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1.
Geburtshilfe Frauenheilkd ; 82(9): 932-940, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36110892

RESUMO

Introduction To date, the optimal axillary staging procedure for initially node-positive breast carcinoma patients after neoadjuvant chemotherapy (NACT) has been unclear. The aim of the AXSANA study is to prospectively compare different surgical staging techniques with respect to the oncological outcome and quality of life for the patients. Little is known about current clinical practice in Germany. Material and Methods In this paper we analyzed data from patients enrolled in the AXSANA study at German study sites from June 2020 to March 2022. Results During the period under investigation, 1135 patients were recruited at 143 study sites. More than three suspicious lymph nodes were initially found in 22% of patients. The target lymph node (TLN) was marked in 64% of cases. This was done with clips/coils in 83% of patients, with magnetic seeds or carbon suspension in 8% each, and with a radar marker in 1% of patients. After NACT, targeted axillary dissection (TAD) or axillary lymphadenectomy (ALND) were each planned in 48% of patients, and sentinel lymph node biopsy alone (SLNB) in 2%. Clinically, the nodal status after NACT was found to be unremarkable in 65% of cases. Histological lymph node status was correctly assessed by palpation in 65% of patients and by sonography in 69% of patients. Conclusion At the German AXSANA study sites, TAD and ALND are currently used as the most common surgical staging procedures after NACT in initially node-positive breast cancer patients. The TLN is marked with various markers prior to NACT. Given the inadequate accuracy of clinical assessment of axillary lymph node status after NACT, it should be questioned whether axillary dissection after NACT should be performed based on clinical assessment of nodal status alone.

2.
Geburtshilfe Frauenheilkd ; 82(2): 226-234, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35169390

RESUMO

Purpose Detection of SARS-CoV-2-infected pregnant women admitted to maternity units during a pandemic is crucial. In addition to the fact that pregnancy is a risk factor for severe COVID-19 and that medical surveillance has to be adjusted in infected women and their offspring, knowledge about infection status can provide the opportunity to protect other patients and healthcare workers against virus transmission. The aim of this prospective observational study was to determine the prevalence of SARS-CoV-2 infection among pregnant women in the hospital setting. Material and Methods All eligible pregnant women admitted to the nine participating hospitals in Franconia, Germany, from 2 June 2020 to 24 January 2021 were included. COVID-19-related symptoms, secondary diseases and pregnancy abnormalities were documented. SARS-CoV-2 RNA was detected by RT-PCR from nasopharyngeal swabs. The prevalence of acute SARS-CoV-2 infection was estimated by correcting the positive rate using the Rogan-Gladen method. The risk of infection for healthcare workers during delivery was estimated using a risk calculator. Results Of 2414 recruited pregnant women, six were newly diagnosed RT-PCR positive for SARS-CoV-2, which yielded a prevalence of SARS-CoV-2 infection of 0.26% (95% CI, 0.10 - 0.57%). Combining active room ventilation and wearing FFP2 masks showed an estimated reduction of risk of infection for healthcare workers in the delivery room to < 1%. Conclusions The prevalence of newly diagnosed SARS-CoV-2 infection during pregnancy in this study is low. Nevertheless, a systematic screening in maternity units during pandemic situations is important to adjust hygienic and medical management. An adequate hygienic setting can minimise the calculated infection risk for medical healthcare workers during patients' labour.

3.
Br J Cancer ; 123(1): 33-37, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32367072

RESUMO

BACKGROUND: Due to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients. METHODS: In this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018. The primary endpoint was disease-free survival (DFS). RESULTS: Between May 2009 and June 2018, 448 men with breast cancer were identified, with a median age at diagnosis of 69 years (range 27-96 years). The median follow-up was 39 months (range 3-89 months). Most tumours were larger than 20 mm; invasive ductal carcinoma was of no special histological type and with an intermediate grade of differentiation. Almost half of the men were diagnosed with positive axillary lymph nodes (43.5%). Hormone receptor (HR) positivity was observed in 98.4% of the patients. Notably, DFS among men who did not receive tamoxifen was significantly reduced as compared with those who underwent tamoxifen therapy (P = 0.002). The recurrence rate and mortality in the group of patients without and with tamoxifen treatment were 18.2% and 11.2%, respectively. The most common localisation of metastases was the bone. After adjustment for prognostic factors, we found that tamoxifen was found to reduce the recurrence rate by 68% (hazard ratio HR = 0.32; 95% confidence interval, CI: 0.14-0.74). CONCLUSIONS: Tamoxifen treatment was associated with improved DFS for MBC patients. CLINICAL TRIAL REGISTRATION: DRKS00009536.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama Masculina/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama Masculina/patologia , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Tamoxifeno/efeitos adversos
4.
Artigo em Inglês | MEDLINE | ID: mdl-32042437

RESUMO

BACKGROUND: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. METHODS: The concept for patient-centered "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study. RESULTS: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals. CONCLUSION: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective.

5.
Eur J Med Res ; 24(1): 32, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521205

RESUMO

BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.


Assuntos
Neoplasias da Mama/economia , Análise Custo-Benefício , Mastectomia/economia , Comportamento de Redução do Risco , Salpingo-Ooforectomia/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Salpingo-Ooforectomia/métodos , Adulto Jovem
6.
Sci Rep ; 8(1): 11584, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-30072748

RESUMO

Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10-5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10-23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs , Terapia Neoadjuvante , RNA Neoplásico/sangue , Neoplasias de Mama Triplo Negativas , Biópsia por Agulha , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Metabolômica , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
7.
Breast Cancer Res Treat ; 171(1): 85-94, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29725888

RESUMO

PURPOSE: BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. METHODS: Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. RESULTS: Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. CONCLUSIONS: BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genes BRCA1 , Genes BRCA2 , Mutação , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Análise Mutacional de DNA , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
8.
Eur J Med Res ; 22(1): 50, 2017 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-29178942

RESUMO

BACKGROUND: Little information is available concerning antioxidant effects of plant teas (water boiled) which are used more commonly in traditional Chinese medicine than other extracts. Thus, we addressed this issue by evaluating the ability of teas from four different plants with therapeutic potential on gynecological diseases. METHODS: The aqueous extracts of Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then their effects on copper-induced low-density lipoprotein cholesterol (LDL-C) oxidation were evaluated by spectrophotometric method. Density gradient ultracentrifugation method was recruited to isolate LDL-C from healthy individuals. RESULTS: Our results showed that adding 10, 20, and 30 µl S. persicae could increase the lag phase duration of LDL-C oxidation compared with control reaction 12, 21, and 33%, respectively. The most effective delay (87%) was observed when 30 µl H. diffusa was added to the reaction. In cases of L. cardiaca and C. zedoaria, we found no significant influence on the lag phase duration (p > 0.05). Moreover, our findings about starting point of the decomposition phase were almost in parallel with the lag phase results, as 30 µl of S. persicae or H. diffusa teas could significantly increase the initiation time of decomposition (p < 0.05). CONCLUSIONS: In conclusion our results showed that both S. persicae and H. diffusa teas and not L. cardiaca and C. zedoaria could have medicinal therapeutic effects partly through direct oxidation prevention.


Assuntos
Oxirredução/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , LDL-Colesterol/metabolismo , Curcuma , Hedyotis , Humanos , Leonurus , Chás Medicinais
9.
Geburtshilfe Frauenheilkd ; 77(8): 879-886, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28845052

RESUMO

INTRODUCTION: The care of patients with breast cancer is extremely complex and requires interdisciplinary care in certified facilities. These specialized facilities provide numerous services without being correspondingly remunerated. The question whether breast cancer surgery should be performed in an outpatient setting to reduce costs is increasingly being debated. This study compares inpatient surgical treatment with a model of the same surgery performed on an outpatient basis to examine the potential financial impact. MATERIAL AND METHODS: A theoretical model was developed and the DRG fees for surgical interventions to treat primary breast cancer were calculated. A theoretical 1-day DRG was then calculated to permit comparisons with outpatient procedures. The costs of outpatient surgery were calculated based on the remuneration rates of the AOP (Outpatient Surgery) Contract and the EBM (Uniform Assessment Scale) and compared to the costs of the 1-day DRG. RESULTS: The DRG fee for both breast-conserving surgery and mastectomy is higher than the fee paid in the context of the EBM system, although the same procedures were carried out in both systems. If a hospital were to carry out breast-conserving surgery as an outpatient procedure, the fee would be € 1313.81; depending on the type of surgery, the hospital would therefore only receive between 39.20% and 52.82% of the DRG fee. This was the case even for a 1-day treatment. Compared to the real DRG fees the difference would be even more striking. CONCLUSION: Carrying out breast cancer surgery as an outpatient procedure would result in a significant shortfall of revenues. Additional services from certified centers, such as the interdisciplinary planning of treatment, psycho-oncological and social-medical care with the involvement of relatives, detailed documentation, etc., which are currently provided without surcharge or adequate remuneration, could no longer be maintained. The quality of processes and excellent results which have been achieved and ultimately the care given by certified facilities would be significantly at risk.

10.
Heart Vessels ; 32(11): 1304-1313, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28567553

RESUMO

Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) are regulators of bone remodeling, but are also considered to play important roles in coronary artery disease (CAD). This study evaluated potential associations of soluble (s) RANKL and OPG with atherosclerosis-relevant cytokines. Blood was collected from 414 individuals who presented to our hospital with intermediate likelihood for CAD for further examination. Plasma concentrations of total sRANKL, OPG, and 20 cytokines were measured using sandwich-type enzyme-linked immunoassays (ELISAs; OPG and sRANKL) and Luminex laser-based fluorescence analysis and correlated with each other. The plasma levels of interferon-γ (IFN-γ) and the T-helper cell 2 cytokines interleukin-4 (IL-4) and IL-13 showed a positive correlation with sRANKL. The association with sRANKL levels was negative for IFN-γ-induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1). The strongest independent association with sRANKL in multivariable analyses was found for IFN-γ (positive) and IP-10 (negative), while IL-13 showed a positive and independent association with OPG plasma levels. OPG and sRANKL plasma levels correlate strongly and independently with specific circulating atherosclerosis-related cytokines in patients with intermediate cardiovascular risk.


Assuntos
Aterosclerose/sangue , Doença da Artéria Coronariana/sangue , Citocinas/sangue , Osteoprotegerina/sangue , Ligante RANK/sangue , Medição de Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/epidemiologia , Biomarcadores/sangue , Doença da Artéria Coronariana/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Fatores de Risco , Adulto Jovem
11.
Breast ; 32: 186-191, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28214786

RESUMO

OBJECTIVES: Risk-reducing surgeries are a feasible option for mitigating the risk in individuals with inherited susceptibility to cancer, but are the procedures cost-effective in the current health-care system in Germany? This study compared the health-care costs for bilateral risk-reducing mastectomy (BRRM) and risk-reducing (bilateral) salpingo-oophorectomy (RRSO) with cancer treatment costs that could potentially be prevented. PATIENTS AND METHODS: The analysis is based on interdisciplinary consultations with individuals with a high familial risk for breast and ovarian cancer at the University Breast Center for Franconia (Germany) between 2009 and 2013 (370 consultations; 44 patients with BRCA1 mutations and 26 with BRCA2 mutations). Health-care costs for risk-reducing surgeries in BRCA mutation carriers were calculated as reimbursements in the German diagnosis-related groups (DRG) hospital pricing system. These costs for the health-care system were compared with the potential cancer treatment costs that could possibly be prevented by risk-reducing surgeries. RESULTS: Long-term health-care costs can be reduced by risk-reducing surgeries after genetic testing in BRCA mutation carriers. The health-care system in Germany would have saved € 136,295 if BRRM had been performed and € 791,653 if RRSO had been performed before the development of cancer in only 50% of the 70 mutation carriers seen in our center. Moreover, in patients with combined RRSO and BRRM (without breast reconstruction), one further life-year for a 40-year-old BRCA mutation carrier would cost € 2,183. CONCLUSION: Intensive care, including risk-reducing surgeries in BRCA mutation carriers, is cost-effective from the point of view of the health-care system in Germany.


Assuntos
Grupos Diagnósticos Relacionados/economia , Custos de Cuidados de Saúde , Síndrome Hereditária de Câncer de Mama e Ovário/prevenção & controle , Ovariectomia/economia , Mastectomia Profilática/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/economia , Neoplasias da Mama/prevenção & controle , Análise Custo-Benefício , Feminino , Predisposição Genética para Doença , Alemanha , Síndrome Hereditária de Câncer de Mama e Ovário/economia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/economia , Neoplasias Ovarianas/prevenção & controle , Ovariectomia/métodos , Procedimentos Cirúrgicos Profiláticos/economia , Estudos Retrospectivos , Comportamento de Redução do Risco , Ubiquitina-Proteína Ligases/genética , Adulto Jovem
12.
J Surg Oncol ; 114(5): 613-618, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27378217

RESUMO

BACKGROUND AND OBJECTIVES: Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. METHODS: A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. RESULTS: Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P < 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days. CONCLUSIONS: Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. © 2016 Wiley Periodicals, Inc.


Assuntos
Carcinoma/cirurgia , Ascite Quilosa/etiologia , Neoplasias dos Genitais Femininos/cirurgia , Laparoscopia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Breast Cancer Res ; 18(1): 32, 2016 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-26968831

RESUMO

BACKGROUND: There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. METHODS: A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. RESULTS: Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. CONCLUSION: Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.


Assuntos
Adipócitos/patologia , Neoplasias da Mama/patologia , Mama/citologia , Células-Tronco Mesenquimais/patologia , Cultura Primária de Células/métodos , Adipócitos/metabolismo , Mama/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Plasticidade Celular/genética , Proliferação de Células/genética , Meios de Cultivo Condicionados , Células Epiteliais/patologia , Feminino , Humanos , Glândulas Mamárias Humanas/patologia , Células-Tronco Mesenquimais/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética
14.
Anticancer Res ; 36(1): 419-25, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26722076

RESUMO

BACKGROUND/AIM: The aim of this single-arm, prospective, multicenter phase II trial (MiX) was to increase treatment options for women with metastatic breast cancer pretreated with anthracycline and taxane by evaluation of the efficacy and toxicity of the combination of mitomycin C and capecitabine. PATIENTS AND METHODS: From 03/2004 to 06/2007, a total of 39 patients were recruited and received mitomycin C in combination with capecitabine. The primary end-point was to determinate the tumor response according to Response Evaluation Criteria in Solid Tumors and the rate of toxicities (safety). The secondary study objective was the evaluation of the time to progression (i.e. efficacy). RESULTS: The median time to progression was 9.3 months (95% confidence interval=6.6-12.0 months) and the median survival was 12.8 months (95% confidence interval=6.8-18.8 months). Most treatment-related adverse events were mild to moderate. CONCLUSION: Mitomycin C and capecitabine is a good taxane-free option in patients with metastatic breast cancer previously treated with anthracycline.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Mitomicina/uso terapêutico , Antraciclinas/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica
15.
Breast Care (Basel) ; 11(6): 398-404, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28228706

RESUMO

Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.

16.
Arch Gynecol Obstet ; 294(2): 343-51, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26711836

RESUMO

PURPOSE: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. METHODS: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. RESULTS: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival. CONCLUSIONS: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.


Assuntos
Tumores do Estroma Endometrial/patologia , Leiomiossarcoma/patologia , Tumor Mulleriano Misto/patologia , Sarcoma do Estroma Endometrial/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Tumores do Estroma Endometrial/mortalidade , Tumores do Estroma Endometrial/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Leiomiossarcoma/mortalidade , Leiomiossarcoma/terapia , Pessoa de Meia-Idade , Tumor Mulleriano Misto/mortalidade , Tumor Mulleriano Misto/terapia , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Sarcoma/patologia , Sarcoma do Estroma Endometrial/mortalidade , Sarcoma do Estroma Endometrial/terapia , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/cirurgia
17.
BMC Cancer ; 15: 751, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26487094

RESUMO

BACKGROUND: No screening programs are available for ovarian or endometrial cancer. One reason for this is the low incidence of the conditions, resulting in low positive predictive values for tests, which are not very specific. One way of addressing this problem might be to use risk factors to define subpopulations with a higher incidence. The aim of this study was to investigate the extent to which a medical history of endometriosis can serve as a risk factor for ovarian or endometrial cancer. METHODS: In a hospital-based case-control analysis, the cases represented patients with endometrial or ovarian cancer who were participating in studies aimed at assessing the risk for these diseases. The controls were women between the age of 40 and 85 who were invited to take part via a newspaper advertisement. A total of 289 cases and 1016 controls were included. Using logistic regression models, it was tested whether self-reported endometriosis is a predictor of case-control status in addition to age, body mass index (BMI), number of pregnancies and previous oral contraceptive (OC) use. RESULTS: Endometriosis was reported in 2.1 % of the controls (n = 21) and 4.8 % of the cases (n = 14). Endometriosis was a relevant predictor for case-control status in addition to other predictive factors (OR 2.63; 95 % CI, 1.28 to 5.41). CONCLUSION: This case-control study found that self-reported endometriosis may be a risk factor for endometrial or ovarian cancer in women between 40 and 85 years. There have been very few studies addressing this issue, and incorporating it into a clinical prediction model would require a more precise characterization of the risk factor of endometriosis.


Assuntos
Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Endometriose/complicações , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Fatores de Risco
18.
BMC Cancer ; 15: 587, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26272451

RESUMO

BACKGROUND: Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients' point of view. METHODS: The study included 2546 patients (breast cancer 21.6%, gynecological cancer 8.3%, obstetrics 32.7%, endometriosis 7.8%, fertility treatment 3.2%, other benign gynecological illnesses 19.2%, no information for 7.2%) in the outpatient clinic (45.2%) and in the in-patient sector (54.8%) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital's quality management system. RESULTS: As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6%), but only a few were also willing to take part in them (58.4%). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians. CONCLUSIONS: The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , Estudos Clínicos como Assunto/psicologia , Doenças dos Genitais Femininos/epidemiologia , Doenças dos Genitais Femininos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pesquisa Biomédica , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
19.
PLoS One ; 10(4): e0122106, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25875093

RESUMO

Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Proteínas de Transporte/metabolismo , Diagnóstico Precoce , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteínas de Transporte/sangue , Proteínas de Transporte/genética , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Mucoproteínas , Análise Multivariada , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Proteínas Oncogênicas , Prognóstico , Modelos de Riscos Proporcionais , Proteínas/metabolismo , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
BMC Med ; 12: 224, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25465851

RESUMO

BACKGROUND: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. METHODS: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. RESULTS: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 (95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. CONCLUSIONS: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , MicroRNAs/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/patologia , Fenótipo , Prognóstico
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