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Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
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Humanos , Feminino , Neoplasias da Mama/induzido quimicamente , Paclitaxel/efeitos adversos , Lipossomos/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Trastuzumab/uso terapêutico , Capecitabina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Since trastuzumab was listed and approved for breast cancer in 2002, China has entered a new epoch of targeted therapy. Over the past 20 years, anti-human epidermal growth factor receptor 2 (HER2) targeted therapy for breast cancer in China has experienced the era of single-target, tyrosine kinase inhibitors, double-target and anti-HER2 plus antibody-drug conjugate. Advancement in the anti-HER2 targeted therapy is continuously changing the treatment mode of patients with HER2 positive status and even HER2 low expression, significantly improved their prognosis. In the past 20 years, Chinese scholars have participated in international clinical researches, completed a series of registration studies of imported drugs, developed new drugs with proprietary intellectual property rights, enriched the evidence of clinical research on HER2-targeted therapy, and formed a treatment system with both international standards and Chinese characteristics. In particular, the formulation of the Chinese Society of Clinical Oncology Breast Cancer Guidelines and the Chinese expert consensus on anti-HER2 targeted treatment in breast cancer are the concentrated embodiments of Chinese wisdom.
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Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Trastuzumab , Mama , Povo Asiático , ChinaRESUMO
With the development of new strategies like target therapy and immunotherapy, early breast cancer treatment has become more standardized, and the interval of disease free survival has been extended. Although guidelines and expert consensus have provided supports for clinical decision making, there are still some controversial issues in clinical practice, attributing to different treatment concepts, product indications and accessibility. These controversial issues would eventually affect the treatment of early breast cancer. This year in 2021, the approval of new indications of drugs like abemaciclib and the popularity of dual anti-human epidermal growth factor receptor 2 targeted drugs have promoted the change of treatment modalities for different types of early breast cancer. To this end, ten hot topics of early breast cancer are summarized according to their different molecular typing and treatment stages for discussion.
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Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Receptor ErbB-2/antagonistas & inibidoresRESUMO
OBJECTIVE@#To analyze the acupoint selection rules of acupuncture for pseudobulbar palsy dysphagia using data mining technology.@*METHODS@#The literature of acupuncture for pseudobulbar palsy dysphagia published from January 1, 1990 to May 1, 2021 was retrieved from CNKI, SinoMed, Wanfang, VIP, and PubMed databases. Acupuncture prescription database was established. The frequency of acupoint selection was analyzed by Microsoft Excel 2016; Apriori algorithm was used to analyze the association rules and draw the high-frequency acupoint co-occurrence network diagram; SPSS21.0 was used to perform clustering analysis.@*RESULTS@#A total of 87 literature was included, involving 89 acupuncture prescriptions and 71 acupoints. Fengchi (GB 20) was the most frequently-used acupoint; the commonly-selected meridians were gallbladder meridian, conception vessel, governor vessel and stomach meridian; the acupoints located at the neck were the most frequently-used acupoints; the crossing points were commonly selected among the special acupoints. The most commonly-used acupoint combination was Jinjin (EX-HN 12) plus Yuye (EX-HN 13).@*CONCLUSION@#The modern acupuncture for pseudobulbar palsy dysphagia usually selects local acupoints, especially the neck acupoints such as Fengchi (GB 20) and Lianquan (CV 23). The acupoints in the front and back are concurrently selected with needles towards the disease location.
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Humanos , Pontos de Acupuntura , Terapia por Acupuntura , Transtornos de Deglutição/terapia , Meridianos , Paralisia PseudobulbarRESUMO
Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.
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Feminino , Humanos , Aminopiridinas/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Consenso , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Quinase 6 Dependente de Ciclina/antagonistas & inibidoresRESUMO
Real-world study is increasingly becoming an important source of evidence for changing clinical practice, especially for clinical problems that can't be randomized. In recent years, real-world research in the field of breast cancer has gradually became a boom. Existing research results have begun to assist in the epidemiological analysis of breast cancer, promote the approval of rare diseases diagnosis and indication, and promote the analysis of real-world treatment status and evaluation of curative effects. Chinese scholars have also established databases and carried out relevant real-world research, providing real-world evidence for clinical practice in China. But domestic research is still in its infancy. The number of real-world research literature published by domestic scholars is relatively small, and there is a lack of pragmatic randomized clinical trial and real-world research for decision-making. In the future, we need to take advantage of the abundant diagnosis and treatment resources, further improve the database, and carry out real-world study on drug development based on population data in China.
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In the past two decades, with the introduction of NCCN guidelines, the establishment of a standardized diagnosis and treatment system for breast cancer had begun. The Chinese version of the NCCN guidelines, which combines international standards and Chinese characteristics, was then developed to guide clinical practice. Since 2011, Chinese experts have entered St. Gallen International Expert Consensus Group, and to introduce the latest therapy concepts. On this basis, the Chinese Society of Clinical Oncology has developed guidelines for diagnosis and treatment in line with product accessibility and expert opinions to help clinicians choose the best treatment option. The latest Chinese Society of Clinical Oncology Breast Cancer Guideline will further contribute to the establishment of a standardized diagnosis and treatment system for breast cancer.
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Increasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.
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In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients. Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m2, day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2 cycles. Both of the two patients achieved remarkable response with Partial Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15 ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and 60% respectively). The results indicate that regimen of pembrolizumab combination with albumin-bound paclitaxel might produce response in patients with HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy.
Assuntos
Paclitaxel Ligado a Albumina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Paclitaxel Ligado a Albumina/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Mama/diagnóstico por imagem , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Excisão de Linfonodo , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia MamáriaRESUMO
<p><b>BACKGROUND</b>The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA).</p><p><b>METHODS</b>From March 6, 2014 to December 10, 2014, 24 plasma samples from 20 patients with HER2-positive metastatic breast cancer who received systemic therapy were eligible. We used a panel for detection of hot-spot mutations from 50 oncogenes and tumor suppressor genes, and then used targeted next-generation sequencing (NGS) to identify somatic mutation of these samples in those 50 genes. Samples taken before their first trastuzumab administration and subsequently proven with clinical benefit were grouped into sensitive group. The others were collected after disease progression of the trastuzumab-based therapy and were grouped into the resistant group.</p><p><b>RESULTS</b>A total of 486 single-nucleotide variants from 46 genes were detected. Of these 46 genes, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), proto-oncogene c-Kit (KIT), and tumor protein p53 (TP53) were the most common mutated genes. Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred m utations in the resistant group were associated with the resistance of targeted therapy. In addition, we detected a HER2 S855I mutation in two patients who had persistent benefits from anti-HER2 therapy.</p><p><b>CONCLUSION</b>Targeted NGS of cfDNA has potential clinical utility to detect biomarkers from HER2-targeted therapies.</p>
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores Tumorais , Genética , Neoplasias da Mama , Genética , Metabolismo , Caderinas , Genética , Cromograninas , Genética , Classe I de Fosfatidilinositol 3-Quinases , Resistencia a Medicamentos Antineoplásicos , Genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP , Genética , Mutação , Genética , Fosfatidilinositol 3-Quinases , Genética , Proteínas Proto-Oncogênicas c-kit , Genética , Receptor ErbB-2 , Metabolismo , Receptor Notch1 , Genética , Proteína Supressora de Tumor p53 , GenéticaRESUMO
<p><b>OBJECTIVE</b>To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.</p><p><b>METHODS</b>A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed.</p><p><b>RESULTS</b>Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences.</p><p><b>CONCLUSIONS</b>The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Neoplasias da Mama , Tratamento Farmacológico , Metabolismo , Patologia , Hidrocarbonetos Aromáticos com Pontes , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Metástase Linfática , Terapia Neoadjuvante , Métodos , Modelos de Riscos Proporcionais , Receptor ErbB-2 , Metabolismo , Receptores de Estrogênio , Metabolismo , Receptores de Progesterona , Metabolismo , Indução de Remissão , Estudos Retrospectivos , Taxoides , Carga TumoralRESUMO
<p><b>OBJECTIVE</b>To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer.</p><p><b>METHODS</b>We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel.</p><p><b>RESULTS</b>The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the < 90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel < 75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who received >third line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021).</p><p><b>CONCLUSION</b>There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.</p>
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Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Antineoplásicos , Usos Terapêuticos , Neoplasias Ósseas , Tratamento Farmacológico , Neoplasias da Mama , Tratamento Farmacológico , Patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Seguimentos , Neoplasias Hepáticas , Tratamento Farmacológico , Neoplasias Pulmonares , Tratamento Farmacológico , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação , Taxoides , Usos TerapêuticosRESUMO
<p><b>BACKGROUND</b>Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.</p><p><b>METHODS</b>In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.</p><p><b>RESULTS</b>Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.</p><p><b>CONCLUSIONS</b>We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais Humanizados , Usos Terapêuticos , Antineoplásicos , Usos Terapêuticos , Bevacizumab , Neoplasias da Mama , Tratamento Farmacológico , Genética , Metabolismo , Hidrocarbonetos Aromáticos com Pontes , Usos Terapêuticos , Receptor ErbB-2 , Genética , Metabolismo , Taxoides , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.</p><p><b>METHODS</b>Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.</p><p><b>RESULTS</b>Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01).</p><p><b>CONCLUSIONS</b>The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.</p>
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Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Agranulocitose , Antimetabólitos Antineoplásicos , Usos Terapêuticos , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Neoplasias da Mama , Tratamento Farmacológico , Patologia , Capecitabina , Desoxicitidina , Usos Terapêuticos , Diarreia , Progressão da Doença , Intervalo Livre de Doença , Fluoruracila , Usos Terapêuticos , Seguimentos , Síndrome Mão-Pé , Leucopenia , Quimioterapia de Manutenção , Estadiamento de Neoplasias , Indução de Remissão , Estudos Retrospectivos , Taxoides , VimblastinaRESUMO
Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.
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Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Povo Asiático , Neoplasias da Mama , Tratamento Farmacológico , Genética , Metabolismo , Patologia , Capecitabina , Classe I de Fosfatidilinositol 3-Quinases , Desoxicitidina , Diarreia , Progressão da Doença , Intervalo Livre de Doença , Exantema , Fluoruracila , Síndrome Mão-Pé , Mutação , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases , Genética , Quinazolinas , Receptor ErbB-2 , Metabolismo , Indução de RemissãoRESUMO
<p><b>OBJECTIVE</b>To compare the efficiency of response evaluation by clinical examination, ultrasonograghy and mammography in neoadjuvant chemotherapy (NAC) for breast cancer.</p><p><b>METHODS</b>A retrospective cohort study was conducted to analyze the data of 141 patients treated with neoadjuvant chemotherapy. Response evaluation was performed by clinical palpation, ultrasound and mammography.</p><p><b>RESULTS</b>Only 12 (8.5%) among the 141 patients presented with a stage I tumor. The tumor size determined by palpation was often larger than that by ultrasound before therapy (P < 0.01). Among patients with suspicions axillary nodes checked by ultrasound, 88.3% (53/60) of them had positive nodes by pathology before NAC, and 34.5% (10/29) of patients with negative nodes determined by ultrasound had positive nodes by pathology. In all the 141 patients, 21(14.9%) showed pathological complete remission in both the primary tumor and lymph node. For response evaluation, the false complete remission rate judged by clinical examination was 46.8% (22/47), and the false tumor residual rate by ultrasound was 84.0% (21/25). In 53.5% (23/43) of patients the response could not be assessed by mammography due to that the tumors were undistinguishable in size. The range of microcalcification was not reduced in 5 patients with a partial response of the tumor. 25 patients experienced needle puncture during therapy. Among them, in the 9 pathologically negative patients, only 3 achieved pCR, and the other 16 positive patients didn't achieve pCR.</p><p><b>CONCLUSION</b>Using the puncture or sentinel lymph node biopsy, clinicians should pay enough emphasis on the pathological determination of the node status before chemotherapy. Clinicians will make a quite of false judgment of the tumor by clinical examination, ultrasound or mammography. They may use needle puncture during therapy to evaluate the response of neoadjuvant chemotherapy, and the result should be analyzed synthetically.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Axila , Neoplasias da Mama , Diagnóstico por Imagem , Tratamento Farmacológico , Patologia , Carcinoma Ductal de Mama , Diagnóstico por Imagem , Tratamento Farmacológico , Patologia , Quimioterapia Adjuvante , Estudos de Coortes , Linfonodos , Patologia , Metástase Linfática , Mamografia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Indução de Remissão , Métodos , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , UltrassonografiaRESUMO
<p><b>OBJECTIVE</b>To study the effects of exogenous ER beta on the growth of breast cancer MCF-7 cells under different treatment.</p><p><b>METHODS</b>An eukaryotic expression vector containing 1.6 kb of human entire coding sequence of ER beta (pCDNA3-ER beta) was transfected into human breast cancer MCF-7 cells using lipofectamine 2000. The biological activity of ER beta was detected with the luciferase reporter containing estrogen responsive element (ERE) and the expression of ER beta protein by Western blot. The growth properties of MCF-7, pCDNA 3-transfected MCF-7 and pCDNA 3-ER beta-transfected MCF-7 cells under different treatment, including E2 (17beta-estradiol) and 4-OHT (4-hydroxytamoxifen), were observed.</p><p><b>RESULTS</b>A stronger activation of the reporter by ER beta in the presence of E2 was observed in the pCDNA 3-ER beta-transfected MCF-7 cells than in the pCDNA 3-transfected MCF-7 and in MCF-7 cells. Western blot analysis showed that the protein level of ER beta in the pCDNA 3-ER beta-transfected MCF-7 cells was markedly increased. Exogenous ER beta expression did not change the growth properties and the morphology of MCF-7 cells under normal condition. The pCDNA 3-ER beta-transfected MCF-7 cells proliferated at the same rate as naive cells in the presence of 4-OHT, whereas a strong inhibition of the proliferation of the pCDNA 3-ER beta-transfected MCF-7 cells in the presence of E2 was observed.</p><p><b>CONCLUSION</b>Exogenous ER beta expression does not increase the resistance to 4-OHT, and a strong inhibition of the proliferation may occur in the presence of E2.</p>
Assuntos
Feminino , Humanos , Neoplasias da Mama , Metabolismo , Patologia , Linhagem Celular Tumoral , Proliferação de Células , Estradiol , Farmacologia , Antagonistas de Estrogênios , Farmacologia , Receptor beta de Estrogênio , Genética , Metabolismo , Tamoxifeno , Farmacologia , TransfecçãoRESUMO
<p><b>OBJECTIVE</b>To investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer.</p><p><b>METHODS</b>Of 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay.</p><p><b>RESULTS</b>Univariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P < 0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane.</p><p><b>CONCLUSION</b>ER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.</p>
Assuntos
Feminino , Humanos , Antineoplásicos Fitogênicos , Usos Terapêuticos , Neoplasias da Mama , Tratamento Farmacológico , Metabolismo , Patologia , Imuno-Histoquímica , Análise Multivariada , Estadiamento de Neoplasias , Paclitaxel , Usos Terapêuticos , Valor Preditivo dos Testes , Prognóstico , Receptor ErbB-2 , Metabolismo , Receptores de Estrogênio , Metabolismo , Indução de Remissão , Estudos Retrospectivos , Taxoides , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To investigate the expression of oncoprotein c-erbB2 in primary breast cancer and to analyze its relation to its prognosis.</p><p><b>METHODS</b>Immunohistochemical staining for c-erbB2 was performed on paraffin-embedded specimens of primary breast cancer from 284 patients, and the relation to its prognosis was statistically analyzed.</p><p><b>RESULTS</b>Positive expression rate of c-erbB2 was 26.8% (76/284) in 284 primary breast cancer patients. Expression of c-erbB2 was positively correlated with the status of lymph node metastasis (P = 0.003). Univariate analysis indicated that c-erbB2 expression is a significant prognostic factor for the disease-free survival (DFS) (P = 0.024) and overall survival (OS) (P = 0.002), while multivariate analysis demonstrated that c-erbB2 is an independent prognostic factor for OS (P = 0.023). Moreover, tumors with c-erbB2 positive expression are more tend to metastasis to other viscera than those with c-erbB2 negative. c-erbB2 expression has different prognostic values for patients with different status of estrogen receptor (ER) and lymph node metastasis.</p><p><b>CONCLUSION</b>c-erbB2 expression is an independent prognostic factor for total survival time in primary breast cancer patients, and its prognostic values are different according to the different ER status and lymph node metastasis.</p>
Assuntos
Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama , Metabolismo , Patologia , Terapêutica , Carcinoma Ductal de Mama , Metabolismo , Patologia , Terapêutica , Quimioterapia Adjuvante , Intervalo Livre de Doença , Seguimentos , Metástase Linfática , Mastectomia Radical , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Receptor ErbB-2 , Metabolismo , Receptores de Estrogênio , Metabolismo , Taxa de SobrevidaRESUMO
<p><b>OBJECTIVE</b>To investigate the effect and safety of zoledronic acid (Zoledex) in patients with cancer-induced hypercalcemia.</p><p><b>METHODS</b>Seventeen patients with cancer-induced hypercalcemia (corrected blood calcium > 2.70 mmol/L) were treated intravenously by 4 mg zoledex within 15 minutes on the first day. The corrected blood calcium was observed every 4 days in the following 28 days.</p><p><b>RESULTS</b>The response rate was 94.1% (16/17). The mean corrected blood calcium became normal after the first dose of zoledex (P < 0.01). The lowest value was found on the fourteenth day after treatment. The main side effects consisted of fever (29.4%, 5/17), hypocalcemic tetany (11.8%, 2/17) and arythmia (5.9%, 1/17).</p><p><b>CONCLUSION</b>Zoledex is effective and safe in the treatment of patient with cancer-induced hypercalcemia.</p>