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1.
Sci Adv ; 7(13)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33771873

RESUMO

Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5's relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system.

2.
Gynakologe ; : 1-7, 2021 Mar 18.
Artigo em Alemão | MEDLINE | ID: mdl-33758428

RESUMO

From March 3 to October 13, 2020, 27 cases with diabetes comorbidity have been recorded in the CRONOS registry (Covid-19 Related Obstetric and Neonatal Outcome Study in Germany) among 262 registered women with SARS-CoV­2 infection during their pregnancy. Of those, 21 presented with gestational diabetes, 5 with type 2 diabetes and 1 with type 1 diabetes. About half of the women were asymptomatic and were diagnosed via general screening at hospital admission. The most common symptoms were nasal congestion, cough, tiredness, malaise and changes in smell and taste. The majority of pregnant women showed a mild to moderate course, three women were admitted to the intensive care unit and none required invasive ventilation. In the type 2 diabetes group, there were two cases with late fetal death (37 and 40 weeks of gestation) and one with a malformation, an association with diabetes being most likely. Pregnant women with diabetes mellitus represent a special subgroup; 1 in 10 women in this small cohort required intensive care monitoring due to COVID-19. In addition, this case series underscores the need for unrestricted access to pregnancy care, especially in times of pandemic, for optimal perinatal outcome.

3.
Int J Cancer ; 148(2): 307-319, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32851660

RESUMO

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

4.
Sci Rep ; 10(1): 15750, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978482

RESUMO

The immunosuppressive human leukocyte antigens HLA-G and HLA-F are expressed on trophoblast and malignant cells. Four membrane-bound and three soluble HLA-G protein isoforms have been described, which have different immunosuppressive potentials. HLA-F has three transcript variants, resulting in three different protein isoforms. The aim of this study was to evaluate the prognostic and predictive value of HLA-G and HLA-F protein isoform expression patterns in patients with breast cancer. Core biopsies were taken at diagnosis in patients with HER2+ (n = 28), luminal B-like (n = 49) and triple-negative (n = 38) breast cancers who received neoadjuvant chemotherapy. Expression levels of HLA-F and -G were correlated with the pathological complete response (pCR). Protein expression was determined by Western blot analysis, using two antibodies for each HLA, specific for different isoforms. The protein expression of HLA isoforms did not significantly differ between breast cancer subtypes. However, some initial indications were found for an association between the soluble HLA-G6 protein isoform and pCR in HER2+ breast cancer. The study provides preliminary evidence for the evaluation of HLA-G isoform expression, in particular HLA-G6, as a possible new marker for pCR in HER2+ breast cancer.

5.
Opt Express ; 28(11): 17047-17055, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32549514

RESUMO

Graduated optical filters are commonly used for spatial image control as they are capable of darkening the overexposed parts of the image specifically. However, they lack flexibility because each filter has a fixed transmission distribution. We herein present a fully controllable graduated filter based on the electrochromic device. Its graduated transmission distribution can be spatially controlled by the application of multiple electric potentials. In this way, the control of the gradient's position and its width, transmission and angular orientation is possible. Simulation of both the spatial potential distribution and the resultant optical absorption distribution are conducted to optimize the electrode configuration and furthermore to derive a control dataset that facilitates the adjustment and thus the application of the graduated filter. Based on three objective and quantitative criteria, we identify the electrode configuration with the highest flexibility in all four controls, manufacture the device using a gravure printing process for the nanoparticle electrodes and show its successful application.

6.
Int J Cancer ; 147(9): 2458-2468, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32580243

RESUMO

The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single-nucleotide polymorphisms in a large case-control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA-DQA1 and rs2844511 at MICA and HCP5, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79-0.99, P = .036; rs2844511: OR 1.17, 95% CI 1.04-1.31, P = .008) and with high-grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70-0.87, P = 7.1 × 10-6 ; rs2844511: OR 1.13, 95% CI 1.01-1.26, P = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75-0.91, P = 6.9 × 10-5 ; rs2844511: OR 1.14, 95% CI 1.04-1.26, P = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low-grade dysplasia (OR 1.26, 95% CI 1.04-1.54, P = .019). In case-only analyses, rs2844511 tended to predict HPV status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of MICA, HCP5 and HLA-DQA1, suggesting extensive co-regulation. All three genes were upregulated in HPV16-positive samples. In stratified analyses, rs9272117 was associated with HLA-DQA1 levels, specifically in HPV-positive samples, while rs2844511 was associated with MICA and HCP5 levels. The risk allele of rs2844511 was required for correlations between MICA or HCP5 with HLA-DQA1. Altogether, our results support 6p21.32-33 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of HLA-DQA1, HCP5 and MICA, which may contribute to tumor immune evasion.

7.
Complement Med Res ; 27(6): 431-439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544918

RESUMO

INTRODUCTION: Oncological second opinions are becoming increasingly important given more complex treatment strategies, simultaneously more patients use complementary and alternative medicine (CAM), and many comprehensive cancer centers initiate integrative medicine programs. The present study focuses on analyzing the effects of a second opinion in relation to attitudes toward CAM. METHODS: In this prospective study patients (n = 97) with a diagnosis of breast cancer or gynecological malignancies who had requested a second opinion received a questionnaire before and after the second opinion concerning their attitudes toward CAM. RESULTS: The majority of patients had breast cancer (72.2%, n = 70). Only 6.2% (n = 6) stated that they had been informed about CAM by the doctors who treated them first, 21.6% (n = 21) had received information about it when seeking the second opinion. After the first opinion, 42.3% (n = 41) wanted to try CAM, the same proportion trusted orthodox medicine alone. After the second opinion, 24 patients (24.7%) wanted to try CAM, while 38.1% (n = 37) relied exclusively on orthodox medicine. There was a significant correlation between an increased patients' need for information and interest in CAM (p = 0.02). CONCLUSIONS: Today, aspects of CAM still are very often no part of oncological first and second opinions. This might hence lead to discouraging patients to try out CAM and therefore integrative medicine programs in comprehensive cancer centers might be problem-solving.

8.
Br J Cancer ; 123(5): 793-802, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32555365

RESUMO

BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

9.
Arch Gynecol Obstet ; 301(5): 1299-1306, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32274639

RESUMO

PURPOSE: Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients' motives, subjective extent of information and satisfaction with communications. METHODS: This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. RESULTS: A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P < 0.0001), and satisfaction with doctor-patient communications increased (from 61.9 to 91.8%, P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. CONCLUSIONS: Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor-patient communications play a key role.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias dos Genitais Femininos/epidemiologia , Encaminhamento e Consulta , Feminino , Humanos , Pessoa de Meia-Idade , Motivação , Satisfação do Paciente , Estudos Prospectivos , Universidades
10.
Lancet Oncol ; 21(5): 699-709, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32305099

RESUMO

BACKGROUND: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab. METHODS: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251. FINDINGS: Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin-gemcitabine-bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3-21·7) in the experimental group and 11·3 months (8·0-18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7-14·2) in the experimental group versus 11·6 months (11·0-12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68-0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (<1%; large intestine perforation) and two patients in the standard group (1%; one case each of osmotic demyelination syndrome and intracranial haemorrhage). INTERPRETATION: Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer. FUNDING: F Hoffmann-La Roche.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias das Tubas Uterinas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália/epidemiologia , Áustria/epidemiologia , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Neoplasias das Tubas Uterinas/patologia , Feminino , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Platina/administração & dosagem , Platina/efeitos adversos , Polietilenoglicóis/administração & dosagem
11.
J Cancer Res Clin Oncol ; 146(4): 961-969, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31901975

RESUMO

OBJECTIVE: The primary therapy for intermediate- and high-risk endometrial cancer includes pelvic and paraaortic lymph node evaluation. Laparoscopic surgery is an increasingly popular intervention due to decreased risk and better short-term morbidity; however, a recent study casts doubt on the benefit of this approach in terms of oncological safety. In this cancer registry study, we sought to evaluate the benefit of laparoscopy versus laparotomy and retrospectively compared overall survival, recurrence rates, and recurrence-free survival among patients with intermediate- and high-risk endometrial cancer who underwent either laparoscopic or open surgery. METHODS: This observational study included 419 patients who have been treated from 2011 to 2017. We employed Kaplan-Meier method, and univariable and multivariable Cox-regression to compare overall survival, recurrence rates, and recurrence-free survival in 110 patients, who underwent laparoscopic, with 309 patients, who underwent open surgery. To address the confounding bias in this retrospective study, we also performed a propensity score matching (PSM) analysis including 357 patients (laparoscopy: n = 107; open surgery: n = 250). RESULTS: We found a benefit for laparoscopic over open surgery in patients with intermediate- and high-risk endometrial cancer for overall survival in both univariable (p = 0.002; PSM: p = 0.016) and multivariable analyses (p = 0.019; PSM: p = 0.007). In contrast, there was no statistically significant difference between both patient groups regarding the cumulative recurrence rates. A univariable analysis identified a significant benefit for laparoscopy regarding recurrence-free survival (p = 0.003; PSM: p = 0.029) but a multivariable analysis failed to confirm this finding (p = 0.108; PSM: p = 0.118). CONCLUSIONS: Our study provides evidence that laparoscopic systematic lymphadenectomy does not present a lower oncological efficacy than open surgery in the treatment of patients with endometrial cancer.


Assuntos
Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
12.
Arch Gynecol Obstet ; 301(1): 289-294, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31858234

RESUMO

PURPOSE: Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). METHODS: Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. RESULTS: Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. CONCLUSIONS: Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Terapia de Reposição de Estrogênios/efeitos adversos , Idoso , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Recidiva Local de Neoplasia , Prognóstico , Fatores de Risco , Taxa de Sobrevida
13.
Sci Rep ; 9(1): 15822, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676826

RESUMO

Passive graduated filters with fixed absorption profile are currently used in image recording to avoid overexposure. However, a whole set of filters with prescribed gradients is required to cope with changing illumination conditions. Furthermore, they demand mechanical adjustment during operation. To overcome these deficiencies we present a microfabricated active electrochromic graduated filter which combines multiple functionalities: The overall absorbance, the position of medium transmission as well as the magnitude of its gradient can be tuned continuously by electrical means. Live image control is possible using low operation voltages in the range of ±2 V to reach a high change in optical density ΔOD of 1.01 (400 nm to 780 nm) with a coloration and bleaching time 1.3 s and 0.2 s, respectively. Owing to their low volume and power consumption they are suitable for widespread applications like in smartphones, surveillance cameras or microscopes.

14.
Nat Commun ; 10(1): 4874, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653835

RESUMO

Fast switching 'transparent-to-black' electrochromic devices are currently under investigation as potential candidates in modern applications like e-papers or with additional functionality as ultracompact iris or switchable neutral filter in camera systems. However, recent electrochromic devices show either a lack of contrast or slow response times. To overcome these deficiencies we focus on a careful material composition of the colouring hybrid electrodes in our device. We have established a nanoporous Sb-doped SnO[Formula: see text] electrode as supporting electrode for chemisorbed electrochromic tetraphenylbenzidine molecules due to its good conductivity in the redox potential range of the molecule. This hybrid electrode was combined with a modified nanoporous TiO[Formula: see text] / viologen electrode to realize a high performance, complementary electrochromic device. Fast switching time constants of 0.5 s and concurrently high change in optical density [Formula: see text]OD = 2.04 at 605 nm confirm our successful concept. The achieved colouration efficiency of 440 cm[Formula: see text] C[Formula: see text] exceeds every high contrast device presented so far.

15.
BMC Cancer ; 19(1): 611, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227025

RESUMO

BACKGROUND: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. METHODS: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. RESULTS: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. CONCLUSIONS: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. TRIAL REGISTRATION: Clinical Trials Number: CFEM345DDE19.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Letrozol/uso terapêutico , Cooperação do Paciente , Pós-Menopausa , Idoso , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Estudos Prospectivos , Resultado do Tratamento , Recusa do Paciente ao Tratamento
16.
Int J Cancer ; 145(8): 2114-2121, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30901076

RESUMO

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Letrozol/uso terapêutico , Dor Musculoesquelética/fisiopatologia , Pós-Menopausa/efeitos dos fármacos , Idoso , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Artralgia/induzido quimicamente , Artralgia/fisiopatologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Letrozol/efeitos adversos , Pessoa de Meia-Idade , Dor Musculoesquelética/induzido quimicamente , Medição da Dor/métodos , Pós-Menopausa/fisiologia , Fatores de Tempo
17.
Breast Cancer Res Treat ; 175(3): 617-625, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30868391

RESUMO

PURPOSE: Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer. METHODS: This retrospective study analyzed a single-center cohort of 3140 patients with HER2-, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (< 10%), intermediate (10-19%), and high (≥ 20%) Ki-67 expression levels, as assessed by immunohistochemistry, and for subgroups relative to age, body mass index, disease stage, tumor grade, and (neo-)adjuvant chemotherapy. It was also investigated whether Ki-67 had different effects on DFS in these subgroups. RESULTS: The 5-year DFS rates for patients with low, intermediate, and high levels of Ki-67 expression were 0.90, 0.89, and 0.77, respectively. Ki-67 was able to further differentiate patients with an intermediate prognosis into different prognostic groups relative to common clinical parameters. Patients with stage II breast cancer had 5-year DFS rates of 0.84, 0.88, and 0.79 for low, intermediate, and high levels of Ki-67 expression. Ki-67 had different prognostic effects in subgroups defined by age and tumor grade. CONCLUSIONS: Ki-67 may help identify patients in intermediate prognostic groups with an unfavorable prognosis who may benefit from further therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Antígeno Ki-67/metabolismo , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
18.
Breast Cancer Res Treat ; 174(2): 453-461, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30603996

RESUMO

PURPOSE: Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients. METHODS: The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test. RESULTS: In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively). CONCLUSIONS: This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.


Assuntos
Neoplasias da Mama/patologia , Terapia de Reposição Hormonal/métodos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Idade de Início , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Análise de Regressão , Fatores de Risco
19.
Breast Cancer Res Treat ; 173(2): 319-328, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30324275

RESUMO

PURPOSE: Neoadjuvant combination treatment with chemotherapy (CTX), trastuzumab (TZM), and pertuzumab (PTZ) has been shown to result in higher pathological complete response rates (pCR) in comparison with treatment with chemotherapy and trastuzumab (CTX/TZM). This analysis was aimed at real-world validation of these results from prospective randomized trials. METHODS: In a retrospective analysis conducted in the PRAEGNANT network, patients were eligible for inclusion if they had either received neoadjuvant therapy with CTX/TZM or chemotherapy, trastuzumab, and pertuzumab (CTX/TZM/PTZ) and subsequently underwent surgery for their primary breast cancer. The effect of the two neoadjuvant regimens on pCR in addition to commonly applicable predictors of pCR was analyzed in 300 patients from three study sites, using logistic regression analyses with treatment arm, age, clinical tumor stage, grading, and hormone receptor status as predictors. RESULTS: pCR with complete disappearance of all tumor cells was seen in 30.2% (n = 58) of patients treated with CTX/TZM and in 52.8% (n = 57) of those treated with CTX/TZM/PTZ. CTX/TZM/PTZ was positively associated with pCR (adjusted odds ratio 2.44; 95% CI 1.49-4.02). Mastectomy rates were not influenced by the therapy. CONCLUSIONS: The results of clinical trials were confirmed in this dataset of patients who were treated outside of clinical trials in everyday routine work. pCR rates can be improved by 20% with pertuzumab in routine clinical use.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Trastuzumab/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Estudos Retrospectivos
20.
BMC Cancer ; 18(1): 1051, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373556

RESUMO

BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer. METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed. RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy. CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.


Assuntos
Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/terapia
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