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1.
Ther Adv Med Oncol ; 13: 17588359211042301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691243

RESUMO

Background: Bendamustine, a medication approved for the treatment of indolent non-Hodgkin lymphoma, has already shown anticancer activity in metastatic breast cancer (MBC). Here, we present the results of a phase II trial of bendamustine in combination with capecitabine in pre-treated patients with MBC. Patients and methods: AGMT MBC-6 is a multicentre, open-label, single-arm phase II study in HER2-negative MBC. All patients were pre-treated with anthracyclines and/or taxans and had measurable disease. Patients received per os 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine intravenously on days 1 and 8 of a 3-week cycle for a maximum of eight cycles, followed by a capecitabine maintenance therapy. The primary endpoint was overall response rate (ORR). Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centres. The median age was 60 years (range 29-77). Twenty-five per cent of patients had triple-negative breast cancer (TNBC) and 93% showed visceral involvement. With 17 partial and one complete remission, ORR was 46%. Median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI) 6.1-10.7]. The most common non-haematological adverse events (AEs) of grade 3 were hand-foot syndrome (13%), fatigue (10%), nausea (8%), and dyspnoea (8%). One grade 4 non-haematological AE (hepatic failure) and three grade 4 haematological AEs (neutropenia) were observed. One patient died of restrictive cardiomyopathy, in which a relationship to capecitabine cannot be excluded, but seems unlikely. Conclusion: The combination of capecitabine and bendamustine shows promising efficacy and moderate toxicity. Further evaluation of this drug combination is warranted.The clinical trial AGMT MBC-6 was registered at ClinicalTrials.gov, (https://clinicaltrials.gov/; identifier: NCT01891227).

2.
Br J Cancer ; 124(11): 1795-1802, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33762716

RESUMO

BACKGROUND: Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences. METHODS: HER2-negative early-stage breast cancer patients were recruited to this randomised multicentre Phase 2 study. Patients in the chemotherapy cohort (n = 311) were additionally randomised to a conventional or reversed sequence of epirubicin/cyclophosphamide and docetaxel. Residual cancer burden (RCB) with/without tecemotide was defined as primary study endpoint; RCB in the two chemotherapy groups was a key secondary endpoint. RESULTS: No significant differences in terms of RCB 0/I (40.1% vs. 37.2%; P = 0.61) or pathologic complete response (pCR) rates (24.3% vs. 25%, P = 0.89) were observed between conventional or reverse chemotherapy sequence. No new safety signals were reported, and upfront docetaxel did not result in decreased rates of treatment delay or discontinuation. CONCLUSION: Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option.

3.
Eur J Cancer ; 132: 43-52, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32325419

RESUMO

BACKGROUND: Immune-based strategies represent a promising approach in breast cancer (BC) treatment. The glycoprotein mucin-1 (MUC-1) is overexpressed in more than 90% of BC patients, and is targeted by the cancer vaccine tecemotide. We have investigated the efficacy and safety of tecemotide when added to neoadjuvant standard-of-care (SoC) treatment in early BC patients. PATIENTS AND METHODS: A total of 400 patients with HER2-early BC were recruited into this prospective, multicentre, randomised 2-arm academic phase II trial. Patients received preoperative SoC treatment (chemotherapy or endocrine therapy) with or without tecemotide. Postmenopausal women with oestrogen receptor (ER)+++, or ER++ and Ki67 < 14%, and G1,2 tumours ('luminal A' tumours) received 6 months of letrozole. Postmenopausal patients with triple-negative, ER-/+/++ and Ki67 ≥ 14%, and with G3 tumours, as well as premenopausal patients, received four cycles of epirubicin/cyclophosphamide plus four cycles of docetaxel. Primary end-point was residual cancer burden (RCB; 0/I versus II/III) at surgery. Secondary end-points included pathological complete response (pCR), safety, and quality of life. FINDINGS: We observed no significant difference in RCB 0/I rates between patients with (36.4%) and without (31.9%) tecemotide in the overall study population (p = 0.40) nor in endocrine and chemotherapy-treated subgroups (25.0% versus 13.3%, p = 0.17; 39.6% versus 37.8%, p = 0.75, respectively). The addition of tecemotide did not affect overall pCR rates (22.5% versus 17.4%, p = 0.23), MUC-1 expression, or tumour-infiltrating lymphocytes content. Tecemotide did not increase toxicity when compared to SoC therapy alone. INTERPRETATION: Neoadjuvant tecemotide is safe, but does not improve RCB or pCR rates in patients receiving standard neoadjuvant therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Vacinas Anticâncer/uso terapêutico , Glicoproteínas de Membrana/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Segurança do Paciente , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
4.
Breast ; 50: 64-70, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062536

RESUMO

BACKGROUND: STEPAUT, an Austrian non-interventional study, evaluated the safety and efficacy of everolimus plus exemestane in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) recurring/progressing on/after nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice. METHODS: Postmenopausal women with HR+, HER2- ABC progressing on/after NSAIs receiving everolimus plus exemestane in accordance with routine practice and the current version of Summary of Product Characteristics were eligible. Planned individual observation period corresponded to the duration of treatment until formal study end. RESULTS: Overall, 236 patients (median age: 65 years) were enrolled at 17 sites across Austria. The median progression-free survival (mPFS) in the overall population was 9.5 months (95% confidence interval [CI]: 8.6-10.7 months). The mPFS (95% CI) in patients who received everolimus 10 and 5 mg was 9.9 months (7.3-11.5 months) and 8 months (4.7-10.7 months), respectively. The median time to progression was numerically longer in patients who had a therapy break (11.9 months, 95% CI: 10.0-14.6 months) versus those who did not have any therapy break (10.7 months, 95% CI: 8.9-12.6 months). Patients experienced grade 1 (53.7%), grade 2 (35.9%), grade 3 (9.9%), grade 4 (0.2%) adverse events (AEs). The most common AEs of any grade were stomatitis, mucositis (53.8%), rash, exanthema (29.7%), loss of appetite, nausea (28.4%). CONCLUSIONS: Real-world safety and efficacy data from STEPAUT were consistent with results from BOLERO-2, supporting everolimus plus exemestane as a suitable treatment option for HR+, HER2- ABC recurring/progressing on/after NSAIs.


Assuntos
Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Everolimo/uso terapêutico , Padrões de Prática Médica , Idoso , Áustria/epidemiologia , Feminino , Humanos , Pós-Menopausa , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
5.
Ann Surg ; 269(6): 1163-1169, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31082916

RESUMO

BACKGROUND: Conflicting evidence exists regarding the value of surgical resection of the primary in stage IV breast cancer patients. OBJECTIVE: The prospective randomized phase III ABCSG-28 POSYTIVE trial evaluated median survival comparing primary surgery followed by systemic therapy to primary systemic therapy in de novo stage IV breast cancer. METHODS: Between 2011 and 2015, 90 previously untreated stage IV breast cancer patients were randomly assigned to surgical resection of the primary tumor followed by systemic therapy (Arm A) or primary systemic therapy (Arm B) in Austria. Overall survival (OS) was defined as the primary study endpoint. RESULTS: The trial was stopped early due to poor recruitment. Ninety patients (45 arm A, 45 arm B) were included; median follow-up was 37.5 months. Patients in the surgery arm had more cT3 breast cancer (22.2% vs 6.7%) and more cN2 staging (15.6% vs 4.4%). Both groups were well balanced with respect to the type of first-line systemic treatment. Median survival in arm A was 34.6 months, versus 54.8 months in the nonsurgery arm [hazard ratio (HR) 0.691, 95% confidence interval (95% CI) 0.358-1.333; P = 0.267]; time to distant progression was 13.9 months in the surgery arm and 29.0 months in the nonsurgery arm (HR 0.598, 95% CI 0.343-1.043; P = 0.0668). CONCLUSION: The prospective phase III trial ABCSG-28 (POSYTIVE) could not demonstrate an OS benefit for surgical resection of the primary in breast cancer patients presenting with de novo stage IV disease.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Mastectomia , Idoso , Idoso de 80 Anos ou mais , Áustria , Neoplasias da Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
6.
Clin Breast Cancer ; 18(1): 38-44, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29017754

RESUMO

PURPOSE: Health behavior (HB) has been identified as contributing to breast cancer (BC) disease outcome. The present study was subjected to gain more in-depth insight into breast cancer survivors' (BCS) HB and its associations with patient quality of life (QOL) outcome. We investigated HB focusing on eating disturbances comparing the latter with a reference population sample (PS). MATERIALS AND METHODS: The research cohort included 303 BCS completing a comprehensive patient-reported-outcome assessment on HB (eating disturbances, exercise, substance use) and QOL. Data from an age- and education-matched reference PS (n = 303) on eating disturbances were included. RESULTS: Overall, 30% of BCS were overweight; 11.7% of BCS (2-11 years after diagnosis, mean = 5.2 years) reported eating disturbances compared with 5% of PS (P < .05). Approximately three-fourths of BCS indicated they exercise regularly, one-fourth smoke regularly, and 30% consume alcohol. Lower consumption of analgesics and tranquilizers, higher frequency of exercise, lower eating concern (EDE-Q), younger age, and lower body mass index were significant predictors for better physical QOL. Lower eating and shape concern were next to age-identified predictive for better psychological QOL. DISCUSSION: Obesity and eating disturbances are a considerable HB problem in women with a history of BC. Considering that HB is predictive for long-term QOL in BCS, routine counseling on HB should be integrated into survivorship care to increase patient education and contribute to behavioral changes.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Comportamentos Relacionados com a Saúde/fisiologia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Áustria/epidemiologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/fisiopatologia , Sobreviventes de Câncer/estatística & dados numéricos , Estudos de Casos e Controles , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/psicologia , Fumar/epidemiologia , Fumar/psicologia , Adulto Jovem
7.
BMC Cancer ; 17(1): 685, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29037213

RESUMO

BACKGROUND: Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. METHODS: A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. RESULTS: Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. CONCLUSIONS: Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Análise Custo-Benefício , Recidiva Local de Neoplasia/tratamento farmacológico , Áustria , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Terapia Combinada/economia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Medicina de Precisão , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
8.
BMC Cancer ; 17(1): 599, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854893

RESUMO

BACKGROUND: Cancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients' follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC). METHODS: BCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting. Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire. RESULTS: One hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS. CONCLUSION: SH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.


Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Adulto , Ansiedade/fisiopatologia , Ansiedade/psicologia , Imagem Corporal/psicologia , Estudos Transversais , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Autorrelato , Comportamento Sexual/fisiologia , Comportamento Sexual/psicologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia , Saúde Sexual , Inquéritos e Questionários
9.
Breast Care (Basel) ; 12(1): 8-14, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28611535

RESUMO

Triple-negative breast cancers (TNBCs) are defined as tumors that are negative for estrogen, progesterone and HER-2 receptor. At a percentage of 10-20% TNBCs represent a minority in all breast cancers. However, because of the poor prognosis this particular subtype, triple negative disease accounts for a disproportionate number of metastatic cases and breast cancer deaths. Identification of its subtypes is essential for understanding the biological characteristics and clinical behavior of TNBC, as well as for developing personalized treatments. This review will focus on the great progress that has been made in the past few years on identifying new targets in TNBC subtypes and a variety of new treatment options that are on the verge of routine clinical application.

10.
EBioMedicine ; 21: 79-85, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28629908

RESUMO

BACKGROUND: Previous studies on breast cancer (BC), underarm cosmetic products (UCP) and aluminum salts have shown conflicting results. We conducted a 1:1 age-matched case-control study to investigate the risk for BC in relation to self-reported UCP application. METHODS: Self-reported history of UCP use was compared between 209 female BC patients (cases) and 209 healthy controls. Aluminum concentration in breast tissue was measured in 100 cases and 52 controls. Multivariable conditional logistic regression analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for established BC risk factors. FINDINGS: Use of UCP was significantly associated with risk of BC (p=0.036). The risk for BC increased by an OR of 3.88 (95% CI 1.03-14.66) in women who reported using UCP's several times daily starting at an age earlier than 30years. Aluminum in breast tissue was found in both cases and controls and was significantly associated to self-reported UCP use (p=0.009). Median (interquartile) aluminum concentrations were significantly higher (p=0.001) in cases than in controls (5.8, 2.3-12.9 versus 3.8, 2.5-5.8nmol/g). INTERPRETATION: Frequent use of UCPs may lead to an accumulation of aluminum in breast tissue. More than daily use of UCPs at younger ages may increase the risk of BC.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Cosméticos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alumínio/química , Estudos de Casos e Controles , Cosméticos/química , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Risco , Adulto Jovem
11.
J Psychosom Res ; 89: 39-45, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27663109

RESUMO

OBJECTIVE: We investigated the psychosocial consequences of genetic counseling and testing (GCT) for hereditary breast and ovarian cancer (HBOC) at follow-up in a "real-life" sample of counselees at an Austrian tertiary care center. METHODS: The study cohort included counselees who had undergone genetic counseling for HBOC and completed a follow-up self-report questionnaire battery on psychosocial outcomes (quality of life, psychological distress, satisfaction with counseling and decisions). For comparison of distress, we recruited a reference sample of breast cancer survivors (BCS; n=665) who had not requested GCT in the same setting. RESULTS: Overall, counselees did not exhibit increased levels of anxiety and depression when compared to BCS. No specific follow-up deleterious psychosocial consequences were detected among the former group. Of the 137 counselees, 22.6% and 9.8% experienced clinically relevant levels of anxiety and depression, respectively, at an average follow-up time of 1.8years. However, both anxiety and depression significantly decreased with time and were alike between counselees with and without cancer diagnosis. Follow-up cancer worry seems to be significantly higher among counselees who had not undergone genetic testing or were undecided about it than among counselees who had been tested. CONCLUSION: Our results strongly support GCT as part of routine care for patients with HBOC. The risk factors of increased distress in specific subgroups of counselees, such as recent cancer diagnosis or uncertainty about testing, warrant further exploration and specific attention in clinical routines. Particularly, the psychological needs of undecided counselees warrant ongoing attention and potential follow-ups.


Assuntos
Neoplasias da Mama/psicologia , Aconselhamento Genético/psicologia , Neoplasias Ovarianas/psicologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Adulto , Idoso , Ansiedade/psicologia , Ansiedade/terapia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Estudos Transversais , Depressão/psicologia , Depressão/terapia , Feminino , Seguimentos , Aconselhamento Genético/tendências , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Testes Genéticos/tendências , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Qualidade de Vida/psicologia , Fatores de Risco , Inquéritos e Questionários
12.
Eur J Hum Genet ; 24(2): 258-62, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26014432

RESUMO

Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Testes Genéticos , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA2/genética , Neoplasias da Mama/patologia , Códon de Terminação/genética , Feminino , Efeito Fundador , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/patologia
13.
Wien Med Wochenschr ; 165(19-20): 387-94, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26471371

RESUMO

We reviewed the status of the use of the prophylactic long-acting granulocyte colony-stimulating factors (G-CSFs) pegfilgrastim and lipegfilgrastim in gynecologic malignancies. Long-acting G-CSFs should not be used in weekly regimens. Filgrastim is not indicated in patients with febrile and/or severe neutropenia after administration of long-acting G-CSF in the same cycle. One study has shown a moderate effect on febrile neutropenia of ciprofloxacin when co-administered with pegfilgrastim. There is broad evidence from meta-analyses that pegfilgrastim effectively reduces severe neutropenia. In parallel, its adverse effects have been studied extensively. All-cause mortality was significantly reduced by pegfilgrastim. The glycopegylated long-acting G-CSF, lipegfilgrastim has demonstrated antineutropenic efficacy similar to that of pegfilgrastimin in one breast cancer study. In another pivitol non-small cell lung cancer study, impaired survival was observed in the lipegfilgrastim group during the first 30 days of study. The European Medicines Agency claimed more profound safety data to be provided for lipegfilgrastim by 2017.


Assuntos
Neoplasias dos Genitais Femininos/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Causas de Morte , Ciprofloxacina/uso terapêutico , Contraindicações , Preparações de Ação Retardada , Progressão da Doença , Quimioterapia Combinada , Feminino , Filgrastim , Neoplasias dos Genitais Femininos/mortalidade , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/mortalidade , Polietilenoglicóis , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Análise de Sobrevida
14.
Lancet ; 386(9992): 433-43, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040499

RESUMO

BACKGROUND: Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. METHODS: In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. INTERPRETATION: Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. FUNDING: Amgen.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/complicações , Fraturas Ósseas , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Áustria , Densidade Óssea/fisiologia , Neoplasias da Mama/tratamento farmacológico , Denosumab , Método Duplo-Cego , Feminino , Fraturas Ósseas/complicações , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Suécia , Resultado do Tratamento
15.
Wien Klin Wochenschr ; 127(15-16): 652-4, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26109557

RESUMO

In Austria, 700 women are diagnosed every year with ovarian carcinoma. Approximately 15% of the patients with epithelial ovarian cancer have a germline mutation in the BRCA1 or BRCA2 genes. The increased incidence of breast and/or ovarian cancer in genetically related family members has given rise to the term "hereditary breast and ovarian cancer syndrome" (HBOC). Some 25-55% of these in-family diseases are attributed to germline mutations of BRCA1 or BRCA2, and approximately 5-10% to other known tumor predisposition syndromes. The remaining persons may carry mutations in as yet unidentified genes. HBOC caused by BRCA1 and BRCA2 mutations is an autosomal dominant disorder with high penetrance. BRCA1 and BRCA2 encode for so-called tumor suppressor proteins. Inherited functional mutations of these genes cause loss of function of the respective allele. Loss of function of the second allele causes complete loss of the corresponding protein and facilitates the development of a malignancy.The Association of Gynecologic Oncology recommends that testing for a germline mutation in BRCA1 or BRCA2 should be offered to all patients with epithelial ovarian cancer. When mutations in BRCA1, BRCA2, or other cancer-susceptibility genes have been identified, patients with ovarian carcinoma can be treated with new, innovative therapies. This recommendation is intended as a standard guideline for genetic testing of patients with an ovarian carcinoma.


Assuntos
Detecção Precoce de Câncer/normas , Testes Genéticos/normas , Oncologia/normas , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Guias de Prática Clínica como Assunto , Áustria , Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Feminino , Predisposição Genética para Doença/genética , Ginecologia/normas , Humanos , Polimorfismo de Nucleotídeo Único/genética
16.
Arch Gynecol Obstet ; 292(4): 739-47, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25814297

RESUMO

Dual-energy contrast-enhanced mammography is one of the latest developments in breast care. Imaging with contrast agents in breast cancer was already known from previous magnetic resonance imaging and computed tomography studies. However, high costs, limited availability-or high radiation dose-led to the development of contrast-enhanced spectral mammography (CESM). We reviewed the current literature, present our experience, discuss the advantages and drawbacks of CESM and look at the future of this innovative technique.


Assuntos
Neoplasias da Mama/diagnóstico , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Doses de Radiação , Intensificação de Imagem Radiográfica
17.
BMC Cancer ; 14: 958, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25510351

RESUMO

BACKGROUND: Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome. The molecular profile of triple-negative breast cancers (TNBCs) overlaps with that of basal-like breast cancers that in turn show similarities with high-grade serous ovarian and endometrial carcinoma. L1CAM is an established biomarker for the latter cancers and we showed before that approximately 18% of primary breast cancers are positive for L1CAM and have a bad prognosis. Here we analysed the expression of L1CAM breast cancer subtypes. METHODS: We analyzed mRNA and protein expression data from different breast cancer cohorts for L1CAM, estrogen receptor, progesterone receptor, Her-2 and Androgen receptor (AR) and correlated the data. We performed Western blot analysis on tumor cell lysates and carried out chromatin-immuno-precipitation (CHIP) after AR overexpression. RESULTS: We find that L1CAM is expressed preferentially though not exclusively in TNBCs. Using the human cancer genome atlas database and two independent breast cancer cohorts we find that L1CAM is inversely correlated with androgen receptor (AR) expression. We found that L1CAM(high)AR(low) primary breast tumors have the worst clinical outcome. Overexpression of AR in MDA-MB436 breast cancer cells decreased L1CAM expression at the protein and mRNA level and CHIP-analysis revealed binding of AR to the L1CAM promoter region. CONCLUSIONS: These results suggest that L1CAM in breast cancer is under AR control. The data also strongly advocate the use of L1CAM assessment in breast cancer diagnosis. We suggest that L1CAM expression could be causally related to the bad prognosis of TNBCs.


Assuntos
Regulação Neoplásica da Expressão Gênica , Molécula L1 de Adesão de Célula Nervosa/genética , Receptores Androgênicos/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sítios de Ligação , Biomarcadores Tumorais , Linhagem Celular Tumoral , Bases de Dados Genéticas , Feminino , Humanos , Pessoa de Meia-Idade , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade
19.
Eur J Cancer ; 50(12): 2134-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24910416

RESUMO

BACKGROUND: Deregulation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signalling has been associated with poor clinical outcome in breast cancer and other cancers. The recently discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Potential links between genetic variants of the MACC1 gene and survival in breast cancer patients are unknown. In the present study, we therefore aimed to investigate the influence of MACC1 polymorphisms on event-free and overall survival in patients with human epidermal growth factor 2 (HER2)-positive breast cancer. METHODS: The present study included 164 consecutive white patients with HER2-positive breast cancer. Three MACC1 polymorphisms, rs1990172, rs975263 and rs3735615, already associated with cancer prognosis or with potential functional effects, were genotyped by the 5' nuclease assay. RESULTS: Multivariate Cox regression analysis adjusted for age and tumour stage showed increased risk for progression or death for carriers of the rare allele (G-allele) of single nucleotide polymorphism (SNP) rs1990172 (hazard ratios (HR) = 2.26; p = 0.004 and HR = 3.13; p = 0.001 for event-free survival and overall survival, respectively). In addition, we were able to demonstrate an adverse effect on cancer prognosis for carriers of the rare allele (T-allele) of SNP rs975263 (HR = 2.17; p = 0.007 and HR = 2.80; p = 0.003 for event-free survival and overall survival, respectively). The rare allele (C-allele) of SNP rs3735615 showed a significant protective impact on event-free survival as well as overall survival (HR = 0.25; p = 0.001, and HR = 0.16; p = 0.001, respectively). CONCLUSIONS: This study provides first evidence that MACC1 polymorphisms are associated with clinical outcome for HER2-positive breast cancer patients. Further studies are warranted to validate these findings.


Assuntos
Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptor ErbB-2/metabolismo , Análise de Sobrevida , Transativadores
20.
Clin Chim Acta ; 434: 41-7, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24768783

RESUMO

BACKGROUND: Afamin is a liver-derived plasma glycoprotein with vitamin E-binding properties and a putative function in fertility. This study evaluated serum afamin concentrations during and postpartum to uncomplicated pregnancies and investigated a potential association between afamin concentrations and pregnancy outcome. METHODS: Afamin serum concentrations were measured in women with uncomplicated pregnancies in a retrospective cohort (n=466) at different gestational ages and a prospective observational study (n=76) in the first, second and third trimester. Furthermore, afamin was determined in the first trimester in a cross-sectional pilot study including women with preeclampsia (PE), pregnancy-induced hypertension (PIH) and women without pregnancy complications (n=13 each). Finally, expression of afamin was investigated in human placental tissue by RT-PCR and immunohistochemistry. RESULTS: Afamin concentrations increased linearly almost two-fold during pregnancy in both retrospective and prospective studies in women without pregnancy complications with median afamin serum concentrations of 61.9 mg/l, 79.6 mg/l, and 98.6 mg/l in the first, second, and third trimester, respectively. After delivery, median afamin concentrations decreased to baseline values of 54.6 mg/l. In the pilot study with pregnancy complications, women with PE displayed significantly higher median afamin concentrations than did women with uncomplicated pregnancy (70.0 mg/l vs. 55.4 mg/l, P=0.007). Expression analyses revealed no placental afamin expression at either mRNA or protein level in uncomplicated pregnancy. CONCLUSION: A linear increase in the maternally expressed glycoprotein afamin during pregnancy may serve as basic reference for subsequent investigations of afamin in pregnancy-related disorders.


Assuntos
Proteínas de Transporte/sangue , Regulação da Expressão Gênica/fisiologia , Glicoproteínas/sangue , Pré-Eclâmpsia/metabolismo , Vitamina E/metabolismo , Adulto , Estudos Transversais , Feminino , Humanos , Projetos Piloto , Pré-Eclâmpsia/sangue , Gravidez , Trimestres da Gravidez , Estudos Retrospectivos , Albumina Sérica , Albumina Sérica Humana , Adulto Jovem
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