Browsing by Subject "Breast cancer"

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Physical activity and Mediterranean diet as potential modulators of osteoprotegerin and soluble RANKL in gBRCA1/2 mutation carriers: Results of the lifestyle intervention pilot study LIBRE-1
(2021) Neirich, Leonie; Yahiaoui-Doktor, Maryam; Lammert, Jacqueline; Basrai, Maryam; Seethaler, Benjamin; Berling-Ernst, Anika; Ramser, Juliane; Quante, Anne S.; Schmidt, Thorsten; Niederberger, Uwe; Rhiem, Kerstin; Schmutzler, Rita; Engel, Christoph; Bischoff, Stephan C.; Halle, Martin; Kiechle, Marion; Grill, Sabine
Purpose: Emerging evidence suggests that the progesterone-mediated receptor activator of nuclear factor κB (RANK)/soluble RANK ligand (sRANKL)/osteoprotegerin (OPG) pathway plays an important role in mammary carcinogenesis and is hyperactivated in germline (g)BRCA1/2 mutation carriers. We analyzed the effects of a 3-month intensive lifestyle intervention within the LIBRE-1 study on the serum levels of OPG and sRANKL and hypothesized that the intervention program provides a beneficial impact on the biomarkers by increasing OPG and reducing sRANKL serum concentrations. Methods: Serum levels of OPG and sRANKL of 49 gBRCA1/2 mutation carriers were quantified using enzyme-linked immunosorbent assays. We used previously collected blood samples from participants of the prospective LIBRE-1 study, who were randomized into an intervention group (IG), increasing physical activity and adherence to the Mediterranean diet (MedD) through supervised sessions from study entry to the first study visit after 3 months and a usual-care control group (CG). Differences in biomarker levels before and after the 3-month intervention were tested within and between study groups. Results: The lifestyle intervention resulted in a significant increase in OPG for participants in both the IG (q = 0.022) and CG (q = 0.002). sRANKL decreased significantly in the IG (q = 0.0464) and seemed to decrease in the CG (q = 0.5584). An increase in the intake of Omega-3 polyunsaturated fatty acids was significantly associated with an increase in OPG (r = 0.579, q = 0.045). Baseline serum levels of sRANKL were a strong predictor for the change of sRANKL in the course of the intervention (ß-estimate = − 0.70; q = 0.0018). Baseline physical fitness (assessed as VO2peak) might predict the change of OPG in the course of the intervention program (ß-estimate = 0.133 pg/ml/ml/min/kg; p = 0.0319; q = 0.2871). Conclusion: Findings from this pilot study seem to confirm our hypothesis by showing an increase in OPG and decrease in sRANKL over a 3-month lifestyle intervention and suggest that increased physical activity and adherence to the MedD are potent modulators of the biomarkers OPG and potentially sRANKL.
Precursor fractions of neurotensin and enkephalin might point to molecular mechanisms of cancer risk modulation during a lifestyle-intervention in germline BRCA1/2 gene mutation carriers
(2021) Grill, Sabine; Yahiaoui-Doktor, Maryam; Basrai, Maryam; Struck, Joachim; Schulte, Janin; Berling-Ernst, Anika; Engel, Christoph; Ullrich, Mirjam; Lammert, Jacqueline; Bischoff, Stephan C.; Schmidt, Thorsten; Niederberger, Uwe; Chronas, Dimitrios; Rhiem, Kerstin; Schmutzler, Rita; Halle, Martin; Kiechle, Marion
Background: Germline BRCA1/2 mutation carriers (gBMC) face increased cancer risks that are modulated via non-genetic lifestyle factors whose underlying molecular mechanisms are unknown. The peptides Neurotensin (NT) and Enkephalin (ENK)—involved in tumorigenesis and obesity-related diseases—are of interest. We wanted to know whether these biomarkers differ between gBMC and women from the general population and what effect a 1-year lifestyle-intervention has in gBMC. Methods: The stable precursor fragments pro-NT and pro-ENK were measured at study entry (SE), after 3 and 12 months for 68 women from LIBRE-1 (a controlled lifestyle-intervention feasibility trial for gBMC involving structured endurance training and the Mediterranean Diet). The SE values were compared with a cohort of the general population including female subjects with and without previous cancer disease, non-suggestive for hereditary breast and ovarian cancer (OMA-reference). For LIBRE-1, we analysed the association between the intervention-related change in the two biomarkers and certain lifestyle factors. Results: At SE, gBMC had a higher median pro-NT than OMA-reference (in the subgroups with previous cancer 117 vs. 91 pmol/L, p = 0.002). Non-diseased gBMC had lower median pro-ENK levels when compared to the non-diseased reference group. VO2peak and pro-NT 1-year change in LIBRE-1 were inversely correlated (r = − 0.435; CI − 0.653 to − 0.151; p = 0.004). Pro-ENK correlated positively with VO2peak at SE (r = 0.323; CI 0.061–0.544; p = 0.017). Regression analyses showed an inverse association of 1-year changes for pro-NT and Omega-6/Omega-3 (Estimate: − 37.9, p = 0.097/0.080) in multivariate analysis. Conclusion: Our results give first indications for lifestyle-related modification particularly of pro-NT in gBMC.
Predictors of cardiopulmonary fitness in cancer-affected and -unaffected women with a pathogenic germline variant in the genes BRCA1/2 (LIBRE-1)
(2022) Berling-Ernst, Anika; Yahiaoui-Doktor, Maryam; Kiechle, Marion; Engel, Christoph; Lammert, Jacqueline; Grill, Sabine; Dukatz, R.; Rhiem, Kerstin; Baumann, F. T.; Bischoff, Stephan C.; Erickson, N.; Schmidt, Thorsten; Niederberger, Uwe; Siniatchkin, M.; Halle, Martin; Berling-Ernst, A.; Department of Prevention and Sports Medicine, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; Yahiaoui-Doktor, M.; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany; Kiechle, M.; Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, University Hospital Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; Engel, C.; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany; Lammert, J.; Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, University Hospital Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; Grill, S.; Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, University Hospital Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; Dukatz, R.; Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, University Hospital Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; Rhiem, K.; Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Nordrhein-Westfalen, Germany; Baumann, F. T.; Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Nordrhein-Westfalen, Germany; Bischoff, S. C.; Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany; Erickson, N.; Comprehensive Cancer Center Ludwig Maximillian University (CCC LMU), University of Munich Clinic, Munich, Germany; Schmidt, T.; University Cancer Center Schleswig-Holstein (UCCSH), Kiel, Germany; Niederberger, U.; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel, Germany; Siniatchkin, M.; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel, Germany; Halle, M.; DZHK (German Centre for Cardiovascular Research), Munich, Germany
Physical activity (PA) helps prevention and aftercare of sporadic breast cancer (BC), cardiopulmonary fitness (CPF) being an age-independent predictor of tumor-specific mortality. Therefore, we wanted to identify predictors of CPF (represented by peak oxygen uptake: VO2peak) in BRCA1/2 mutation carriers whose risk of developing BC is high. We used cross-sectional data from 68 BRCA1/2 germline mutation carrying women participating in the randomized, prospective, controlled clinical study LIBRE-1. Assessments included cardiopulmonary exercise testing, medical and lifestyle history plus socioeconomic status. Additionally, the participants completed a psychological questionnaire regarding their attitude, subjective norms, perceived behavior control and intention towards PA. A multivariate logistic regression model was used to identify predictors for participants reaching their age- and sex-adjusted VO2peak reference values. 22 participants (median age: 40 years, interquartile range (IQR) 33–46) were cancer-unaffected and 46 cancer-affected (median age: 44 years, IQR 35–50). The strongest predictor for reaching the reference VO2peak value was attitude towards PA (Odds Ratio 3.0; 95% Confidence Interval 1.3–8.4; p = 0.021). None of the other predictors showed a significant association. A positive attitude towards PA seems to be associated with VO2peak, which should be considered in developing therapeutic and preventive strategies.Trial registrations: NCT02087592; DRKS00005736.