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1.
Clin Cancer Res ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615719

RESUMO

PURPOSE: This phase II study determined the efficacy of lacnotuzumab added to gemcitabine plus carboplatin (gem-carbo) in patients with advanced triple-negative breast cancer (TNBC). EXPERIMENTAL DESIGN: Female patients with advanced TNBC, with high levels of tumor-associated macrophages, and not amenable to curative treatment by surgery or radiotherapy, were enrolled. Lacnotuzumab was dosed at 10 mg/kg every 3 weeks (Q3W), {plus minus} a dose on Cycle 1, Day 8. Gem and carbo were given at 1000 mg/m2 and area under curve 2 dose in mg, respectively, Q3W. Treatment continued until unacceptable toxicity, disease progression, or discontinuation by physician/patient. RESULTS: Patients received lacnotuzumab+gem-carbo (n=34) or gem-carbo (n=15). Enrollment was halted due to recruitment challenges owing to rapid evolution of the therapeutic landscape; formal hypothesis testing of the primary endpoint, was therefore not performed. Median progression-free survival was 5.6 months (90% CI: 4.47, 8.64) in the lacnotuzumab+gem-carbo arm and 5.5 months (90% CI: 3.45, 7.46) in the gem-carbo arm. Hematologic adverse events were common in both treatment arms; however, patients treated with lacnotuzumab experienced more frequent aspartate aminotransferase, alanine aminotransferase, and creatine kinase elevations. Pharmacokinetic results showed that free lacnotuzumab at 10 mg/kg exhibited a typical IgG pharmacokinetic profile and target engagement of circulating CSF-1 ligand. CONCLUSIONS: Despite successful target engagement and anticipated pharmacokinetic profile, lacnotuzumab+gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this manuscript would be informative for future studies testing agents targeting the CSF-1-CSF-1R pathway in TNBC.

2.
Adv Ther ; 38(12): 5752-5762, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34699004

RESUMO

INTRODUCTION: Concurrent anthracycline and taxane is an effective and efficient way to deliver neoadjuvant chemotherapy for HER2-negative breast cancers. Data on efficacy and tolerance to 6 cycles of concurrent docetaxel, epirubicin, and cyclophosphamide (TEC) is limited. METHOD: All patients with HER2-negative breast cancers who received neoadjuvant TEC from January 2013 to December 2019 were reviewed. RESULTS: A total of 71 patients [57 luminal B disease; 14 triple negative breast cancer (TNBC)] received neoadjuvant TEC with prophylactic granulocyte colony-stimulating factor (G-CSF). The pathological complete response (pCR) rate was 26.3% and 28.6% for luminal B and TNBC, respectively. With median follow-up of 48.9 months, 3 years disease-free survival was 85.9%, and 3 years overall survival was 89.6%. Non-hematological toxicities were common but the majority was grade 1 or 2. The most common grade 3 or 4 toxicity were hematological, including neutropenia (26.8%) and anemia (15.5%). There was no cardiotoxicity observed. Half of the patients had at least one dose reduction but all patients completed the planned 6 cycles and had breast surgery done. CONCLUSION: Six cycles of TEC with prophylactic G-CSF is an effective and tolerable neoadjuvant regime for HER2-negative breast cancers. Hematological toxicities were the most common toxicities. Although many patients required dose reduction, all patients completed treatment and there was no observed cardiotoxicity.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Epirubicina , Feminino , Humanos , Terapia Neoadjuvante , Receptor ErbB-2/uso terapêutico , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
3.
Breast Cancer Res Treat ; 189(3): 665-676, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34553296

RESUMO

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Capecitabina/uso terapêutico , Feminino , Humanos , Lapatinib/uso terapêutico , Quinolinas , Receptor ErbB-2/genética , Resultado do Tratamento
4.
Am J Cancer Res ; 11(8): 3921-3934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522458

RESUMO

The causal relationship between body mass index (BMI) and type 2 diabetes (T2D) and breast cancer prognosis is still ambiguous. The aim of this study was to investigate the prognostic effect of BMI and T2D on breast cancer disease-free survival (DFS) among Asian individuals. In this two-sample Mendelian randomization (MR) study, the instrumental variables (IVs) were identified using a genome-wide association study (GWAS) among 24,000 participants in the Taiwan Biobank. Importantly, the validity of these IVs was confirmed with a previous large-scale GWAS (Biobank Japan Project, BBJ). In this study, we found that a genetic predisposition toward higher BMI (as indicated by BMI IVs, F = 86.88) was associated with poor breast cancer DFS (hazard ratio [HR] = 6.11; P < 0.001). Furthermore, higher level of genetically predicted T2D (as indicated by T2D IVs) was associated with an increased risk of recurrence of and mortality from breast cancer (HR = 1.43; P < 0.001). Sensitivity analyses, including the weighted-median approach, MR-Egger regression, Radial regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) supported the consistency of our findings. Finally, the causal relationship between BMI and poor breast cancer prognosis was confirmed in a prospective cohort study. Our MR analyses demonstrated the causal relationship between the genetic prediction of elevated BMI and a greater risk of T2D with poor breast cancer prognosis. BMI and T2D have important clinical implications and may be used as prognostic indicators of breast cancer.

5.
Cancers (Basel) ; 13(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34439348

RESUMO

The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.

6.
JNCI Cancer Spectr ; 5(4): pkab060, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34377936

RESUMO

Background: The cost-effectiveness of mammography screening among Chinese women remains contentious. Here, we characterized breast cancer (BC) epidemiology in Hong Kong and evaluated the cost-effectiveness of personalized risk-based screening. Methods: We used the Hong Kong Breast Cancer Study (a case-control study with 3501 cases and 3610 controls) and Hong Kong Cancer Registry to develop a risk stratification model based on well-documented risk factors. We used the Shanghai Breast Cancer Study to validate the model. We considered risk-based programs with different screening age ranges and risk thresholds under which women were eligible to join if their remaining BC risk at the starting age exceeded the threshold. Results: The lifetime risk (15-99 years) of BC ranged from 1.8% to 26.6% with a mean of 6.8%. Biennial screening was most cost-effective when the starting age was 44 years, and screening from age 44 to 69 years would reduce breast cancer mortality by 25.4% (95% credible interval [CrI] = 20.5%-29.4%) for all risk strata. If the risk threshold for this screening program was 8.4% (the average remaining BC risk among US women at their recommended starting age of 50 years), the coverage was 25.8%, and the incremental cost-effectiveness ratio (ICER) was US$18 151 (95% CrI = $10 408-$27 663) per quality-of-life-year (QALY) compared with no screening. The ICER of universal screening was $34 953 (95% CrI = $22 820-$50 268) and $48 303 (95% CrI = $32 210-$68 000) per QALY compared with no screening and risk-based screening with 8.4% threshold, respectively. Conclusion: Organized BC screening in Chinese women should commence as risk-based programs. Outcome data (e.g., QALY loss because of false-positive mammograms) should be systemically collected for optimizing the risk threshold.

7.
Patient Educ Couns ; 2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34023175

RESUMO

OBJECTIVE: To explore the dietary practices and decision-making process among Chinese breast cancer (BCA) survivors. METHODS: Using a grounded theory approach, this qualitative study involved individual semi-structured interviews with 30 BCA survivors. All interviews were audio-recorded and transcribed verbatim for analysis. RESULTS: Most of the participants reported making long-term diet modification. Key themes were grouped into three stages: (1) Motivation, (2) Diet modification, and (3) Maintenance. Most participants reported to be motivated by cancer causal attributions formulated through the evaluation of past dietary habits. Others embarked on changes out of compliance to social expectations. BCA survivors interviewed were willing to make trade-offs for health, but also influenced by peer and traditional Chinese beliefs. The lack of awareness of dietary guidelines was a crucial barrier to adopting healthy eating. Lastly, maintenance of newly formed dietary habits was reinforced by positive feedback but hindered by a lack of both self-efficacy and social support. CONCLUSIONS: While the majority of BCA survivors expressed willingness to improve their diets, changes made were often inconsistent with existing dietary recommendations. PRACTICE IMPLICATIONS: Future interventions may target factors at different decision-making stages: guiding evaluation of past diet, building self-efficacy and giving approval to encourage maintenance of healthy dietary behaviors.

8.
Chin Clin Oncol ; 10(3): 27, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34044545

RESUMO

BACKGROUND: The ACOSOG Z0011 trial demonstrated safe omission of axillary lymph node dissection (ALND) in patients with one or two positive sentinel lymph nodes (SLNs) receiving breast conservative surgery, followed by whole breast irradiation and adjuvant systemic treatment. This study aims to evaluate the exportability of the ACOSOG Z0011 criteria in an Asian/Chinese cohort residing in Hong Kong. METHODS: Retrospective analysis of a prospectively maintained database in a University affiliated tertiary breast centre was performed from June 2014 to May 2019. All breast cancer patients with no palpable adenopathy before surgery, one or more positive sentinel lymph nodes on histological examination and no prior neoadjuvant systemic treatment were recruited. Patients were grouped as eligible or ineligible according to the ACOSOG Z0011 criteria. The eligible group was compared with the sentinel alone group in the ACOSOG Z0011 cohort. RESULTS: Two hundred and forty-eight patients were recruited into the study. Sixty patients (24%) met the ACOSOG Z0011 criteria and could potentially avoid ALND. A higher percentage of clinical T2 tumors were observed in our eligible group than in the ACOSOG Z0011 trial (P=0.002). The histological subtype, tumor grade, estrogen receptor (ER)/progestogen receptor (PR) status and lymphovascular invasion status did not differ. There was no statistically significant difference in the proportion of SLN micrometastasis and macrometastasis between the two groups. CONCLUSIONS: This study demonstrated clinical similarities between our eligible cohort and the ACOSOG Z0011 cohort, which confirms exportability of the ACOSOG Z0011 criteria to a subset of population in Hong Kong.


Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/cirurgia , Feminino , Hong Kong , Humanos , Linfonodos , Metástase Linfática , Estudos Retrospectivos
9.
Breast Cancer Res Treat ; 188(2): 449-458, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33909203

RESUMO

PURPOSE: To characterize health-related quality of life (HRQoL) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) from the NALA phase 3 study. METHODS: In NALA (NCT01808573), patients were randomized 1:1 to neratinib + capecitabine (N + C) or lapatinib + capecitabine (L + C). HRQoL was assessed using seven prespecified scores from the European Organisation for Research and Treatment of Cancer Quality Of Life Questionnaire core module (QLQ-C30) and breast cancer-specific questionnaire (QLQ-BR23) at baseline and every 6 weeks. Descriptive statistics summarized scores over time, mixed models evaluated differences between treatment arms, and Kaplan-Meier methods were used to assess time to deterioration in HRQoL scores of ≥ 10 points. RESULTS: Of the 621 patients randomized in NALA, patients were included in the HRQoL analysis if they completed baseline and at least one follow-up questionnaire. The summary, global health status, physical functioning, fatigue, constipation, and systemic therapy side effects scores were stable over time with no persistent differences between treatment groups. There were no differences in time to deterioration (TTD) for the QLQ-C30 summary score between treatment arms; the hazard ratio (HR) for N + C vs. L + C was 0.94 (95% CI 0.63-1.40). Only the diarrhea score worsened significantly more in the N + C arm as compared to the L + C arm, and this remained over time (HR for TTD for N + C vs. L + C was 1.71 [95% CI 1.32-2.23]). CONCLUSION: In NALA, patients treated with N + C maintained their global HRQoL over time, despite a worsening of the diarrhea-related scores. These results may help guide optimal treatment selection for HER2-positive MBC.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Capecitabina/efeitos adversos , Feminino , Humanos , Quinolinas , Receptor ErbB-2/genética
10.
Breast Cancer Res Treat ; 187(3): 759-768, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33860389

RESUMO

PURPOSE: In the KATHERINE study (NCT01772472), patients with HER2-positive early breast cancer (EBC) and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy who were treated with adjuvant trastuzumab emtansine (T-DM1) had a 50% reduction in the risk of an invasive disease-free survival (IDFS) event compared to patients treated with adjuvant trastuzumab. In metastatic disease, T-DM1 has resulted in higher rates of thrombocytopenia in Asian versus non-Asian patients. Here, we report safety and efficacy in Chinese patients from KATHERINE. METHODS: Patients with HER2-positive EBC and residual invasive disease after taxane- and trastuzumab-containing neoadjuvant chemotherapy followed by surgery were randomized 1:1 to 14 cycles of adjuvant T-DM1 or trastuzumab. The primary endpoint was time to an IDFS event. RESULTS: Among Chinese patients (T-DM1 n = 51, trastuzumab n = 50), T-DM1 treatment resulted in a 43% reduction in risk of an IDFS event compared to trastuzumab (HR = 0.57; 95% CI 0.25-1.31), with similar results for secondary endpoints. As in the global population, Chinese patients receiving T-DM1 versus trastuzumab had more grade ≥ 3 adverse events (AEs; 39.2% versus 4.1%) and AEs leading to treatment discontinuation (27.5% versus 0%). The most common grade ≥ 3 AE with T-DM1 was thrombocytopenia (21.6%), a frequency higher than the frequency in the global population (5.7%). Grade ≥ 3 hemorrhage was reported in 1 patient (T-DM1 arm). CONCLUSIONS: In the KATHERINE study, T-DM1 demonstrated increased efficacy compared to trastuzumab in Chinese patients. Consistent with previous data in Asian patients, T-DM1 was associated with more grade ≥ 3 AEs, and AEs leading to discontinuation, which was driven by an increase in thrombocytopenia.


Assuntos
Neoplasias da Mama , Maitansina , Ado-Trastuzumab Emtansina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , China , Feminino , Humanos , Maitansina/efeitos adversos , Terapia Neoadjuvante , Receptor ErbB-2/genética , Trastuzumab/efeitos adversos
11.
J Community Genet ; 12(3): 431-438, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33928521

RESUMO

Limited studies have examined the pre-counselling knowledge and attitudes of high-risk women on hereditary breast and ovarian cancer (HBOC) syndromes genetic screening in Asia Pacific regions, particularly among Chinese. After controlling cost, an intrinsic barrier to undertake such screening, comprehensive understanding of the baseline characteristics of this cohort towards HBOC genetic counselling and testing service (GT) could be sought. This study aimed at exploring the baseline knowledge, possible motivators, barriers, and decisional factors of undertaking such service. One hundred and forty-two Southern Hong Kong Chinese high-risk females (89.4% with cancer history; 10.6% were cancer-free at-risk family members) completed a questionnaire right before their pre-testing GT. Results showed that perceived benefits to self and family members with reference to cancer prevention are important decisional motivators. A sponsored cancer genetic testing service in this cohort was crucial as 71.3% would not have opted for self-financed screening. Pre-testing and post-testing counselling were essential, particularly for older and less educated high-risk individuals. More importantly, after thorough pre-counselling with Q&A session, the entire cohort in this study gave written consent to undertake GT. Moreover, those proven to be germline pathogenic variant carriers were willing to share the information with family members and successfully persuaded them to pursue GT.

12.
Breast Cancer Res Treat ; 186(3): 607-615, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33611665

RESUMO

BACKGROUND: Marking of cytology-proven metastatic axillary lymph node in breast cancer patients before neoadjuvant treatment and its subsequent surgical retrieval have been shown to reduce the false-negative rate of sentinel lymph node biopsy. A systematic review was performed to evaluate different strategies in nodal marking and localization. METHODS: PubMed, Embase, EBSCOhost, and the Cochrane library literature databases were searched systematically to address the identification rate and retrieval rate of marked axillary lymph nodes. Studies were eligible if they performed nodal marking before neoadjuvant treatment, followed by selective extirpation of these marked axillary lymph nodes in definitive surgery RESULTS: Fifteen studies with a total of 703 patients were included. Index axillary lymph nodes were marked by clips or tattooed prior to the commencement of neoadjuvant treatment. In our pooled analysis, eighty-eight percent of the clipped nodes and ninety-seven percent of the tattooed nodes were successfully retrieved. Among these patients, seventy-seven percent of these marked axillary lymph nodes were also sentinel lymph nodes. CONCLUSION: Marking and selectively removing cytology-proven metastatic axillary lymph nodes after neoadjuvant treatment is feasible. An acceptably high nodal retrieval rate could be achieved using various methods of nodal marking and localization techniques.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela
14.
Jpn J Clin Oncol ; 51(3): 345-353, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33619550

RESUMO

BACKGROUND: The addition of pertuzumab to trastuzumab plus standard chemotherapy as adjuvant therapy following surgery significantly improved invasive disease-free survival (IDFS) in patients with HER2-positive early breast cancer in the multinational randomized APHINITY trial (NCT01358877, BIG 4-11/BO25126/TOC4939G). We analyzed clinical outcomes in the subgroup of patients recruited at Chinese sites. METHODS: Patients were randomized to standard adjuvant chemotherapy plus 1 year of trastuzumab with pertuzumab or placebo. Patients recruited in mainland China, Hong Kong and Taiwan are included in this descriptive analysis. RESULTS: Chinese patients had similar demographic characteristics to the global population, but a higher proportion had nodal involvement. Although this subgroup analysis was not powered to detect statistical significance, a numerical improvement in IDFS was observed with the addition of pertuzumab to trastuzumab in Chinese patients (hazard ratio, 0.69; 95% confidence interval: 0.39-1.19; 3-year IDFS event-free estimates 92.5% [pertuzumab] and 91.7% [placebo]), which was consistent with the primary analysis of the global population. Further subgroup analyses showed numerical improvements in the Chinese node-positive, hormone receptor-negative and -positive subgroups, although confidence intervals were wide due to the low number of events. The incidence of diarrhea was higher in the pertuzumab arm, and no primary cardiac events occurred in Chinese patients in either arm. CONCLUSIONS: Pertuzumab, used in combination with trastuzumab and chemotherapy in APHINITY, is effective as an adjuvant treatment regimen for Chinese patients with HER2-positive early breast cancer in a setting with curative intent. The safety profile in Chinese patients was consistent with that of the global population.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China , Intervalo Livre de Doença , Determinação de Ponto Final , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Trastuzumab/efeitos adversos , Trastuzumab/farmacologia , Resultado do Tratamento
15.
J Evid Based Med ; 14(2): 97-111, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33565274

RESUMO

OBJECTIVE: Recommendations for widespread use of face mask, including suggested type, should reflect the current published evidence and concurrently be studied. This review evaluates the preclinical and clinical evidence on use of cloth and surgical face masks in SARS-CoV-2 transmission and proposes a trial to gather further evidence. METHODS: PubMed, EMbase, and the Cochrane Library were searched. Studies of SARS-CoV-2 and face masks and randomized controlled trials (RCTs) of n ≥ 50 for other respiratory illnesses were included. RESULTS: Fourteen studies were included in this study. One preclinical and 1 observational cohort clinical study found significant benefit of masks in limiting SARS-CoV-2 transmission. Eleven RCTs in a meta-analysis studying other respiratory illnesses found no significant benefit of masks (±hand hygiene) for influenza-like-illness symptoms nor laboratory confirmed viruses. One RCT found a significant benefit of surgical masks compared with cloth masks. CONCLUSION: There is limited available preclinical and clinical evidence for face mask benefit in SARS-CoV-2. RCT evidence for other respiratory viral illnesses shows no significant benefit of masks in limiting transmission but is of poor quality and not SARS-CoV-2 specific. There is an urgent need for evidence from randomized controlled trials to investigate the efficacy of surgical and cloth masks on transmission of SARS-CoV-2 and user reported outcomes such as comfort and compliance.


Assuntos
COVID-19/prevenção & controle , Máscaras , Pneumonia Viral/prevenção & controle , Têxteis , COVID-19/transmissão , Humanos , Pandemias , Pneumonia Viral/transmissão , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/transmissão , Infecções Respiratórias/virologia , SARS-CoV-2
16.
Int J Mol Sci ; 22(2)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477375

RESUMO

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Neoplasias Ovarianas/genética , Proteína BRCA1/metabolismo , Neoplasias da Mama/metabolismo , Anemia de Fanconi/genética , Feminino , Genes BRCA1 , Predisposição Genética para Doença , Células Germinativas , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Linhagem
17.
Pediatr Res ; 89(5): 1245-1252, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32634817

RESUMO

BACKGROUND: We investigated whether plasma high-sensitivity cardiac troponin T (hs-cTnT) and circulating heart-associated microRNA (miRs) are increased in children with leukaemias during anthracycline-based chemotherapeutic treatment. METHODS: In vitro human pluripotent stem cell (hPSC)-derived cardiomyocyte model showed that miR-1, miR-133a, miR-208a, miR-208b, and miR-499 are released from cells into culture medium in a time- and dose-dependent manner on doxorubicin exposure. Left ventricular (LV) myocardial deformation and circulating heart-associated miRs and plasma hs-cTnT during and after completion of chemotherapy were determined in 40 children with newly diagnosed acute leukaemia. RESULTS: Significant reduction of LV global longitudinal strain and strain rates were found within 1 week after completion of anthracycline therapy in the induction phase of treatment (all p < 0.05). Hs-cTnT level peaked and miR-1 increased significantly at this time point. Log-transformed hs-cTnT correlated negatively with LV global systolic longitudinal strain (r = -0.38, p < 0.001). Receiver operating characteristic analysis revealed that area under the curve for changes in plasma hs-cTnT from baseline and plasma miR-1 levels in detecting a reduction in ≥20% of global longitudinal strain were respectively 0.62 (95% CI 0.38-0.87) and 0.62 (95% CI 0.40-0.84). CONCLUSION: Plasma hs-cTnT and circulating miR-1 may be useful markers of myocardial damage during chemotherapy in children with leukaemias. IMPACT: Heart-associated miRNAs including miR-1, miR-133a, miR-208a, miR-208b,and miR-499 were increased in the culture medium upon exposure of hPSC-derived cardiomyocytes to doxorubicin. Only miR-1 increased significantly during anthracycline-based therapy in paediatric leukaemic patients. In paediatric leukaemic patients, plasma hs-cTnT and circulating level of miR-1 showed the most significant increase within 1 week after completion of anthracycline therapy in the induction treatment phase. The study provides the first evidence of progressive increase in circulating miR-1 and plasma hs-cTnT levels during the course of anthracycline-based therapy in children with leukaemias, with hs-cTnT level also associated with changes in LV myocardial deformation.

18.
Cancer Treat Res Commun ; 26: 100241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33340904

RESUMO

INTRODUCTION: Several ongoing trials are currently investigating the feasibility and non-inferiority of active surveillance for managing low-risk DCIS. However, little is known on the proposed non-surgical treatment for DCIS from patient's perspective. METHODS: A prospective cohort study was performed on 1000 consecutive patients aged 18 to 90 years old with various breast disorders between 1st July 2019 and 31st December 2019. Patients were asked about their opinions on non-surgical treatments for DCIS after thorough explanation of the clinical scenario. RESULTS: Median age was 55 years old (Range 18 - 87). 692 patients had past history of breast cancer, 279 patients had benign breast conditions, 29 patients had borderline breast lesions. 891 (89.1%) patients opted for standard surgical excision for low-risk DCIS, most of them (N = 757, 85.0%) decided for operative management for DCIS to avoid life-time anxiety of disease progression. Patients of older age and with history of malignant breast conditions are more likely to choose surgical treatment for DCIS (p<0.0001). Of note, 112 (11.2%) patients in the cohort had history of DCIS with excision done, 111 (99.1%) patients would still decide for surgical excision as the treatment of DCIS, only 1 patient expressed the wish for conservative treatment for DCIS. CONCLUSION: Majority of patients decided for surgical treatment for DCIS despite being offered the condition that conservative treatment could be oncologically safe. Patient anxiety and cost of extensive breast surveillance are two important factors.

19.
BMC Cancer ; 20(1): 1053, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138793

RESUMO

BACKGROUND: Germline TP53 mutations are associated with Li-Fraumeni syndrome, a severe and rare hereditary cancer syndrome. Despite the rarity of germline TP53 mutations, the clinical implication for mutation carriers and their families is significant. The risk management of TP53 germline mutation carriers is more stringent than BRCA carriers, and radiotherapy should be avoided when possible. METHODS: TP53 gene mutation screening was performed in 2538 Chinese breast cancer patients who tested negative for BRCA mutations. RESULTS: Twenty TP53 mutations were identified with high next-generation sequencing concerning for germline mutations in Chinese breast cancer families. The majorities of the TP53 carriers had early-onset, hormone receptor-positive breast cancer, and had strong family history of cancer. Among all, 11 patients carried a germline mutation and 6 of which were likely de novo germline mutations. In addition, 1 case was suspected to be induced by chemotherapy or radiation, as this patient had no significant family history of cancer and aberrant clonal expansion can commonly include TP53 mutations. Furthermore, we have identified one mosaic LFS case. Two novel mutations (c.524_547dup and c.529_546del) were identified in patients with early-onset. CONCLUSIONS: In view of the high lifetime risk of malignancy, identification of patients with germline TP53 mutations are important for clinicians to aid in accurate risk assessment and offer surveillance for patients and their families.


Assuntos
Neoplasias da Mama/diagnóstico , Mutação em Linhagem Germinativa , Análise de Sequência de DNA/métodos , Proteína Supressora de Tumor p53/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
20.
Am J Cancer Res ; 10(9): 2865-2877, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042622

RESUMO

Cellular metabolism reprogramming is a hallmark in cancers including breast cancer. Switching off the glycolytic energy in cancer has been indicated as one of the anti-cancer strategies. Aberrant haptoglobin (HP) expression has been shown to cause metabolic dysfunction and implicated in different malignancies. However, its roles in breast cancer and glycolysis remain elusive. Here, we reported HP was upregulated in breast cancer tissues and the circulation. HP conferred oncogenic roles by regulating cell cycle progression and apoptosis in breast cancer cells. Further analysis identified the correlation between HP and glycolytic enzymes such as glucose-6-phosphate isomerase (GPI) and hexokinase (HK). Glycolytic activities were altered upon HP knockdown which were confirmed by glucose uptake and LDH activity assays. GPI was found to be downstream effector of HP while knockdown of GPI led to decreased glycolytic activity and restored oxygen consumption. GPI silencing decreased cell migration/invasion ability and sensitized breast cancer cells to chemo-drug. Moreover, animal study suggested inhibition of both HP and GPI significantly impeded tumor growth in mice. Collectively, we report for the first time the oncogenic roles of HP, at least partially, through regulating glycolysis and its downstream effector, GPI, contributes in maintaining EMT and chemoresistance in breast cancer.

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