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1.
Lancet Oncol ; 21(10): 1283-1295, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002436

RESUMO

BACKGROUND: HER2-positive metastatic breast cancer is incurable and new treatments are needed. Addition of atezolizumab to trastuzumab emtansine might potentiate anticancer immunity and enhance the HER2-targeted cytotoxic activity of trastuzumab emtansine. We aimed to test this combination in HER2-positive advanced breast cancer that had progressed after previous treatment with trastuzumab and a taxane. METHODS: The KATE2 study is a randomised, double-blind, placebo-controlled, phase 2 study at 68 centres from nine countries across Asia, Australia, North America, and western Europe. Eligible patients were adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and centrally confirmed, measurable, HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. Patients were randomly assigned (2:1) either trastuzumab emtansine (3·6 mg/kg of bodyweight) plus atezolizumab (1200 mg) or trastuzumab emtansine plus placebo; all study drugs were administered by intravenous infusion every 3 weeks. Randomisation was done via an interactive voice and web response system using a permuted block scheme (block size of six) and was stratified by PD-L1 status, world region, and liver metastases. Patients, investigators, and study team members were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02924883, and the study has been completed. FINDINGS: Between Sept 26, 2016, and Aug 7, 2017, 330 patients were screened for the study, of whom 202 were randomly allocated either atezolizumab (n=133) or placebo (n=69). At the recommendation of the independent data monitoring committee, treatment assignment was unmasked on Dec 11, 2017, due to futility and the numerically higher frequency of adverse events among patients assigned atezolizumab. This date was set as the clinical cutoff for the primary analysis. Median follow-up was 8·5 months (IQR 6·1-11·5) for patients assigned atezolizumab and 8·4 months (5·3-11·1) for those assigned placebo. Median progression-free survival was 8·2 months (95% CI 5·8-10·7) for patients assigned atezolizumab versus 6·8 months (4·0-11·1) for those assigned placebo (stratified hazard ratio 0·82, 95% CI 0·55-1·23; p=0·33). The most common grade 3 or worse adverse events were thrombocytopenia (17 [13%] among 132 patients who received atezolizumab vs three [4%] among 68 who received placebo), increased aspartate aminotransferase (11 [8%] vs two [3%]), anaemia (seven [5%] vs 0), neutropenia (six [5%] vs three [4%]), and increased alanine aminotransferase (six [5%] vs two [3%]). Serious adverse events occurred in 43 (33%) of 132 patients who received atezolizumab and 13 (19%) of 68 patients who received placebo. One patient who received atezolizumab died due to a treatment-related adverse event (haemophagocytic syndrome). INTERPRETATION: Addition of atezolizumab to trastuzumab emtansine did not show a clinically meaningful improvement in progression-free survival and was associated with more adverse events. Further study of trastuzumab emtansine plus atezolizumab is warranted in a subpopulation of patients with PD-L1-positive, HER2-positive advanced breast cancer. FUNDING: F Hoffman-La Roche.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/patologia , Método Duplo-Cego , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Análise de Sobrevida , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(35): e21932, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871934

RESUMO

BACKGROUND: Xiaoaiping injection, extracted from the Chinese herb Marsdenia tenacissima (Roxb.) Wight et Arn., is a broad-spectrum anti-tumor drug and has been widely used for the treatment of breast cancer in China. The aim of this study is to systematically investigate the efficacy and safety of Xiaoaiping injection for the treatment of breast cancer. METHODS: We will perform the comprehensive literature search in the following databases from their inceptions to August 2020 for data extraction: PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of this study will provide evidence to show whether Xiaoaiping injection is an effective intervention for patient with breast cancer. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/4ZUXC.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Feminino , Humanos , Injeções , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Medicine (Baltimore) ; 99(33): e21498, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871996

RESUMO

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Lipídeos/sangue , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
6.
Anticancer Res ; 40(10): 5351-5354, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988853

RESUMO

BACKGROUND/AIM: The treatment of breast cancer has progressed considerably over the years, with a significant de-escalation from radical mastectomies to the current paradigm of breast conserving surgery (BCS) and neoadjuvant chemotherapy (NACT). We aimed to appraise the literature regarding the feasibility of de-escalation of treatment of axillary disease in the context of NACT. MATERIALS AND METHODS: We appraised studies and guidelines published regarding this topic and discussed them in this mini-review. RESULTS AND CONCLUSION: The SNB following NACT is oncologically safe in patients with clinically node negative disease and in patients with biopsy proven axillary node involvement at presentation provided that the dual technique is used and the clipped pathological node is harvested.


Assuntos
Axila/cirurgia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar/efeitos adversos , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Metástase Linfática , Mastectomia Radical/efeitos adversos , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela
7.
Anticancer Res ; 40(10): 5379-5391, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988857

RESUMO

BACKGROUND/AIM: Hypoxia-inducible factor 1 (HIF1) inhibitors have been proposed as therapeutic agents for several tumor types. HIF1α is induced by hypoxia and by pathogens in normoxia through toll-like receptors (TLRs). The TLR3 activator polyinosinic:polycytidylic acid [poly(I:C)] induces apoptosis in various types of cancer but not in the most aggressive breast cancer cell lines. We hypothesized that the failure of TLR3 stimulation to induce apoptosis in these cells might be due to an elevated HIF1α level and this link might be exploited. MATERIALS AND METHODS: Poly(I:C)-induced signaling pathway and expression of HIF1α and HIF1α targets were studied in MDA MB-231 and MCF-7 breast cancer cell lines by western blot. Flow cytometry was used for apoptotic responses and vasculogenic mimicry as bioassay. RESULTS: Poly(I:C) increased expression of HIF1α and its targets BCL2 apoptosis regulator and c-MYC. Moreover, using pharmacological or genetic HIF1 inhibition, reduction of poly(I:C)-induced expression of HIF1α was paralleled by lowering of c-MYC and increased sensitivity to poly(I:C)-induced apoptosis, demonstrating the crucial role of this factor. We provide the first evidence in breast cancer cells that TLR3 stimulation induces HIF1α-dependent vasculogenic mimicry. By using specific inhibitors, we identified a signaling cascade upstream of HIF1α induction. CONCLUSION: Combined treatment with poly(I:C) and HIF1 inhibitors deserves consideration as an effective strategy in breast cancer therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Poli I-C/farmacologia , Receptor 3 Toll-Like/genética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Transdução de Sinais/efeitos dos fármacos , Receptor 3 Toll-Like/agonistas
8.
Isr Med Assoc J ; 9(22): 498-502, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954696

RESUMO

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Cardiotoxicidade/etiologia , Feminino , Humanos , Israel , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente
10.
Crit Rev Oncol Hematol ; 154: 103070, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32871325

RESUMO

Cancer is a heterogeneous disease, occurs due to transcriptional changes in genetic and epigenetic including numerous genes and proteins. Worldwide, breast cancer (BC) is the life-threatening malignancies in women, is characterized by the occurrence of more than one molecular alteration. The incidence and mortality of BC are growing every day because of the adoption of western living standards, metropolitanization, and more life expectancy. Even though many modern approaches are available for the detection and treatment of BC, despite of these, it remains the topmost cause of death in women. This review highlights various approaches, including the importance of clinical, pathological, and molecular aspects of BC. Moreover, risk factors, biomarkers, immunotherapy, investigational drugs, and their role through tumor targets and immune systems have been discussed for management of BC. Furthermore, various targeting approaches for tumors through nanocarriers and their clinical trials have been elaborated in BC challenges and future perspectives.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Drogas em Investigação , Feminino , Humanos , Imunoterapia
12.
Medicine (Baltimore) ; 99(38): e22331, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957402

RESUMO

Since 2013, trastuzumab emtansine (T-DM1) has been widely used in Japan to treat patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who were previously administered trastuzumab and a taxane. However, there is no information about the treatment outcomes after exposure to T-DM1 in Japanese patients with HER2-positive MBC. In this study, we aimed to describe the survival outcomes of patients with HER2-positive MBC who received a treatment following T-DM1 and clarify the predictive factors of their prognosis.We retrospectively identified patients with HER2-positive MBC who received T-DM1 between April 1, 2014, and December 31, 2018, at the National Cancer Center Hospital, and focused on the population that received another line of therapy following T-DM1 discontinuation.Thirty patients were available for the outcome analysis. Median progression-free survival (PFS) of the first subsequent therapy was 6.0 months [95% confidence interval (95% CI) 4.1-6.4], whereas the median overall survival (OS) from the first subsequent therapy was 20.6 months (95% CI 13.5 months to not reached). We divided the patients into 2 groups according to their PFS with T-DM1 treatment and compared their PFS with the subsequent therapy. The results revealed a significant difference in the median PFS with the first subsequent treatment between patients with the PFS of less than and more than 3 months [5.1 (95% CI 1.7-6.2) vs 6.2 (95% CI 4.0-11.3) months, P = .03].This is the first study to evaluate the survival outcomes of post-T-DM1 therapy in Japanese patients with HER2-positive MBC. A short PFS with T-DM1 might affect the PFS with a treatment after T-DM1.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2 , Estudos Retrospectivos , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(38): e22228, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957363

RESUMO

INTRODUCTION: Cancer is the second leading cause of death, and the burden of cancer continues to grow globally. Research on the efficacy of combined administration of herbal medicine and anticancer drugs is also increasing. SH003 is a new herbal medicine composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. SH003 alone up to 4800 mg daily was found to be safe. Preclinical studies have shown SH003 to have a synergistic effect with coadministration of anticancer drugs. This study aimed to determine the maximum tolerated dose of SH003 combined with docetaxel in patients with lung or breast cancer. METHODS: This is an open-label, dose-escalation study to evaluate the safety of SH003 combined with docetaxel. Patients with lung or breast cancer will be recruited. The participants will be divided into 3 groups based on SH003 daily dose (2400, 3600, and 4800 mg); the medication will be taken orally for 21 days. The traditional 3 + 3 design will be adopted for the dose escalation. Dose-limiting toxicities are defined as grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events. The highest dose at which no more than 1 of the 6 patients experience dose-limiting toxicity will be determined as the maximum tolerated dose of SH003 combined with docetaxel. DISCUSSION: This study investigates the safety of SH003 when combined with docetaxel. The results of this study will provide a safe dose range for conducting therapeutic exploratory trials. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04360317.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Ensaios Clínicos Fase I como Assunto , Humanos , Fitoterapia
14.
Anticancer Res ; 40(9): 4829-4841, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878771

RESUMO

Most breast cancers express the estrogen receptor (ER) receptor and are negative for the human epidermal growth factor receptor 2 (HER2) receptor. ER+/HER2- cancers are treated with hormone-based therapies in the adjuvant setting and derive significant survival benefit from these therapies in the metastatic setting. However, hormone resistance develops in most metastatic patients. An increased understanding of the biology of ER+/HER2- breast cancers has led to the development of new therapies for this disease including CDK4/6 inhibitors and PI3K inhibitors. Several other neoplastic processes are targeted by novel drugs in clinical development, addressing cancer vulnerabilities. These include newer ways to block the ER and targeting the HER2 receptors in ER+/HER2- cancers expressing HER2 in low levels not qualifying for clinical positivity. In addition, promising therapeutic options include targeting other surface receptors or their downstream pathways, as well as targeting the apoptotic machinery and boosting the immune response which is initially insufficient in these cancers. A selection of new drugs in advanced development for ER+/HER2- breast cancer will be discussed in this review.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Mutação , Fosfatidilinositol 3-Quinases/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptores Estrogênicos/antagonistas & inibidores , Receptores Estrogênicos/genética , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Anticancer Res ; 40(9): 5229-5235, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878811

RESUMO

BACKGROUND/AIM: The prolactin receptor (PRLR) is implicated in the tumorigenesis of breast and prostate cancers where it drives cell proliferation, survival, and migration. LFA102 is a humanized monoclonal antibody against PRLR with promising preclinical antitumor activity. To determine the maximum tolerated dose or a recommended dose, and to delineate the pharmacokinetic profile of LFA102 in Japanese patients, we conducted a phase I study. PATIENTS AND METHODS: LFA102 was intravenously infused every 4 weeks to patients with advanced breast or castration-resistant prostate cancer, and the dose increased from 3 to 40 mg/kg. RESULTS: Fourteen patients were treated, and toxicities were reported in 9 (64%) patients. They were all grade 1 or 2, and the most frequently observed toxicity was nausea (3 patients, 21%). No dose-limiting toxicities were observed. LFA102 did not show antitumor activity as a single agent. CONCLUSION: Treatment with LFA102 was well tolerated.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/mortalidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias de Próstata Resistentes à Castração/etiologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
16.
Anticancer Res ; 40(10): 5641-5647, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988888

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have gained remarkable attention because of their ability to dualistically regulate tumor growth. The main objective of this study was to evaluate the apoptotic effects of human bone marrow-derived (hBM) MSCs in combination with interferon gamma (IFN-γ) on MCF-7 breast cancer cells, and to determine the cytokines involved in the apoptotic process. MATERIALS AND METHODS: hBM-MSCs were co-cultured with MCF-7 cells either directly and indirectly for 72 h in-vitro. Levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), apoptosis and cytokines were analyzed. RESULTS: hBM-MSCs increased the apoptosis of MCF-7 cells partially through TRAIL in vitro. IFN-γ enhanced the apoptotic effect of hBM-MSCs (p<0.001). CONCLUSION: hBM-MSCs in combination with IFN-γ might be a suitable therapy for breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Interferon gama/farmacologia , Células-Tronco Mesenquimais/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Técnicas de Cocultura , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/genética , Células MCF-7 , Células-Tronco Mesenquimais/citologia
17.
Anticancer Res ; 40(10): 5883-5893, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988919

RESUMO

BACKGROUND/AIM: Somatic mutations were investigated in 21 patients with postmenopausal estrogen receptor (ER)-positive and human epidermal growth factor receptor-2 (HER-2)-positive (ER+HER2+) breast cancer (BC) treated with neoadjuvant letrozole and lapatinib, to identify their distinct molecular landscape. PATIENTS AND METHODS: We used tissue samples of 21 patients from phase II Neo ALL-IN cohort, and somatic alterations were examined using targeted exome sequencing performed in Foundation Medicine, Inc. (FMI). RESULTS: TP53 (61.9%) and PIK3CA (57.1%) were the two most frequently mutated genes that were inter-correlated (p=0.026). They were associated with unfavorable clinical outcomes, particularly when accompanying PIK3CA mutations at exon 9 in helical domains. Meanwhile, MLL2 alteration was negatively associated with mutations of TP53 or PIK3CA, and it tended to be present in patients with low KI-67 levels and no initial nodal involvement. Moreover, patients with MLL2 mutations numerically showed more favorable overall response rates (ORR) (80% vs. 56.2%) and better 5-year event-free survival (EFS) rates (100% vs. 87.5%) compared to the wild-type. CONCLUSION: Mutations in TP53 and PIK3CA hotspot at exon 9 may be potential negative predictors of ER+HER2+ BC treated with neoadjuvant letrozole and lapatinib, while MLL2 inactivating mutation might confer therapeutic benefit in these patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Idoso , Biomarcadores Tumorais/genética , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lapatinib/administração & dosagem , Letrozol/administração & dosagem , Pessoa de Meia-Idade , Mutação/genética , Intervalo Livre de Progressão , Receptor ErbB-2/genética
18.
Medicine (Baltimore) ; 99(33): e21695, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872042

RESUMO

BACKGROUND AND OBJECTIVES: Chemotherapy does not only affect cancer cells; it also affects, to a greater or lesser degree, all other cells in the body. This toxicity should be assessed according to its severity, frequency, and duration, taking into account objective and subjective dimensions in its assessment. This assessment is a highly relevant aspect when providing care to chemotherapy patients, mainly due to the impact of the treatment on the patient's quality of life, as well as the vital risk it may imply under certain circumstances. For all this, the objective of this study was to assess the relationship between chemotherapy-associated adverse reactions and health-related quality of life in breast cancer patients. MATERIALS AND METHODS: With this purpose, a descriptive cross-sectional study was developed on 110 breast cancer patients who were treated with docetaxel, epirubicin, and cyclophosphamide. RESULTS: It is worth highlighting the negative effect of nausea, dysgeusia, peripheral neuropathy, loss of appetite, myalgia, and peripheral edema on the quality of life. Likewise, it is worth mentioning peripheral neuropathy as the toxicity that affects a greater number of quality-of-life indicators. CONCLUSIONS: To sum up, it would be necessary to make health professionals aware of the importance of chemotherapy-associated adverse reactions.


Assuntos
Atividades Cotidianas/psicologia , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Neoplasias da Mama/psicologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
19.
Bull Cancer ; 107(10): 1019-1023, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32972763

RESUMO

In this review, we report a case of a bone's metastatic breast cancer in Malian patient treated by chemotherapy in whom SRAS-COV-2's diagnosis was made 9days after the onset gastrointestinal symptoms. Patient quickly died before any COVID-19's treatment. According to the poor outcomes of cancer patients with COVID-19, authors emphasize to an intensive attention to such patients in order to find the best therapeutic balance between the two pathologies during this pandemic.


Assuntos
Betacoronavirus , Neoplasias da Mama/complicações , Carcinoma Ductal de Mama/secundário , Infecções por Coronavirus/complicações , Diarreia/etiologia , Pandemias , Pneumonia Viral/complicações , Neoplasias da Coluna Vertebral/secundário , Vômito/etiologia , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/complicações , Carcinoma Ductal de Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Evolução Fatal , Feminino , Infecções por HIV/complicações , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/tratamento farmacológico , Tomografia Computadorizada por Raios X , Ácido Zoledrônico/uso terapêutico
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