin,Tristen Park,Michelle Corso,Gineesha Abraham,Karen Pollard-Murphy,Tracy Sturrock,Elspeth Knill-Selby,Ashley Western,Camille Servodidio,Marios Konstantinos Tasoulis,Barbara Healy,Christos Hatzis,Lajos Pusztai

    BACKGROUND Communication between patients and health providers influences patient satisfaction, but it is unknown whether similarity in communication styles results in higher patient satisfaction. METHODS This study was conducted in the Smilow Cancer Hospital Breast Center. During routine follow-up visits, patients completed a Communication Styles Assessment (CSA), health survey (SF-12), Princess Margaret Hospital Satisfaction with Doctor Questionnaire, and brief demographic form. Physicians and Advanced Practice Providers were also asked to complete the CSA. Patients and providers were blinded to each other's responses. A communication styles concordance score was calculated as the Pearson correlation between 80 binary CSA items for each provider/patient pair. Factors affecting patient satisfaction scores were assessed in mixed-effects models. RESULTS In total, 330 patients were invited to participate; of these 289 enrolled and 245 returned surveys. One hundred seventy-four completed all survey components, and 18 providers completed the CSA. Among the factors considered, physical health score (effect size = 0.0058, 95% CI 0.00051 to 0.0011, p = 0.032) and employment status (0.12, 95% CI - 0.0094 to 0.25, p = 0.069) had the greatest impact on patient satisfaction. However, patients who were not employed and less physically healthy had significantly elevated satisfaction scores when their communication style was more similar to their provider's (1.52, 95% CI 0.66 to 2.38, p = 0.0016). CONCLUSIONS Patients who were physically healthy and employed were generally more satisfied with their care. The similarity in communication styles of patients and providers had a greater impact on patient satisfaction for patients who were less physically healthy and not employed.

    更新日期:2019-11-01
  • Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-27
    Anna Weiss,Heather Lin,Gildy V Babiera,Isabelle Bedrosian,Simona F Shaitelman,Yu Shen,Henry M Kuerer,Elizabeth A Mittendorf,Abigail S Caudle,Kelly K Hunt,Rosa F Hwang

    PURPOSE The optimal management of breast cancer patients with a positive sentinel lymph node (SLN) who undergo mastectomy remains controversial. This study aimed to describe treatment patterns of patients with positive SLNs who undergo mastectomy using a large population-based database. METHODS The NCDB was queried for cT1-2N0 breast cancer patients treated with mastectomy between 2006 and 2014 who had 1-2 positive SLNs. Patients receiving neoadjuvant chemotherapy were excluded. Axillary management included SLN dissection (SLND) alone, axillary lymph node dissection (ALND), post-mastectomy radiation (PMRT) alone, and ALND + PMRT. Trends of axillary management and patient characteristics were examined. RESULTS Among 12,190 patients who met study criteria, the use of ALND dropped with a corresponding increase in other approaches. In 2006, 34% of patients had SLND alone, 47% ALND, 8% PMRT and 11% ALND + PMRT. By 2014, 37% had SLND, 23% ALND, 27% PMRT and 13% ALND + PMRT. Patients who underwent SLND alone were older (mean 60.6 years) with more comorbidities (Charlson-Deyo score > 2), smaller primary tumors (mean 2.1 cm), well-differentiated histology, hormone receptor-positive, HER2-negative tumors, without lymphovascular invasion (all P values < 0.01). Treatment with SLND alone was more likely if patients had only one positive SLN (P < 0.001) or micrometastatic disease (P < 0.001), and were treated at community centers compared with academic centers (P < 0.001). CONCLUSIONS The management of breast cancer patients undergoing mastectomy with positive SLNs has evolved over time with decreased use of ALND and increased use of radiation. Some patient subsets are underrepresented in recent clinical trials, and therefore, future trials should focus on these patients.

    更新日期:2019-11-01
  • Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-26
    Maysa M Abu-Khalaf,Anton Safonov,Jamie Stratton,Shiyi Wang,Christos Hatzis,Esther Park,Lajos Pusztai,Cary P Gross,Raymond Russell

    BACKGROUND There is a lack of consensus to guide which breast cancer patients require left ventricular function assessment (LVEF) prior to anthracycline therapy; the cost-effectiveness of screening this patient population has not been previously evaluated. METHODS We performed a retrospective analysis of the Yale Nuclear Cardiology Database, including 702 patients with baseline equilibrium radionuclide angiography (ERNA) scan prior to anthracycline and/or trastuzumab therapy. We sought to examine associations between abnormal baseline LVEF and potential cardiac risk factors. Additionally, we designed a Markov model to determine the incremental cost-effectiveness ratio (ICER) of ERNA screening for women aged 55 with stage I-III breast cancer from a payer perspective over a lifetime horizon. RESULTS An abnormal LVEF was observed in 2% (n = 14) of patients. There were no significant associations on multivariate analysis performed on self-reported risk factors. Our analysis showed LVEF screening is cost-effective with ICER of $45,473 per QALY gained. For a willingness-to-pay threshold of $100,000/ QALY, LVEF screening had an 81.9% probability of being cost-effective. Under the same threshold, screening was cost-effective for non-anthracycline cardiotoxicity risk of RR ≤ 0.58, as compared to anthracycline regimens. CONCLUSIONS Age, preexisting cardiac risk factors and coronary artery disease did not predict a baseline abnormal LVEF. While the prevalence of an abnormal baseline LVEF is low in patients with breast cancer, our results suggest that cardiac screening prior to anthracycline is cost-effective.

    更新日期:2019-11-01
  • Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study.
    Breast Cancer Res. Treat. (IF 3.471) Pub Date : 2019-04-26
    Hak Min Lee,Bo Wook Kim,Seho Park,Sungmin Park,Jeon Eon Lee,Young Jin Choi,Sung Yong Kim,Sang Uk Woo,Hyun Jo Youn,Ilkyun Lee

    PURPOSE Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset. METHODS Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls. RESULTS Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively. CONCLUSIONS We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.

    更新日期:2019-11-01
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