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1.
J Intellect Disabil Res ; 68(5): 524-536, 2024 May.
Article En | MEDLINE | ID: mdl-38350666

BACKGROUND: Individuals with intellectual disabilities (IDs) often present deficiencies in motor, balance and postural control. On the other hand, the practice of physical activity and dance usually reduces these deficiencies. Therefore, in this study, we aimed to compare the control of the centre of pressure (COP) in people with Down syndrome (DS) or other causes of ID in relation to people without disabilities and to observe the influence of vision and the practice of dance. METHODS: This cross-sectional study analyses the COP in a static standing position with open and closed eyes in four study groups. A total of 273 people were recruited (80 adults without ID, 46 adults with DS, 120 adults with other causes of ID and 27 dancers with DS). RESULTS: A greater area of oscillation and path of the COP was observed in the participants with ID compared with the participants without ID, especially in the sway area of the COP. The oscillation speed of the COP was also higher. When analysing the displacement of the COP, anteroposterior and mediolateral components, there were also differences, except when comparing the group of dancers with DS with respect to the group without ID. The visual condition only influenced the group of participants without disabilities. CONCLUSIONS: The results of our study show that there is a less efficient static postural control in people with ID, as greater displacements were observed in the COP of the participants with ID. The differences in some specific variables that analyse the displacement of the COP were smaller when comparing the group of dancers with DS and the individuals without ID.


Dancing , Down Syndrome , Intellectual Disability , Adult , Humans , Cross-Sectional Studies , Postural Balance
2.
ESMO Open ; 7(2): 100426, 2022 04.
Article En | MEDLINE | ID: mdl-35334418

BACKGROUND: Statins are cholesterol-lowering drugs prescribed for the prevention and treatment of cardiovascular disease. Moreover, statins may possess anticancer properties and interact with receptor activator of nuclear factor κB ligand expression. We aimed at evaluating a hypothetical synergistic effect of statins with denosumab in early-stage breast cancer (BC) patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 18. PATIENTS AND METHODS: ABCSG-18 (NCT00556374) is a prospective, randomized, double-blind, phase III study; postmenopausal patients with hormone receptor-positive BC receiving a nonsteroidal aromatase inhibitor were randomly assigned to denosumab or placebo. In this post hoc analysis, we investigated the effects of concomitant statin therapy on recurrence risk (RR) of BC, fracture risk and bone mineral density (BMD). RESULTS: In the study population (n = 3420), statin therapy (n = 824) was associated with worse disease-free survival (DFS) [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.04-1.75; P = 0.023]. While no significant effect of lipophilic statins (n = 710) on RR was observed (HR 1.30, 95% CI 0.99-1.72; P = 0.062), patients on hydrophilic statins (n = 87) had worse DFS compared with patients not receiving any statins (HR 2.00, 95% CI 1.09-3.66; P = 0.026). This finding was mainly driven by the effect of hydrophilic statins on DFS in the denosumab arm (HR 2.63, 95% CI 1.21-5.68; P = 0.014). However, this effect subsided after correction for confounders in the sensitivity analysis. No association between statin use and fracture risk or osteoporosis was observed. CONCLUSION: According to this analysis, hydrophilic statins showed a detrimental effect on DFS in the main model, which was attenuated after correction for confounders. Our data need to be interpreted with caution due to their retrospective nature and the low number of patients receiving hydrophilic statins.


Breast Neoplasms , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Breast Neoplasms/therapy , Denosumab/adverse effects , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Postmenopause , Prospective Studies , Retrospective Studies
3.
ESMO Open ; 6(4): 100228, 2021 08.
Article En | MEDLINE | ID: mdl-34371382

BACKGROUND: The purpose of this study was to assess the concordance of real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection of ESR1, PGR, ERBB2, and MKi67 messenger RNA (mRNA) in breast cancer tissues with central immunohistochemistry (IHC) in women treated within the prospective, randomized Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6. PATIENTS AND METHODS: We evaluated ESR1, PGR, ERBB2, and MKi67 mRNA expression by Xpert® Breast Cancer STRAT4 (enables cartridge-based RT-qPCR detection of mRNA in formalin-fixed paraffin-embedded tissues) and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 protein expression by IHC [in situ hybridization (ISH) for HER2 IHC 2+] in 1115 surgical formalin-fixed paraffin-embedded specimens from patients of ABCSG Trial 6. Overall percent agreement (concordance), positive percent agreement (sensitivity), and negative percent agreement (specificity) between STRAT4 and IHC were determined for each marker. The primary objective of the study was concordance between STRAT4 mRNA measurements of ESR1, PGR, ERBB2, and MKi67 with central reference laboratory IHC (and ISH for HER2 IHC 2+ cases). Time to distant recurrence was analyzed by Cox models. RESULTS: All performance targets for ER, PR, and Ki67 were met. For HER2, the negative percent agreement target but not the positive percent agreement target was met. Concordance between STRAT4 and IHC was 98.9% for ER, 89.9% for PR, 98.2% for HER2, and 84.8% for Ki67 (excluding intermediate IHC 10%-20% staining). In univariable and multivariable Cox regression analyses, all four biomarkers tested by either STRAT4 RT-qPCR or by central IHC (ISH) had a comparable time to distant recurrence indicating similar prognostic value. CONCLUSIONS: With the exception of HER2, we demonstrate high concordance between centrally assessed IHC and mRNA measurements of ER, PR, and Ki67 as well as a high correlation of the two methods with clinical outcome. Thus, mRNA-based assessment by STRAT4 is a promising new tool for diagnostic and therapeutic decisions in breast cancer.


Breast Neoplasms , Receptors, Progesterone , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Estrogen Receptor alpha/genetics , Female , Hormones , Humans , Ki-67 Antigen/genetics , Neoplasm Recurrence, Local , Postmenopause , Prospective Studies , RNA, Messenger/genetics , Receptor, ErbB-2 , Receptors, Progesterone/genetics
4.
Br J Surg ; 108(3): 308-314, 2021 04 05.
Article En | MEDLINE | ID: mdl-33608712

BACKGROUND: The aim of this study was to investigate whether the PAM-50-based 46-gene assay carries prognostic value for risk of local recurrence of breast cancer. METHODS: The Austrian Breast and Colorectal Cancer Study Group (ABCSG) 8 RCT compared 5 years of tamoxifen with tamoxifen for 2 years followed by anastrozole for 3 years in postmenopausal women with endocrine receptor-positive breast cancer. This study included patients from the trial who had breast-conserving surgery for whom tumour blocks were available for PAM-50 analysis. RESULTS: Tumour blocks from 1204 patients who had breast-conserving surgery were available for the PAM-50 analysis, and 1034 of these received radiotherapy. After a median follow-up of 10.8 years, 23 local events had been observed, corresponding to an overall local recurrence risk of 2.2 per cent. Univariable competing-risk analysis demonstrated that patients at low risk according to PAM-50 analysis (risk-of-recurrence (ROR) score less than 57) had a significantly lower incidence of local recurrence than those in the high-risk group at 5 years (0.1 (95 per cent c.i. 0 to 0.7) versus 2.2 (0.9 to 4.6) per cent respectively; subhazard ratio (SHR) 17.18, 95 per cent c.i. 2.06 to 142.88; P = 0.009) and 10 years (0.9 (0.4 to 2.0) versus 3.8 (1.9 to 6.6) per cent; SHR 4.76, 1.72 to 13.17; P = 0.003). Multivariable analyses that included ROR score, age, tumour size, nodal status, type of surgery, tumor grade, and trial-specific endocrine therapy confirmed that ROR score was an independent prognostic factor for risk of local recurrence. Analysis of the women randomized to radiotherapy or control after breast conservation showed that PAM-50 was not predictive of radiotherapy effect. CONCLUSION: PAM-50 can be used as a prognostic tool for local recurrence risk in postmenopausal women with hormone receptor-positive breast cancer treated with endocrine therapy. The test was not predictive for the benefit of radiotherapy.


Breast Neoplasms/genetics , Breast Neoplasms/pathology , Gene Expression Profiling/methods , Neoplasm Recurrence, Local/genetics , Age Factors , Aged , Anastrozole/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/therapy , Chemotherapy, Adjuvant , Female , Humans , Lymph Nodes/pathology , Mastectomy, Segmental , Neoplasm Grading , Postmenopause , Prognosis , Radiotherapy, Adjuvant , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Tamoxifen/therapeutic use
5.
BMC Cancer ; 20(1): 392, 2020 May 06.
Article En | MEDLINE | ID: mdl-32375735

BACKGROUND: The ABCSG-28 trial compared primary surgery followed by systemic therapy versus primary systemic therapy without surgery in patients with de novo stage IV BC. The present report describes QoL results of this trial. METHODS: Ninety patients with primary operable MBC were randomised to surgery of the primary tumor followed by systemic therapy or to primary systemic therapy without surgery. QoL analyses covering the results at baseline, 6,12,18 and 24 months follow up of 79 (88%) patients, was assessed with the EORTC QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: There were no statistically significant differences in any of the scales of the QLQ-C30 and QLQ-BR23 questionnaires between the two groups over the time. Baseline global health status and physical functioning were predictors for OS (patients with a higher score lived longer (p=0.0250, p=0.0225; p=0.0355, p=0.0355)). Global health status, social functioning scale, breast symptoms and future perspective were predictors for longer TTPd (p=0.0244; p=0.0140, p=0.020; p=0.0438, p=0.0123). Patients in both arms reported significant improvement on the emotional functioning scale. Cognitive functioning decreased over time in both groups. Younger women had clinically relevant better physical and sexual functioning scores (p=0.039 and 0.024). CONCLUSION: Primary surgery does not improve nor alter QoL of patients with de novo stage IV BC. Global health status and physical functioning were predictors for OS and could be use as additional marker for prediction of OS and TTTd in patients with de novo stage IV BC. TRIAL REGISTRATION: The trial is registered on clinicaltrial.gov (NCT01015625, date of registration:18/11/2009).


Breast Neoplasms/surgery , Mastectomy/mortality , Patient Reported Outcome Measures , Quality of Life , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Prognosis , Prospective Studies , Survival Rate , Young Adult
6.
Lasers Med Sci ; 31(2): 335-42, 2016 Feb.
Article En | MEDLINE | ID: mdl-26754179

The aim of the study was to assess the antibacterial efficacy of photon-initiated photoacoustic streaming (PIPS) using an Er:YAG laser and sonic-activated irrigation combined with QMiX irrigant or sodium hypochlorite against Enterococcus faecalis intracanal biofilm. Root canals of 91 human extracted single-canal teeth were instrumented, sterilized, contaminated with E. faecalis and incubated for 15 days. The infected teeth were then randomly distributed into six experimental groups: G1: PIPS/Er:YAG laser (wavelength 2940 nm, pulse energy 20 mJ, 15 Hz, pulse duration 50 µs, energy density 2.06 J/cm(2), 3 × 20 s) with the QMiX irrigant; G2: PIPS/Er:YAG laser-activated 2.5 % NaOCl; G3 sonic-activated irrigation (EndoActivator system) for 60 s with the QMiX irrigant; G4 sonic-activated irrigation for 60 s with 2.5 % NaOCl; G5 30-gauge needle irrigation with the QMiX irrigant; G6 30-gauge needle irrigation with 2.5 % NaOCl. The positive control group was rinsed with sterile saline solution. The root canals were sampled by flushing with saline solution at baseline and after the treatments, serially diluted and cultured. The number of bacteria in each canal was determined by plate count. The presence and the absence of E. faecalis in root canals were demonstrated by polymerase chain reaction (PCR), and the pattern of the bacteria colonization was visualized by scanning electron microscopy. There was significant reduction in the bacterial population for all groups (p < 0.001). The best antibacterial efficacy was recorded after sonic-activated irrigation with both NaOCl (99.999 %) and QMiX (99.999 %) and after PIPS with QMiX (99.999 %), which were more effective than conventional irrigation with NaOCl (99.998 %) and the PIPS with the NaOCl (99.966 %). Also, the PIPS with QMiX solution provided the highest number of sterile samples (five). There was no difference in the bacteria reduction between the active irrigation techniques, regardless of the irrigant used. Although the laser activation did not improve the antimicrobial action of the NaOCl nor QMiX, the fact that it generated the greatest number of sterile samples warrants further investigation.


Biguanides/pharmacology , Biofilms/drug effects , Dental Pulp Cavity/microbiology , Enterococcus faecalis/physiology , Photons , Polymers/pharmacology , Sodium Hypochlorite/pharmacology , Ultrasonic Waves , Biofilms/radiation effects , Drug Interactions , Enterococcus faecalis/drug effects , Enterococcus faecalis/radiation effects , Humans , Lasers, Solid-State , Root Canal Irrigants/pharmacology , Solutions
7.
SD, Rev. med. int. Síndr. Down (Ed. castell.) ; 19(3): 36-42, sept.-dic. 2015. tab, graf
Article Es | IBECS | ID: ibc-146430

Introducción. Los trastornos musculoesqueléticos a nivel del pie son frecuentes en las personas con síndrome de Down (SD). Por ello el diagnóstico precoz mediante examen podológico de las huellas plantares puede ayudar a prevenir las manifestaciones ortopédicas. El objetivo es analizar, medir y clasificar la huella plantar mediante los índices podológicos (gold standard) en jóvenes con SD. Método. Estudio transversal comparativo; se analizaron 86 huellas plantares correspondientes a 2 grupos: 21 sujetos sin SD, 11 hombres de 20,45 (2,16) años y 10 mujeres de 20 (1,70) años; y 22 sujetos con SD, 11 hombres de 23,82 (3,12) años y 11 mujeres de 24,82 (6,81) años. Se registraron las huellas plantares en bipedestación estática mediante la utilización de un podoscopio óptico y una cámara digital. Los índices analizados son Hernández-Corvo, Chippaux-Smirak, Stahelli y ángulo de Clarke. Se compararon los resultados de ambas muestras y se analizó la concordancia entre los tipos de pies, derecho e izquierdo, mediante la prueba de Chi-cuadrado. Resultados. Los sujetos con SD se clasifican con pie plano y pronador en un 38,6% según el índice de Hernández-Corvo; Chippaux-Smirak 50%; Stahelli 70,4%; y ángulo de Clarke 59,1%. Los sujetos control presentan pies cavos en un 57,1% según el índice de Hernández-Corvo; Chippaux-Smirak 59,5%; Stahelli 81%; y como pie normal según el ángulo de Clarke en un 57,1%. Hay diferencia significativa (p < 0,01) en los índices Chippaux-Smirak, Stahelli y el ángulo de Clarke. La concordancia entre pie derecho e izquierdo no fue significativa. Conclusión. Los jóvenes con SD presentan más porcentaje de pie plano pronador y menos cavos que el grupo control (AU)


Introduction: Musculoskeletal disorders of the locomotive apparatus are common in young people with Down syndrome (DS), especially in the feet. Early diagnosis by examination of podiatric footprints can help prevent orthopaedic symptoms. Our objective was to analyze, measure and classify footprints on the basis of podiatric indices (gold standard) in young people with DS. Method: Cross-sectional study; 86 footprints were analyzed from 2 groups; there were 21 healthy subjects, 11 men 20.45 (2.16) years and 10 females 20.00 (1.70) years; and 22 subjects with DS, 11 men 23.82 (3.12) years and 11 females 24.82 (6.81) years. Footprints were recorded in standing position using an optical pedoscope and a digital camera system. We calculated the Hernández-Corvo index, Chippaux-Smirak index, Clarke’s angle and Stahelli index. We then compared the results of both samples and analyzed the concordance between types of feet and right and left feet by Chi-square test. Results: Footprints in individuals with DS showed flatfoot and/or pronated foot of 38.6% according to Hernández-Corvo index; 50%, to Chippaux-Smirak; 70.4%, to Stahelli; and 59.1%, to Clarke’s angle. In healthy subjects the rates of cavus foot were 57.1%, according to Hernández- Corvo index; 59.5%, to Chippaux-Smirak index; and 81%, to Stahelli index; while 57.1% showed a normal foot based on Clarke’s angle. Differences between the 2 groups were statistically significant (P < .01) in Chippaux-Smirak index, Stahelli index and Clarke’s angle. The correlation between the right and left foot was not significant. Conclusions: Young people with DS had a higher percentage of pronation and a lower percentage of cavus foot than the control group (AU)


Adult , Female , Humans , Male , Dermatoglyphics , Down Syndrome/complications , Down Syndrome/diagnosis , Musculoskeletal Physiological Phenomena , Musculoskeletal Physiological Phenomena , Flatfoot/classification , Flatfoot/complications , Flatfoot/diagnosis , Early Diagnosis , Pronation/physiology , Cross-Sectional Studies/instrumentation , Cross-Sectional Studies/methods , Cross-Sectional Studies/trends , Podiatry/instrumentation , Podiatry/trends , Foot Diseases/complications , Foot Diseases/diagnosis
8.
Ann Oncol ; 26(8): 1685-91, 2015 Aug.
Article En | MEDLINE | ID: mdl-25935792

BACKGROUND: In the adjuvant treatment of hormone receptor-positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterization of individuals' metastasis risk are needed to reduce overtreatment. PATIENTS AND METHODS: Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests. RESULTS: At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) of 543 node-positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P < 0.0001) and 2-3N+ patients (P = 0.0002). Ten-year distant recurrence risk was significantly increased in the high-risk compared with the low-risk group derived from ROR score for 1N+ [25.5%, 95% confidence interval (CI) 17.5% to 36.1%versus 6.6%, 95% CI 3.3% to 12.8%] and compared with the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5% to 43.8% versus 12.5%, 95% CI 6.6% to 22.8%). Additionally, the luminal A intrinsic subtype (IS) exhibited significantly lower risk of distant recurrence compared with the luminal B subtype in 1N+ and 2-3N+ patients. CONCLUSION: PAM50 ROR score and IS can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment of node-positive early-stage breast cancer patients.


Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Lymph Nodes/pathology , Neoplasm Recurrence, Local , Nitriles/therapeutic use , Tamoxifen/therapeutic use , Triazoles/therapeutic use , Anastrozole , Breast Neoplasms/classification , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , Neoplasm Staging , Postmenopause , Prognosis , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Risk Assessment
9.
Ann Oncol ; 26(2): 313-20, 2015 Feb.
Article En | MEDLINE | ID: mdl-25403582

BACKGROUND: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. PATIENTS AND METHODS: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. RESULTS: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. CONCLUSION: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. CLINICALTRIALSGOV: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Density Conservation Agents/administration & dosage , Breast Neoplasms/drug therapy , Adult , Anastrozole , Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/mortality , Diphosphonates/administration & dosage , Disease-Free Survival , Female , Follow-Up Studies , Goserelin/administration & dosage , Humans , Imidazoles/administration & dosage , Kaplan-Meier Estimate , Middle Aged , Nitriles/administration & dosage , Premenopause , Tamoxifen/administration & dosage , Triazoles/administration & dosage , Zoledronic Acid
10.
Ann Oncol ; 25(2): 339-45, 2014 Feb.
Article En | MEDLINE | ID: mdl-24347518

BACKGROUND: PAM50 is a 50-gene test that is designed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been developed to be carried out in qualified routine hospital pathology laboratories. PATIENTS AND METHODS: One thousand four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial were entered into this study. Patients did not receive adjuvant chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50 test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR score were calculated. The primary analysis was designed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables. RESULTS: In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P<0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B (P<0.0001). Significant and clinically relevant discrimination between low- and high-risk groups occurred also within all tested subgroups. CONCLUSION(S): The results of the primary analysis, in combination with recently published results from the ATAC trial, constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A 10-year metastasis risk of <3.5% in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome-this finding could help to avoid unwarranted overtreatment. CLINICAL TRIAL NUMBER: ABCSG 8: NCT00291759.


Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/pathology , Neoplasm Recurrence, Local/prevention & control , Adult , Aged , Anastrozole , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Clinical Trials as Topic , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Nitriles/therapeutic use , Postmenopause , Prognosis , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Retrospective Studies , Risk , Risk Assessment , Tamoxifen/therapeutic use , Transcriptome , Treatment Outcome , Triazoles/therapeutic use
11.
Br J Cancer ; 109(3): 589-96, 2013 Aug 06.
Article En | MEDLINE | ID: mdl-23868011

BACKGROUND: We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment. METHODS: The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety. RESULTS: In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07). CONCLUSION: Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.


Aromatase Inhibitors/administration & dosage , Body Mass Index , Breast Neoplasms/drug therapy , Neoplasms, Hormone-Dependent/drug therapy , Nitriles/administration & dosage , Triazoles/administration & dosage , Adolescent , Adult , Anastrozole , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Aromatase Inhibitors/adverse effects , Chemotherapy, Adjuvant , Drug Administration Schedule , Female , Humans , Middle Aged , Nitriles/adverse effects , Obesity/physiopathology , Overweight/physiopathology , Postmenopause , Retrospective Studies , Triazoles/adverse effects , Young Adult
12.
Clin Biochem ; 46(15): 1585-9, 2013 Oct.
Article En | MEDLINE | ID: mdl-23792261

OBJECTIVES: To date, no reliable markers are available to predict response to or to assess prognosis after preoperative systemic chemotherapy (PST) in patients with locally advanced breast cancer. Previous studies demonstrated that elevated levels of soluble E-cadherin (sE-cadherin), a product of proteolytic cleavage of cell surface E-cadherin, are associated with higher risk for metastatic disease and poor prognosis in various tumor types. We, therefore, hypothesized that serum sE-cadherin levels measured before PST may correlate with pathological response. DESIGN AND METHODS: In a retrospective analysis, sE-cadherin levels were measured in sera of 108 female patients with histologically proven breast cancer before initiation of PST by using a commercially available quantitative sandwich enzyme immunoassay technique. Patients received a median number of 4 (range 3-6) cycles of anthracyline-based chemotherapy. The median patient age was 51.5 (range 21-71) years. Tumor size was measured clinically and translated into the tumor-node-metastasis (TNM)-system before the start of chemotherapy. Histopathological response in surgically removed specimens was evaluated using a modified Sinn regression score. In univariate analyses the correlations between levels of sE-cadherin and pathological response to PST were calculated. RESULTS: The histopathological regression scores correlated significantly with tumor grading (p=0.045), clinical lymph node status before PST (p=0.031) and sE-cadherin levels (p=0.039). No correlation was seen between histopathological regression scores and hormone receptor and menopausal status as well as Her2-neu status. CONCLUSION: sE-cadherin may be a marker predicting response to PST for patients with breast cancer. Our findings warrant further evaluation of sE-cadherin in a prospective trial.


Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Cadherins/genetics , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Lobular/diagnosis , Adult , Aged , Analysis of Variance , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cadherins/blood , Carcinoma, Ductal, Breast/blood , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/genetics , Carcinoma, Lobular/blood , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/genetics , Chemotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Prognosis , Proteolysis , Receptor, ErbB-2/blood , Receptor, ErbB-2/genetics , Retrospective Studies , Solubility , Tumor Burden
13.
Br J Cancer ; 108(7): 1408-14, 2013 Apr 16.
Article En | MEDLINE | ID: mdl-23511562

BACKGROUND: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. METHODS: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m(-)(2)), overweight (BMI=25-29.9 kg m(-)(2)), and obese (30 kg m(-)(2)) according to WHO criteria. RESULTS: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. CONCLUSION: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Overweight/physiopathology , Tamoxifen/therapeutic use , Aged , Aged, 80 and over , Aminoglutethimide/administration & dosage , Aminoglutethimide/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Body Mass Index , Breast Neoplasms/metabolism , Breast Neoplasms/physiopathology , Female , Humans , Middle Aged , Postmenopause , Prospective Studies , Receptors, Cell Surface/biosynthesis , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Treatment Outcome
15.
Scand J Med Sci Sports ; 20(5): 716-24, 2010 Oct.
Article En | MEDLINE | ID: mdl-20456681

Physical fitness is related to health at all ages. Information about physical fitness in the Down syndrome (DS) population, however, is scarce, especially when we consider children and adolescents. A review of the current data available on this topic would be both timely and important as it would serve as a starting point to stimulate new research perspectives. The data we reviewed from the literature showed a general trend toward lower values of physical fitness parameters and worse body composition variables in children and adolescents with DS compared with the population without intellectual disability (ID) or even with the population with ID without DS. Notably, children and adolescents with DS have been described as less active or overprotected; however, these factors may not be the cause of their poor physical fitness. Many of the training programs carried out in children and adolescents with DS did not yield the desired responses, and the reasons are still unknown. The purpose of this review is to summarize the current available literature on health-related physical fitness in children and adolescents with DS, and the effect of training on these variables. From the literature available, it is clear that more data on this population are necessary.


Down Syndrome/physiopathology , Physical Education and Training , Physical Fitness/physiology , Adolescent , Body Composition , Child , Exercise/physiology , Humans , Muscle Strength
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