@article{ThibaudeauTaubenbergerHolzapfeletal.2014,
  author    = {Thibaudeau, Laure and Taubenberger, Anna V. and Holzapfel, Boris M. and Quent, Verena M. and Fuehrmann, Tobias and Hesami, Parisa and Brown, Toby D. and Dalton, Paul D. and Power, Carl A. and Hollier, Brett G. and Hutmacher, Dietmar W.},
  title     = {A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone},
  series = {Disease Models \& Mechanisms},
  volume    = {7},
  journal   = {Disease Models \& Mechanisms},
  number    = {2},
  doi       = {10.1242/dmm.014076},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117466},
  pages     = {299-309},
  year      = {2014},
  abstract  = {The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact 'organ' bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo.},
  language  = {en}
}
@article{TelesYanoVillarinhoetal.2021,
  author    = {Teles, Ramon Handerson Gomes and Yano, Rafael Sussumu and Villarinho, Nicolas Jones and Yamagata, Ana Sayuri and Jaeger, Ruy Gastaldoni and Meybohm, Patrick and Burek, Malgorzata and Freitas, Vanessa Morais},
  title     = {Advances in breast cancer management and extracellular vesicle research, a bibliometric analysis},
  series = {Current Oncology},
  volume    = {28},
  journal   = {Current Oncology},
  number    = {6},
  issn      = {1718-7729},
  doi       = {10.3390/curroncol28060382},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284321},
  pages     = {4504 -- 4520},
  year      = {2021},
  abstract  = {Extracellular vesicles transport variable content and have crucial functions in cell-cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, we aimed to investigate the trends in breast cancer management involved with extracellular vesicle research. Articles were retrieved from Scopus, including all the documents published concerning breast cancer and extracellular vesicles. We analyzed authors, journals, citations, affiliations, and keywords, besides other bibliometric analyses, using R Studio version 3.6.2. and VOSviewer version 1.6.0. A total of 1151 articles were retrieved, and as the main result, our analysis revealed trending topics on biomarkers of liquid biopsy, drug delivery, chemotherapy, autophagy, and microRNA. Additionally, research related to extracellular vesicles in breast cancer has been focused on diagnosis, treatment, and mechanisms of action of breast tumor-derived vesicles. Future studies are expected to explore the role of extracellular vesicles on autophagy and microRNA, besides investigating the application of extracellular vesicles from liquid biopsies for biomarkers and drug delivery, enabling the development and validation of therapeutic strategies for specific cancers.},
  language  = {en}
}
@article{AnStrisselAlAbboodietal.2022,
  author    = {An, Ran and Strissel, Pamela L. and Al-Abboodi, Majida and Robering, Jan W. and Supachai, Reakasame and Eckstein, Markus and Peddi, Ajay and Hauck, Theresa and B{\"a}uerle, Tobias and Boccaccini, Aldo R. and Youssef, Almoatazbellah and Sun, Jiaming and Strick, Reiner and Horch, Raymund E. and Boos, Anja M. and Kengelbach-Weigand, Annika},
  title     = {An innovative arteriovenous (AV) loop breast cancer model tailored for cancer research},
  series = {Bioengineering},
  volume    = {9},
  journal   = {Bioengineering},
  number    = {7},
  issn      = {2306-5354},
  doi       = {10.3390/bioengineering9070280},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278919},
  year      = {2022},
  abstract  = {Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate-fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.},
  language  = {en}
}
@article{CurtazReifschlaegerStraehleetal.2022,
  author    = {Curtaz, Carolin J. and Reifschl{\"a}ger, Leonie and Str{\"a}hle, Linus and Feldheim, Jonas and Feldheim, Julia J. and Schmitt, Constanze and Kiesel, Matthias and Herbert, Saskia-Laureen and W{\"o}ckel, Achim and Meybohm, Patrick and Burek, Malgorzata},
  title     = {Analysis of microRNAs in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073683},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284476},
  year      = {2022},
  abstract  = {Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.},
  language  = {en}
}
@article{CurtazKieselMeybohmetal.2022,
  author    = {Curtaz, Carolin J. and Kiesel, Ludwig and Meybohm, Patrick and W{\"o}ckel, Achim and Burek, Malgorzata},
  title     = {Anti-hormonal therapy in breast cancer and its effect on the blood-brain barrier},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14205132},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290320},
  year      = {2022},
  abstract  = {Simple Summary Anti-hormonal therapie regimes are well established in oncological treatments in breast cancer. In contrast there is limited knowledge of their effects on metastatic brain metastases in advanced breast cancer and their ability to cross the blood brain-barrier. In this review, we point out the usual antihormonal therapy options in the primary disease, but also in metastatic breast cancer. In addition, we explain the epidemiological facts of brain metastases, as well as the basics of the blood-brain barrier and how this is overcome by metastase. Last but not least, we deal with the known anti-hormonal therapy options and present clinical studies on their intracerebral effect, as well as the known basics of their blood-brain barrier penetration. Not all common anti-hormonal therapeutics are able to penetrate the CNS. It is therefore important for the treating oncologists to use substances that have been proven to cross the BBB, despite the limited data available. Aromataseinhibitors, especially letrozole, probably also tamoxifen, everolimus and CDK4/6 inhibitors, especially abemaciclib, appear to act intracerebrally by overcoming the blood-brain barrier. Nevertheless, further data must be obtained in basic research, but also health care research in relation to patients with brain metastases. Abstract The molecular receptor status of breast cancer has implications for prognosis and long-term metastasis. Although metastatic luminal B-like, hormone-receptor-positive, HER2-negative, breast cancer causes brain metastases less frequently than other subtypes, though tumor metastases in the brain are increasingly being detected of this patient group. Despite the many years of tried and tested use of a wide variety of anti-hormonal therapeutic agents, there is insufficient data on their intracerebral effectiveness and their ability to cross the blood-brain barrier. In this review, we therefore summarize the current state of knowledge on anti-hormonal therapy and its intracerebral impact and effects on the blood-brain barrier in breast cancer.},
  language  = {en}
}
@article{VargasCasanovaRodriguezGuerraUmanaPerezetal.2017,
  author    = {Vargas Casanova, Yerly and Rodr{\´i}guez Guerra, Jorge Antonio and Uma{\~n}a P{\´e}rez, Yadi Adriana and Leal Castro, Aura Luc{\´i}a and Almanzar Reina, Giovanni and Garc{\´i}a Casta{\~n}eda, Javier Eduardo and Rivera Monroy, Zuly Jenny},
  title     = {Antibacterial synthetic peptides derived from bovine lactoferricin exhibit cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines},
  series = {Molecules},
  volume    = {22},
  journal   = {Molecules},
  number    = {10},
  doi       = {10.3390/molecules22101641},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173887},
  year      = {2017},
  abstract  = {Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)\(_2\)K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.},
  language  = {en}
}
@article{BartmannJanakiRamanFloeteretal.2018,
  author    = {Bartmann, Catharina and Janaki Raman, Sudha R. and Fl{\"o}ter, Jessica and Schulze, Almut and Bahlke, Katrin and Willingstorfer, Jana and Strunz, Maria and W{\"o}ckel, Achim and Klement, Rainer J. and Kapp, Michaela and Djuzenova, Cholpon S. and Otto, Christoph and K{\"a}mmerer, Ulrike},
  title     = {Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation},
  series = {Cancer \& Metabolism},
  volume    = {6},
  journal   = {Cancer \& Metabolism},
  number    = {8},
  doi       = {10.1186/s40170-018-0180-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175607},
  year      = {2018},
  abstract  = {Background: Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Therefore, we investigated the effect of a physiological concentration of 3 mM 3-OHB on metabolism, proliferation, and viability of breast cancer (BC) cells in vitro. Methods: Seven different human BC cell lines (BT20, BT474, HBL100, MCF-7, MDA-MB 231, MDA-MB 468, and T47D) were cultured in medium with 5 mM glucose in the presence of 3 mM 3-OHB at mild hypoxia (5\% oxygen) or normoxia (21\% oxygen). Metabolic profiling was performed by quantification of the turnover of glucose, lactate, and 3-OHB and by Seahorse metabolic flux analysis. Expression of key enzymes of ketolysis as well as the main monocarboxylic acid transporter MCT2 and the glucose-transporter GLUT1 was analyzed by RT-qPCR and Western blotting. The effect of 3-OHB on short- and long-term cell proliferation as well as chemo- and radiosensitivity were also analyzed. Results: 3-OHB significantly changed the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in BT20 cells resulting in a more oxidative energetic phenotype. MCF-7 and MDA-MB 468 cells had increased ECAR only in response to 3-OHB, while the other three cell types remained uninfluenced. All cells expressed MCT2 and GLUT1, thus being able to uptake the metabolites. The consumption of 3-OHB was not strongly linked to mRNA overexpression of key enzymes of ketolysis and did not correlate with lactate production and glucose consumption. Neither 3-OHB nor acetoacetate did interfere with proliferation. Further, 3-OHB incubation did not modify the response of the tested BC cell lines to chemotherapy or radiation. Conclusions: We found that a physiological level of 3-OHB can change the energetic profile of some BC cell lines. However, 3-OHB failed to influence different biologic processes in these cells, e.g., cell proliferation and the response to common breast cancer chemotherapy and radiotherapy. Thus, we have no evidence that 3-OHB generally influences the biology of breast cancer cells in vitro.},
  language  = {en}
}
@article{WielandStrisselSchorleetal.2021,
  author    = {Wieland, Annalena and Strissel, Pamela L. and Schorle, Hannah and Bakirci, Ezgi and Janzen, Dieter and Beckmann, Matthias W. and Eckstein, Markus and Dalton, Paul D. and Strick, Reiner},
  title     = {Brain and breast cancer cells with PTEN loss of function reveal enhanced durotaxis and RHOB dependent amoeboid migration utilizing 3D scaffolds and aligned microfiber tracts},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13205144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248443},
  year      = {2021},
  abstract  = {Background: Glioblastoma multiforme (GBM) and metastatic triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with poor patient outcome, thus new therapeutic targets are needed. To understand signaling, controlling the dynamics and mechanics of brain tumor cell migration, we implemented GBM and TNBC cell lines and designed 3D aligned microfibers and scaffolds mimicking brain structures. Methods: 3D microfibers and scaffolds were printed using melt electrowriting. GBM and TNBC cell lines with opposing PTEN genotypes were analyzed with RHO-ROCK-PTEN inhibitors and PTEN rescue using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while scanning electron microscopy and confocal microscopy addressed cell morphology. Results: In contrast to the PTEN wildtype, GBM and TNBC cells with PTEN loss of function yielded enhanced durotaxis, topotaxis, adhesion, amoeboid migration on 3D microfibers and significant high RHOB expression. Functional studies concerning RHOB-ROCK-PTEN signaling confirmed the essential role for the above cellular processes. Conclusions: This study demonstrates a significant role of the PTEN genotype and RHOB expression for durotaxis, adhesion and migration dependent on 3D. GBM and TNBC cells with PTEN loss of function have an affinity for stiff brain structures promoting metastasis. 3D microfibers represent an important tool to model brain metastasizing tumor cells, where RHO-inhibitors could play an essential role for improved therapy.},
  language  = {en}
}
@article{ReinersSchneiderPlatonovaetal.2020,
  author    = {Reiners, Christoph and Schneider, Rita and Platonova, Tamara and Fridman, Mikhail and Malzahn, Uwe and M{\"a}der, Uwe and Vrachimis, Alexis and Bogdanova, Tatiana and Krajewska, Jolanta and Elisei, Rossella and Vaisman, Fernanda and Mihailovic, Jasna and Costa, Gracinda and Drozd, Valentina},
  title     = {Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey},
  series = {Frontiers in Endocrinology},
  volume    = {11},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2020.00381},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207766},
  year      = {2020},
  abstract  = {Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case-control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2\%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10\% false-positivity rate which potentially produced substantial "misdiagnosis."},
  language  = {en}
}
@article{WischnewskySchwentnerDiessneretal.2021,
  author    = {Wischnewsky, Manfred and Schwentner, Lukas and Diessner, Joachim and De Gregorio, Amelie and Joukhadar, Ralf and Davut, Dayan and Salmen, Jessica and Bekes, Inga and Kiesel, Matthias and M{\"u}ller-Reiter, Max and Blettner, Maria and Wolters, Regine and Janni, Wolfgang and Kreienberg, Rolf and W{\"o}ckel, Achim and Ebner, Florian},
  title     = {BRENDA-Score, a hghly significant, internally and externally validated prognostic marker for metastatic recurrence: analysis of 10,449 primary breast cancer patients},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {13},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13133121},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241064},
  year      = {2021},
  abstract  = {Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95\%CI (1.7-3.3); intermediate risk: HR = 5.0, 95\%CI.(3.6-6.9); high risk: HR = 10.3, 95\%CI (7.4-14.3) and very high risk: HR = 18.1, 95\%CI (13.2-24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.},
  language  = {en}
}
@article{WeberLassalleHaukeRamseretal.2018,
  author    = {Weber-Lassalle, Nana and Hauke, Jan and Ramser, Juliane and Richters, Lisa and Groß, Eva and Bl{\"u}mcke, Britta and Gehrig, Andrea and Kahlert, Anne-Karin and M{\"u}ller, Clemens R. and Hackmann, Karl and Honisch, Ellen and Weber-Lassalle, Konstantin and Niederacher, Dieter and Borde, Julika and Thiele, Holger and Ernst, Corinna and Altm{\"u}ller, Janine and Neidhardt, Guido and N{\"u}rnberg, Peter and Klaschik, Kristina and Schroeder, Christopher and Platzer, Konrad and Volk, Alexander E. and Wang-Gohrke, Shan and Just, Walter and Auber, Bernd and Kubisch, Christian and Schmidt, Gunnar and Horvath, Judit and Wappenschmidt, Barbara and Engel, Christoph and Arnold, Norbert and Dworniczak, Bernd and Rhiem, Kerstin and Meindl, Alfons and Schmutzler, Rita K. and Hahnen, Eric},
  title     = {BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer},
  series = {Breast Cancer Research},
  volume    = {20},
  journal   = {Breast Cancer Research},
  doi       = {10.1186/s13058-018-0935-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233433},
  year      = {2018},
  abstract  = {Background Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. Methods To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. Results BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR) = 20.97, 95\% confidence interval (CI) = 12.02-36.57, P < 0.0001) and in the subgroup of index patients with late-onset OC (OR = 29.91, 95\% CI = 14.99-59.66, P < 0.0001). No significant association of BRIP1 LoF mutations with familial BC was observed (OR = 1.81 95\% CI = 1.00-3.30, P = 0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR = 1.42, 95\% CI = 0.70-2.90, P = 0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR = 3.59, 95\% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P = 0.0014) but not in BC (P = 0.0693) patients. Conclusions To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded.},
  language  = {en}
}
@article{WolterHanselmannPattschulletal.2017,
  author    = {Wolter, Patrick and Hanselmann, Steffen and Pattschull, Grit and Schruf, Eva and Gaubatz, Stefan},
  title     = {Central spindle proteins and mitotic kinesins are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cell lines and are potential targets for therapy},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {7},
  doi       = {10.18632/oncotarget.14466},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171851},
  pages     = {11160-11172},
  year      = {2017},
  abstract  = {The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1. We demonstrate that six mitotic kinesins and two microtubule-associated non-motor proteins (MAPs) CEP55 and PRC1 are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cells. Suppression of KIF23 and PRC1 strongly suppressed proliferation of MDA-MB-231 cells. The set of MMB-FOXM1 regulated kinesins genes and 4 additional kinesins which we referred to as the mitotic kinesin signature (MKS) is linked to poor outcome in breast cancer patients. Thus, mitotic kinesins could be used as prognostic biomarker and could be potential therapeutic targets for the treatment of breast cancer.},
  language  = {en}
}
@article{SchlerethHeylKrampitzetal.2013,
  author    = {Schlereth, Katharina and Heyl, Charlotte and Krampitz, Anna-Maria and Mernberger, Marco and Finkernagel, Florian and Scharfe, Maren and Jarek, Michael and Leich, Ellen and Rosenwald, Andreas and Stiewe, Thorsten},
  title     = {Characterization of the p53 Cistrome - DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions},
  series = {PLOS Genetics},
  volume    = {9},
  journal   = {PLOS Genetics},
  number    = {8},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1003726},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127579},
  pages     = {e1003726},
  year      = {2013},
  abstract  = {p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells. How p53 selects target genes in the genome in a context-and tissue-specific manner remains largely obscure. There is growing evidence that the ability of p53 to bind DNA in a cooperative manner prominently influences target gene selection with activation of the apoptosis program being completely dependent on DNA binding cooperativity. Here, we used ChIP-seq to comprehensively profile the cistrome of p53 mutants with reduced or increased cooperativity. The analysis highlighted a particular relevance of cooperativity for extending the p53 cistrome to non-canonical binding sequences characterized by deletions, spacer insertions and base mismatches. Furthermore, it revealed a striking functional separation of the cistrome on the basis of cooperativity; with low cooperativity genes being significantly enriched for cell cycle and high cooperativity genes for apoptotic functions. Importantly, expression of high but not low cooperativity genes was correlated with superior survival in breast cancer patients. Interestingly, in contrast to most p53-activated genes, p53-repressed genes did not commonly contain p53 binding elements. Nevertheless, both the degree of gene activation and repression were cooperativity-dependent, suggesting that p53-mediated gene repression is largely indirect and mediated by cooperativity-dependently transactivated gene products such as CDKN1A, E2F7 and non-coding RNAs. Since both activation of apoptosis genes with non-canonical response elements and repression of pro-survival genes are crucial for p53's apoptotic activity, the cistrome analysis comprehensively explains why p53-induced apoptosis, but not cell cycle arrest, strongly depends on the intermolecular cooperation of p53 molecules as a possible safeguard mechanism protecting from accidental cell killing.},
  language  = {en}
}
@article{SchmidSchmidtHazuretal.2020,
  author    = {Schmid, Rafael and Schmidt, Sonja K. and Hazur, Jonas and Detsch, Rainer and Maurer, Evelyn and Boccaccini, Aldo R. and Hauptstein, Julia and Teßmar, J{\"o}rg and Blunk, Torsten and Schr{\"u}fer, Stefan and Schubert, Dirk W. and Horch, Raymund E. and Bosserhoff, Anja K. and Arkudas, Andreas and Kengelbach-Weigand, Annika},
  title     = {Comparison of hydrogels for the development of well-defined 3D cancer models of breast cancer and melanoma},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {8},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12082320},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211195},
  year      = {2020},
  abstract  = {Bioprinting offers the opportunity to fabricate precise 3D tumor models to study tumor pathophysiology and progression. However, the choice of the bioink used is important. In this study, cell behavior was studied in three mechanically and biologically different hydrogels (alginate, alginate dialdehyde crosslinked with gelatin (ADA-GEL), and thiol-modified hyaluronan (HA-SH crosslinked with PEGDA)) with cells from breast cancer (MDA-MB-231 and MCF-7) and melanoma (Mel Im and MV3), by analyzing survival, growth, and the amount of metabolically active, living cells via WST-8 labeling. Material characteristics were analyzed by dynamic mechanical analysis. Cell lines revealed significantly increased cell numbers in low-percentage alginate and HA-SH from day 1 to 14, while only Mel Im also revealed an increase in ADA-GEL. MCF-7 showed a preference for 1\% alginate. Melanoma cells tended to proliferate better in ADA-GEL and HA-SH than mammary carcinoma cells. In 1\% alginate, breast cancer cells showed equally good proliferation compared to melanoma cell lines. A smaller area was colonized in high-percentage alginate-based hydrogels. Moreover, 3\% alginate was the stiffest material, and 2.5\% ADA-GEL was the softest material. The other hydrogels were in the same range in between. Therefore, cellular responses were not only stiffness-dependent. With 1\% alginate and HA-SH, we identified matrices that enable proliferation of all tested tumor cell lines while maintaining expected tumor heterogeneity. By adapting hydrogels, differences could be accentuated. This opens up the possibility of understanding and analyzing tumor heterogeneity by biofabrication.},
  language  = {en}
}
@article{StanglRauchRauhetal.2021,
  author    = {Stangl, Stephanie and Rauch, Sebastian and Rauh, J{\"u}rgen and Meyer, Martin and M{\"u}ller-Nordhorn, Jacqueline and Wildner, Manfred and W{\"o}ckel, Achim and Heuschmann, Peter U.},
  title     = {Disparities in Accessibility to Evidence-Based Breast Cancer Care Facilities by Rural and Urban Areas in Bavaria, Germany},
  series = {Cancer},
  volume    = {127},
  journal   = {Cancer},
  number    = {13},
  doi       = {10.1002/cncr.33493},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239854},
  pages     = {2319 -- 2332},
  year      = {2021},
  abstract  = {Background Breast cancer (BC), which is most common in elderly women, requires a multidisciplinary and continuous approach to care. With demographic changes, the number of patients with chronic diseases such as BC will increase. This trend will especially hit rural areas, where the majority of the elderly live, in terms of comprehensive health care. Methods Accessibility to several cancer facilities in Bavaria, Germany, was analyzed with a geographic information system. Facilities were identified from the national BC guideline and from 31 participants in a proof-of-concept study from the Breast Cancer Care for Patients With Metastatic Disease registry. The timeframe for accessibility was defined as 30 or 60 minutes for all population points. The collection of address information was performed with different sources (eg, a physician registry). Routine data from the German Census 2011 and the population-based Cancer Registry of Bavaria were linked at the district level. Results Females from urban areas (n = 2,938,991 [ie, total of females living in urban areas]) had a higher chance for predefined accessibility to the majority of analyzed facilities in comparison with females from rural areas (n = 3,385,813 [ie, total number of females living in rural areas]) with an odds ratio (OR) of 9.0 for cancer information counselling, an OR of 17.2 for a university hospital, and an OR of 7.2 for a psycho-oncologist. For (inpatient) rehabilitation centers (OR, 0.2) and genetic counselling (OR, 0.3), women from urban areas had lower odds of accessibility within 30 or 60 minutes. Conclusions Disparities in accessibility between rural and urban areas exist in Bavaria. The identification of underserved areas can help to inform policymakers about disparities in comprehensive health care. Future strategies are needed to deliver high-quality health care to all inhabitants, regardless of residence.},
  language  = {en}
}
@article{HarterBernatzScholzetal.2015,
  author    = {Harter, Patrick N. and Bernatz, Simon and Scholz, Alexander and Zeiner, Pia S. and Zinke, Jenny and Kiyose, Makoto and Blasel, Stella and Beschorner, Rudi and Senft, Christian and Bender, Benjamin and Ronellenfitsch, Michael W. and Wikman, Harriet and Glatzel, Markus and Meinhardt, Matthias and Juratli, Tareq A. and Steinbach, Joachim P. and Plate, Karl H. and Wischhusen, J{\"o}rg and Weide, Benjamin and Mittelbronn, Michel},
  title     = {Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases},
  series = {Oncotarget},
  volume    = {6},
  journal   = {Oncotarget},
  number    = {38},
  doi       = {10.18632/oncotarget.5696},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137107},
  pages     = {40836 -- 40849},
  year      = {2015},
  abstract  = {The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.},
  language  = {en}
}
@article{OsorioMilneKuchenbaeckeretal.2014,
  author    = {Osorio, Ana and Milne, Roger L. and Kuchenbaecker, Karoline and Vaclov{\´a}, Tereza and Pita, Guillermo and Alonso, Rosario and Peterlongo, Paolo and Blanco, Ignacio and de la Hoya, Miguel and Duran, Mercedes and Diez, Orland and Ram{\´o}n y Cajal, Teresa and Konstantopoulou, Irene and Mart{\´i}nez-Bouzas, Christina and Conejero, Raquel Andr{\´e}s and Soucy, Penny and McGuffog, Lesley and Barrowdale, Daniel and Lee, Andrew and Arver, Brita and Rantala, Johanna and Loman, Niklas and Ehrencrona, Hans and Olopade, Olufunmilayo I. and Beattie, Mary S. and Domchek, Susan M. and Nathanson, Katherine and Rebbeck, Timothy R. and Arun, Banu K. and Karlan, Beth Y. and Walsh, Christine and Lester, Jenny and John, Esther M. and Whittemore, Alice S. and Daly, Mary B. and Southey, Melissa and Hopper, John and Terry, Mary B. and Buys, Saundra S. and Janavicius, Ramunas and Dorfling, Cecilia M. and van Rensburg, Elizabeth J. and Steele, Linda and Neuhausen, Susan L. and Ding, Yuan Chun and Hansen, Thomas V. O. and J{\o}nson, Lars and Ejlertsen, Bent and Gerdes, Anne-Marie and Infante, Mar and Herr{\´a}ez, Bel{\´e}n and Moreno, Leticia Thais and Weitzel, Jeffrey N. and Herzog, Josef and Weeman, Kisa and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Scuvera, Guilietta and Bonanni, Bernardo and Mariette, Frederique and Volorio, Sara and Viel, Alessandra and Varesco, Liliana and Papi, Laura and Ottini, Laura and Tibiletti, Maria Grazia and Radice, Paolo and Yannoukakos, Drakoulis and Garber, Judy and Ellis, Steve and Frost, Debra and Platte, Radka and Fineberg, Elena and Evans, Gareth and Lalloo, Fiona and Izatt, Louise and Eeles, Ros and Adlard, Julian and Davidson, Rosemarie and Cole, Trevor and Eccles, Diana and Cook, Jackie and Hodgson, Shirley and Brewer, Carole and Tischkowitz, Marc and Douglas, Fiona and Porteous, Mary and Side, Lucy and Walker, Lisa and Morrison, Patrick and Donaldson, Alan and Kennedy, John and Foo, Claire and Godwin, Andrew K. and Schmutzler, Rita Katharina and Wappenschmidt, Barbara and Rhiem, Kerstin and Engel, Christoph and Meindl, Alftons and Ditsch, Nina and Arnold, Norbert and Plendl, Hans J{\"o}rg and Niederacher, Dieter and Sutter, Christian and Wang-Gohrke, Shan and Steinemann, Doris and Preisler-Adams, Sabine and Kast, Karin and Varon-Mateeva, Raymonda and Gehrig, Andrea and Stoppa-Lyonnet, Dominique and Sinilnikova, Olga M. and Mazoyer, Sylvie and Damiola, Francesca and Poppe, Bruce and Claes, Kathleen and Piedmonte, Marion and Tucker, Kathy and Backes, Floor and Rodr{\´i}guez, Gustavo and Brewster, Wendy and Wakeley, Katie and Rutherford, Thomas and Cald{\´e}s, Trinidad and Nevanlinna, Heli and Aittom{\"a}ki, Kristiina and Rookus, Matti A. and van Os, Theo A. M. and van der Kolk, Lizet and de Lange, J. L. and Meijers-Heijboer, Hanne E. J. and van der Hout, A. H. and van Asperen, Christi J. and Gom{\´e}z Garcia, Encarna B. and Encarna, B. and Hoogerbrugge, Nicoline and Coll{\´e}e, J. Margriet and van Deurzen, Carolien H. M. and van der Luijt, Rob B. and Devilee, Peter and Olah, Edith and L{\´a}zaro, Conxi and Teul{\´e}, Alex and Men{\´e}ndez, Mireia and Jakubowska, Anna and Cybulski, Cezary and Gronwald, Jecek and Lubinski, Jan and Durda, Katarzyna and Jaworska-Bieniek, Katarzyna and Johannsson, Oskar Th. and Maugard, Christine and Montagna, Marco and Tognazzo, Silvia and Teixeira, Manuel R. and Healey, Sue and Olswold, Curtis and Guidugli, Lucia and Lindor, Noralane and Slager, Susan and Szabo, Csilla I. and Vijai, Joseph and Robson, Mark and Kauff, Noah and Zhang, Liying and Rau-Murthy, Rohini and Fink-Retter, Anneliese and Singer, Christine F. and Rappaport, Christine and Kaulich, Daphne Geschwantler and Pfeiler, Georg and Tea, Muy-Kheng and Berger, Andreas and Phelan, Catherine M. and Greene, Mark H. and Mai, Phuong L. and Lejbkowicz, Flavio and Andrulis, Irene and Mulligan, Anna Marie and Glendon, Gord and Toland, Amanda Ewart and Bojesen, Anders and Pedersen, Inge Sokilde and Sunde, Lone and Thomassen, Mads and Kruse, Torben A. and Jensen, Uffe Birk and Friedman, Eitan and Laitman, Yeal and Shimon, Shanie Paluch and Simard, Jaques and Easton, Douglas F. and Offit, Kenneth and Couch, Fergus J. and Chenevix-Trench, Georgia and Antoniou, Antonis C. and Benitez, Javier},
  title     = {DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers},
  series = {PLOS Genetics},
  volume    = {4},
  journal   = {PLOS Genetics},
  number    = {e1004256},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1004256},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116820},
  year      = {2014},
  abstract  = {Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95\% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95\% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.},
  language  = {en}
}
@article{DiessnerWischnewskyBlettneretal.2016,
  author    = {Diessner, Joachim and Wischnewsky, Manfred and Blettner, Maria and H{\"a}usler, Sebastian and Janni, Wolfgang and Kreienberg, Rolf and Stein, Roland and St{\"u}ber, Tanja and Schwentner, Lukas and Bartmann, Catharina and W{\"o}ckel, Achim},
  title     = {Do Patients with Luminal A Breast Cancer Profit from Adjuvant Systemic Therapy? A Retrospective Multicenter Study},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0168730},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178217},
  year      = {2016},
  abstract  = {Background Luminal A breast cancers respond well to anti-hormonal therapy (HT), are associated with a generally favorable prognosis and constitute the majority of breast cancer subtypes. HT is the mainstay of treatment of these patients, accompanied by an acceptable profile of side effects, whereas the added benefit of chemotherapy (CHT), including anthracycline and taxane-based programs, is less clear-cut and has undergone a process of critical revision. Methods In the framework of the BRENDA collective, we analyzed the benefits of CHT compared to HT in 4570 luminal A patients (pts) with primary diagnosis between 2001 and 2008. The results were adjusted by nodal status, age, tumor size and grading. Results There has been a progressive reduction in the use of CHT in luminal A patients during the last decade. Neither univariate nor multivariate analyses showed any statistically significant differences in relapse free survival (RFS) with the addition of CHT to adjuvant HT, independent of the nodal status, age, tumor size or grading. Even for patients with more than 3 affected lymph nodes, there was no significant difference (univariate: p = 0.865; HR 0.94; 95\% CI: 0.46-1.93; multivariate: p = 0.812; HR 0.92; 95\% CI: 0.45-1.88). Conclusions The addition of CHT to HT provides minimal or no clinical benefit at all to patients with luminal A breast cancer, independent of the RFS-risk. Consequently, risk estimation cannot be the initial step in the decisional process. These findings-that are in line with several publications-should encourage the critical evaluation of applying adjuvant CHT to patients with luminal A breast cancer.},
  language  = {en}
}
@article{DiessnerWischnewskyStueberetal.2016,
  author    = {Diessner, Joachim and Wischnewsky, Manfred and St{\"u}ber, Tanja and Stein, Roland and Krockenberger, Mathias and H{\"a}usler, Sebastian and Janni, Wolfgang and Kreienberg, Rolf and Blettner, Maria and Schwentner, Lukas and W{\"o}ckel, Achim and Bartmann, Catharina},
  title     = {Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer},
  series = {BMC Cancer},
  volume    = {16},
  journal   = {BMC Cancer},
  number    = {307},
  doi       = {10.1186/s12885-016-2345-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161173},
  year      = {2016},
  abstract  = {Background The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. Methods This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms "exhausted CHAID (Chi-square Automatic Interaction Detectors)" and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Results Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 \% of patients with luminal A or luminal B (ABC-patients) and 11.4 \% with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p < 0.001). Five different mathematical models confirmed this correlation. The second important risk factor is the age at primary diagnosis. Moreover, BC subcategories influence the overall survival from date of metastatic disease of patients with bone-only metastases. Patients with bone-only metastases and TNBC (p < 0.001; HR = 7.47 (95 \% CI: 3.52-15.87) or HER2 overexpressing BC (p = 0.007; HR = 3.04 (95 \% CI: 1.36-6.80) have the worst outcome compared to patients with luminal A or luminal B tumours and bone-only metastases. Conclusion The bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.},
  language  = {en}
}
@article{MartratMaxwellTominagaetal.2011,
  author    = {Martrat, Griselda and Maxwell, Christopher A. and Tominaga, Emiko and Porta-de-la-Riva, Montserrat and Bonifaci, N{\´u}ria and G{\´o}mez-Bald{\´o}, Laia and Bogliolo, Massimo and L{\´a}zaro, Conxi and Blanco, Ignacio and Brunet, Joan and Neveling, Kornelia and et al,},
  title     = {Exploring the link between MORF4L1 and risk of breast cancer},
  series = {Breast Cancer Research},
  volume    = {13},
  journal   = {Breast Cancer Research},
  number    = {R40},
  doi       = {10.1186/bcr2862},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169119},
  pages     = {1-14},
  year      = {2011},
  abstract  = {Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.},
  language  = {en}
}