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1.
J Public Health (Oxf) ; 40(2): 315-339, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28486650

RESUMO

Background: This review aimed to better understand experiences of being invited to cancer screening and associated decision-making. Methods: Qualitative evidence explaining UK cancer screening attendance decisions was systematically identified. Data were extracted and meta-ethnography used to identify shared themes, synthesize findings and generate higher level interpretations. Results: Thirty-four studies met inclusion criteria. They related to uptake of breast, cervical, colorectal, prostate, ovarian and lung cancer screening. Three primary themes emerged from the synthesis. 'Relationships with the health service' shaped decisions, influenced by trust, compliance with power, resistance to control or surveillance and perceived failures to meet cultural, religious and language needs. 'Fear of cancer screening' was both a motivator and barrier in different ways and to varying degrees. Strategies to negotiate moderate fear levels were evident. 'Experiences of risk' included the creation of alternative personal risk discourses and the use of screening as a coping strategy, influenced by disease beliefs and feelings of health and wellness. Conclusions: The findings highlight the importance of the provider-patient relationship in screening uptake and enrich our understanding of how fear and risk are experienced and negotiated. This knowledge can help promote uptake and improve the effectiveness of cancer screening.


Assuntos
Detecção Precoce de Câncer/psicologia , Idoso , Antropologia Cultural , Tomada de Decisões , Medo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Pesquisa Qualitativa , Reino Unido
2.
Crit Rev Oncol Hematol ; 110: 74-80, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28109407

RESUMO

Invasive breast cancer is the second most common cancer worldwide. It is known to metastasise to the regional axillary lymph nodes but there has been debate over what is the best way to stage and treat the axilla in patients presenting with primary breast cancer. Multiple trials over the last two decades have led to a change in practice from routine axillary lymph node dissection to sentinel lymph node biopsy in patients who are clinically lymph node negative preoperatively. This has resulted in new questions regarding subsequent treatment of some patients. This review will critically appraise the evidence on axillary treatment in patients with low burden axillary disease and highlight limitations of relevant randomised controlled trials.


Assuntos
Neoplasias da Mama/cirurgia , Linfonodos/cirurgia , Axila , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática , Ensaios Clínicos Controlados Aleatórios como Assunto , Biópsia de Linfonodo Sentinela
3.
Breast ; 31: 181-185, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27871025

RESUMO

BACKGROUND: The aim of our study was to assess various predictors for local recurrence (LR) in patients undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: An audit was performed of 582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients undergoing BCS, local guidelines reported a margin of ≥10 mm during the above period. Guideline with regard to margin of excision changes soon after this period. We retrospectively analysed clinical and pathological risk factors for local recurrence in patients undergoing BCS. Statistical analysis was carried out using SPSS version 19, and a cox regression model for multivariate analysis of local recurrence was used. RESULTS: Overall 239 women had BCS for DCIS during the above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate was 17% (40/239. LR was more common in patients ≤50 years: (10/31 patients, 32%) compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of patients (6/14) with <5 mm margin developed LR which was significantly higher compared to patients with 5-9 mm margin (12%, 3/25) and with ≥10 mm margin (14%, 27/188, P = 0.01). On multivariate analysis age ≤50 years, <5 mm pathological margin were independent prognostic factors for local recurrence. CONCLUSION: Our study shows that younger age (≤50 years) and a margin < 5 mm are poor prognostic factors for LR in patients undergoing breast conservation surgery for DCIS.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Fatores de Risco
4.
Breast ; 23(5): 567-72, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24874285

RESUMO

BACKGROUND: This pilot study aimed to test the possibility of therapeutic benefit imparted by early intervention based on sequential tumour marker (TM) measurements during follow-up of primary breast cancer (PBC) patients. METHODS: Patients with oestrogen receptor positive PBC with no clinical and/or radiological evidence of metastases were recruited and followed-up 3-monthly with clinical assessment and TM (CA15.3 and CEA) measurements. The clinical team was blinded to the TM results. Asymptomatic patients who developed raised TMs (based on pre-defined cut-offs) were randomised to either 'treatment change' (either start or change of adjuvant endocrine agent to another agent) or 'no change' (control). Patients who developed symptomatic metastases came off the study. The primary and secondary endpoints were intervals from randomisation to symptomatic metastases and to last follow-up/death respectively. RESULTS: Eighty-five patients (median age = 54 years (30-72)) were recruited with a median follow-up of 81 months (1-124). Sixteen patients were randomised as described. There was no significant difference (treatment change versus no change) with regards to interval from randomisation to symptomatic metastases - 23 (2-62) and 22 (1-63) months respectively (p = 0.9), as well as interval from randomisation to last follow-up/death - 36 (7-63) and 37 (10-63) months respectively (p = 0.9). CONCLUSIONS: Despite long follow-up (up to 10+ years), this small study has thus far shown no significant difference in outcome. However, we have confirmed the feasibility of this study design but a larger study will be required to show if there is a benefit to this approach.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Antígeno Carcinoembrionário/sangue , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Mucina-1/sangue , Adulto , Idoso , Anastrozol , Neoplasias Ósseas/sangue , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Detecção Precoce de Câncer/métodos , Feminino , Seguimentos , Gosserrelina/administração & dosagem , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Projetos Piloto , Método Simples-Cego , Tamoxifeno/administração & dosagem , Resultado do Tratamento , Triazóis/administração & dosagem
5.
Ann Oncol ; 24(10): 2543-2548, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23788750

RESUMO

BACKGROUND: The progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies. PATIENTS AND METHODS: This randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer. RESULTS: Patients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥ 35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥ 6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥ 6 months. Overall, 61 of 68 patients (90%) had ≥ 1 adverse event (AE), the most frequent (≥ 10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs. CONCLUSION: Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estrenos/uso terapêutico , Receptores de Progesterona/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Estrenos/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismo , Resultado do Tratamento
6.
Ann Oncol ; 23(6): 1378-86, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22317766

RESUMO

BACKGROUND: Hormone receptor-positive advanced breast cancer is an increasing health burden. Although endocrine therapies are recognised as the most beneficial treatments for patients with hormone receptor-positive advanced breast cancer, the optimal sequence of these agents is currently undetermined. METHODS: We reviewed the available data on randomised controlled trials (RCTs) of endocrine therapies in this treatment setting with particular focus on RCTs reported over the last 15 years that were designed based on power calculations on primary end points. RESULTS: In this paper, data are reviewed in postmenopausal patients for the use of tamoxifen, aromatase inhibitors and fulvestrant. We also consider the available data on endocrine crossover studies and endocrine therapy in combination with chemotherapy or growth factor therapies. Treatment options for premenopausal patients and those with estrogen receptor-/human epidermal growth factor receptor 2-positive tumours are also evaluated. CONCLUSION: We present the level of evidence available for each endocrine agent based on its efficacy in advanced breast cancer and a diagram of possible treatment pathways.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo
7.
Ann Oncol ; 23(9): 2296-2300, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22357257

RESUMO

BACKGROUND: Long-term analysis of a randomised trial in Nottingham comparing tamoxifen versus surgery as initial treatment demonstrated that in oestrogen receptor (ER)-unselected cases, surgery achieved better local control, with no difference in overall survival. It was suggested that for patients with ER-rich tumours, local control and survival may be comparable. We now present long-term follow-up of a randomised trial designed to address this clinical scenario. PATIENTS AND METHODS: One hundred and fifty three fit elderly (≥70 years) women with clinically node-negative primary invasive breast carcinoma <5 cm of high ER content [histochemical (H) score ≥100] were randomised 2:1 to primary tamoxifen (Tam) (N = 100) or mastectomy with adjuvant tamoxifen (Mx + Tam) (N = 53). RESULTS: With median follow-up of 78 months, there was no statistically significant difference in 10-year rates of regional recurrence (9.0% versus 7.5%), metastasis (8.0% versus 13.2%), breast cancer-specific survival (89.0% versus 86.8%) or overall survival (64.0% versus 66.0%) between Tam and Mx + Tam; however, local control was inferior with Tam (local failure rates 43.0% versus 1.9%; P < 0.001). CONCLUSION: Irrespective of the degree of ER positivity, surgery achieved better local control. However, there was excellent and similar survival in both groups. Tam could be considered in those who are 'frail', refuse or prefer not to initially undergo surgery.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma/terapia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Mastectomia , Invasividade Neoplásica , Neoplasias Hormônio-Dependentes/mortalidade , Estatísticas não Paramétricas , Resultado do Tratamento
8.
Crit Rev Oncol Hematol ; 78(3): 260-4, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20447833

RESUMO

A recent Cochrane review of trials involving elderly women with operable primary breast cancer showed no significant difference in overall survival between surgery (±adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We report the final results of a randomised pilot trial comparing primary tamoxifen and wedge mastectomy as initial treatment in this population. One hundred and thirty-one women >70 years with early operable primary breast cancer (<5 cm), unselected for oestrogen receptor (ER), entered the trial in 1982-1987. Sixty-eight patients were allocated to tamoxifen only and 67 to wedge mastectomy only, as primary treatment. At 20 years of follow-up, the median time to local failure was significantly shorter in the tamoxifen arm though approximately one-fifth of patients in this group did not develop local failure requiring mastectomy. There was no difference in regional recurrence, distant metastases or overall survival between the mastectomy and tamoxifen arms. In this small study, primary endocrine therapy achieved local control in 30% of those surviving at 5 years and 20% at 10 years, unselected for ER. The primary therapy used did not significantly affect regional recurrence, incidence of distant metastases or overall survival. Primary endocrine therapy should certainly be considered in those patients with ER positive tumours and who are unfit (based on life expectancy) for or refuse surgery.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Mastectomia , Tamoxifeno/uso terapêutico , Idoso , Feminino , Seguimentos , Humanos , Projetos Piloto , Análise de Sobrevida
9.
Ann Oncol ; 22(2): 383-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20675559

RESUMO

BACKGROUND: Autoantibodies may be present in a variety of underlying cancers several years before tumours can be detected and testing for their presence may allow earlier diagnosis. We report the clinical validation of an autoantibody panel in newly diagnosed patients with lung cancer (LC). PATIENTS AND METHODS: Three cohorts of patients with newly diagnosed LC were identified: group 1 (n = 145), group 2 (n = 241) and group 3 (n = 269). Patients were individually matched by gender, age and smoking history to a control individual with no history of malignant disease. Serum samples were obtained after diagnosis but before any anticancer treatment. Autoantibody levels were measured against a panel of six tumour-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2). Assay sensitivity was tested in relation to demographic variables and cancer type/stage. RESULTS: The autoantibody panel demonstrated a sensitivity/specificity of 36%/91%, 39%/89% and 37%/90% in groups 1, 2 and 3, respectively, with good reproducibility. There was no significant difference between different LC stages, indicating that the antigens included covered the different types of LC well. CONCLUSION: This assay confirms the value of an autoantibody panel as a diagnostic tool and offers a potential system for monitoring patients at high risk of LC.


Assuntos
Autoanticorpos/sangue , Neoplasias Pulmonares/diagnóstico , Estudos de Coortes , Humanos , Neoplasias Pulmonares/imunologia
10.
Eur J Cancer ; 46(16): 2936-42, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20832294

RESUMO

Trials have shown superiority of aromatase inhibitors (AIs) over tamoxifen for post-menopausal oestrogen receptor-positive advanced breast cancer (ER+ABC). We previously reported the use of goserelin plus anastrozole (G+A) as second-line endocrine therapy for pre-menopausal ER+ABC. We report clinical and endocrine data from G+A as first-line systemic therapy. Thirty-six patients (median age=44 years) with metastatic (N=28) and locally advanced disease were administered G+A for ≥6 months (unless progressed prior). Some (N=13) received further therapy with goserelin plus another AI (steroidal), exemestane (G+E). Serial serum hormone assays (oestradiol, dehydroepiandrosterone sulphate, testosterone, follicle stimulating hormone and luteinising hormone) were performed. Twenty-four patients (67%) derived clinical benefit (CB) (5% complete response, 31% partial response, 31% stable disease for ≥6 months) with median time to progression and duration of CB of 12 (2-47) and 24+(7-78+) months respectively. Ten patients were still receiving first-line G+A at analysis. Amongst 13 patients who went onto receive G+E, 38% achieved CB with a mean duration of 13+(7-32) months. Therapy was well tolerated with no withdrawals. The combination of G+A resulted in 98% reduction (from pre-treatment to 6-month) in median levels of oestradiol (from 574.5 pmol/L; inter-quartile range (IQR)=209-1426; (N=6) to 13.45 pmol/L; IOQ=5.5-31.5 (N=4) whilst the levels of other hormones had minimal fluctuations during therapy. The combinations of ovarian function suppression (using G) and AIs produce sustained CB and minimal side effects in pre-menopausal ER+ABC with significant reduction in oestradiol levels. Within the limitations of being a non-randomised study, they should be considered in appropriate patients with hormone-sensitive ABC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ovário/efeitos dos fármacos , Adulto , Anastrozol , Androstadienos/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Feminino , Hormônio Liberador de Gonadotropina , Gosserrelina/administração & dosagem , Hormônios/metabolismo , Humanos , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Pré-Menopausa , Tamoxifeno/administração & dosagem , Triazóis/administração & dosagem
11.
Ann Oncol ; 21(8): 1687-1693, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20124350

RESUMO

BACKGROUND: Publications on autoantibodies to tumour-associated antigens (TAAs) have failed to show either calibration or reproducibility data. The validation of a panel of six TAAs to which autoantibodies have been described is reported here. MATERIALS AND METHODS: Three separate groups of patients with newly diagnosed lung cancer were identified, along with control individuals, and their samples used to validate an enzyme-linked immunosorbant assay. Precision, linearity, assay reproducibility and antigen batch reproducibility were all assessed. RESULTS: For between-replicate error, samples with higher signals gave coefficients of variation (CVs) in the range 7%-15%. CVs for between-plate variation were only 1%-2% higher. For between-run error, CVs were in the range 15%-28%. In linearity studies, the slope was close to 1.0 and correlation coefficient values were generally >0.8. The sensitivity and specificity of individual batches of antigen varied slightly between groups of patients; however, the sensitivity and specificity of the panel of antigens as a whole remained constant. The validity of the calibration system was demonstrated. CONCLUSIONS: A calibrated six-panel assay of TAAs has been validated for identifying nearly 40% of primary lung cancers via a peripheral blood test. Levels of reproducibility, precision and linearity would be acceptable for an assay used in a regulated clinical setting.


Assuntos
Autoanticorpos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Neoplasias Pulmonares/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Controle de Qualidade , Reprodutibilidade dos Testes
12.
Ann Oncol ; 21(6): 1246-1253, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19875750

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression increases the aggressiveness of breast cancer cells resulting in poorer prognosis. Patients with HER2-positive disease are less responsive to endocrine therapies. Trastuzumab monotherapy results in objective responses in only approximately 15% of patients. Fulvestrant retains activity in cells overexpressing HER2 that are resistant to other endocrine treatments. This retrospective study evaluated response to fulvestrant treatment among HER2-positive patients with advanced breast cancer (ABC). PATIENTS AND METHODS: Clinical experience data from 10 treatment centres were pooled. Postmenopausal patients with predominantly hormone receptor-positive and HER2-positive disease were included. Clinical benefit (CB) was defined as the proportion of patients achieving a response to treatment (partial or complete) or stable disease lasting >/=6 months. RESULTS: Data for 102 patients were analysed. Fulvestrant resulted in an overall CB rate of 42% (43/101) in HER2-positive patients and 40% (25/63) in patients with visceral disease. Median duration of treatment was 14.5 months (range 6-44 months). Fulvestrant showed activity up to the fourth line of endocrine therapy and up to the seventh line of overall therapy. CONCLUSIONS: Results indicate that fulvestrant may be a suitable treatment option in extensively pre-treated patients with HER2-positive, hormone receptor-positive ABC. Further exploration of its use in this patient population is warranted.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Estradiol/análogos & derivados , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Quimioterapia Adjuvante , Progressão da Doença , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estradiol/farmacologia , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento , Regulação para Cima
13.
Breast ; 18(6): 339-44, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19836953

RESUMO

Chemotherapeutic agents have dominated neoadjuvant treatment compared to endocrine agents in the past and have demonstrated their ability to produce tumour shrinkage to allow breast conservation. However, in the more recent setting, studies have been emerging with the use of aromatase inhibitors, especially comparing its use with tamoxifen in selected group of patients. The role of tamoxifen in its ability to achieve tumour shrinkage has been evaluated in the past, and has shown to produce slow but sustained response. Aromatase inhibitors have shown superiority over tamoxifen in adjuvant and metastatic setting, and the aim of our study was to compare their outcome with regard to response and breast conservation in the neoadjuvant setting. We also looked into optimum duration of neoadjuvant treatment and also the role of pathological complete response as a surrogate marker for clinical outcome. Our review highlights the superiority of aromatase inhibitors over tamoxifen in the neoadjuvant setting and even challenges chemotherapy with regard to response in selected group of patients.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Mastectomia Segmentar , Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Breast ; 18(3): 204-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19464177

RESUMO

BACKGROUND: Tamoxifen has a protective effect on bone metabolism in breast cancer; aromatase inhibitors deleterious and that of fulvestrant is unknown. METHODS: Fourteen locally advanced breast cancers with clinical benefit on fulvestrant (250 mg/month) as first-line primary endocrine therapy had sequential serum bone-specific alkaline phosphatase (BAP), N-terminal propeptide of procollagen type 1 (PINP) and C-terminal telopeptide (CTX) at 0, 1, 6, 12, and 18 months. Mean percentage changes (95% CI) were calculated. RESULTS: Changes from baseline at 1, 6, 12, and 18 months with BAP (3.9-46.8 ng/ml) were +1.5 (-9.8 to +12.9), +2.2 (-22.1 to +26.6), +17.6 (-12.4 to +47.6), +10.8 (-29.9 to +51.7); with PINP (20.6-82.1 ng/ml) were +3.4 (-12.0 to 19.0), +18.8 (-36.7 to +74.2), +47.5 (-21.4 to 116.3), +33.3 (-49.5 to +116.1) and with CTX (0.14-1.35 ng/ml) were +30.8 (0.1 to +61.6), +13.9 (-22.3 to +50.2), +42.9 (-12.7 to +98.5), +45.2 (-28.3 to +118.8). CONCLUSIONS: Long-term (18 months) stability of bone markers may be exploited by using fulvestrant earlier in sequence of endocrine therapies particularly in adjuvant setting in those with pre-existing decreased bone mass.


Assuntos
Antineoplásicos/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Estradiol/análogos & derivados , Pós-Menopausa/sangue , Idoso , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Colágeno Tipo I/sangue , Estradiol/administração & dosagem , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Peptídeos/sangue , Projetos Piloto , Resultado do Tratamento
15.
J Pathol ; 217(1): 32-41, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18825690

RESUMO

The AP-2gamma transcription factor encoded by the TFAP2C gene is a member of a family of homologous DNA binding proteins that play essential roles during vertebrate embryogenesis but show a restricted pattern of expression in the adult. Elevated expression of the AP-2alpha and AP-2gamma family members has been associated with a number of neoplasms, particularly breast cancer. Here we present an exploratory immunohistochemical study of an archival primary breast tumour series (n = 75) with parallel clinicopathological data using a new, well-characterized antibody to AP-2gamma. Heterogeneous, exclusively nuclear expression of AP-2gamma was found in the epithelial and myoepithelial compartments of normal breast and within tumour epithelial cells. In the breast cancer series, the most notable association was a correlation between elevated levels of AP-2gamma and shortened patient survival (p = 0.0009*). This relationship was also conserved in ER-positive and ErbB2-negative patients; sub-groups generally considered to have a relatively good prognosis. When patient data for survival and duration of treatment response on anti-hormone therapy were examined by multivariate analysis, AP-2gamma was revealed in this study to be an independent predictor of outcome for both survival (p = 0.005) and response to anti-hormone therapy (p = 0.046). Studies using in vitro models confirmed that while tamoxifen response is associated with lower levels of AP-2gamma, acquisition of resistance to this and other anti-hormone measures (eg faslodex or oestrogen deprivation) is associated with high levels of nuclear AP-2gamma. Together these data suggest that elevated tumour AP-2gamma expression can contribute to the failure of cells to growth arrest following anti-hormone treatment and lead to sustained growth and poorer patient outcome.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Fator de Transcrição AP-2/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Prognóstico , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Fator de Transcrição AP-2/imunologia , Resultado do Tratamento , Células Tumorais Cultivadas
16.
Breast Cancer Res Treat ; 113(2): 403-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18311583

RESUMO

INTRODUCTION: There are trials comparing different neoadjuvant chemotherapy regimens for locally advanced primary breast cancer (LAPC). Few studies have evaluated alternative therapeutic approaches towards LAPC. A previous trial from our institute in LAPC patients unselected for oestrogen receptor (ER) status, comparing primary endocrine therapy versus multimodal treatment, showed no difference in breast cancer related deaths or overall survival. We report our experience of primary endocrine therapy in ER+ LAPC. METHODS: Between 1988 and 2007, 195 ER+, non-inflammatory LAPC patients were treated with primary endocrine agents in our institute, due to patient choice, being unfit for chemotherapy, or recruitment into the above mentioned trial. All patients had disease assessable by UICC criteria. RESULTS: Median age was 69 years. The median follow-up was 61 months. 154 patients (79%) received endocrine treatment alone. 185 patients (95%) derived clinical benefit (complete response/ partial response/ stable disease) for > or =6 months from primary endocrine therapy. Overall 5-year survival was 76% and 5-year breast cancer specific survival was 86%. CONCLUSION: In selected group of ER+ LAPC patients, primary endocrine treatment achieves excellent survival outcome and is a viable alternative to other modalities of treatment.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Terapia Combinada , Inglaterra/epidemiologia , Moduladores de Receptor Estrogênico/administração & dosagem , Feminino , Gosserrelina/administração & dosagem , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Receptores de Estrogênio/análise , Estudos Retrospectivos , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Resultado do Tratamento
17.
Eur J Surg Oncol ; 35(2): 113-22, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18502088

RESUMO

BACKGROUND: Most patients with locally advanced primary breast cancer have micrometastases at the time of presentation. Randomised trials on the use of neoadjuvant chemotherapy have not been carried out specifically in a population of breast cancer patients with locally advanced disease (LAPC). Despite this, its use for cytoreduction in these patients is an established option which may facilitate excision of the primary tumour and local lymph node metastasis for local control. Significant improvements in local disease control have been seen with recent advances in systemic chemotherapy regimens although thus far this has not shown in randomised trials to translate into overall survival benefits. METHODS: In this review, all studies where a large proportion (approximately 70%) of included patients with LAPC, were selected. A search of Medline and PubMed databases was performed. Specifically, the different chemotherapy regimens and their relation to oncological outcomes was assessed. RESULTS AND CONCLUSION: The studies assessed were heterogeneous with regard to patient selection and chemotherapy regimens used. A complete pathological response is the strongest predictor of disease-free and overall survival. Recent studies on the use of targeted biological therapies in addition to chemotherapy suggest that rates of complete pathological response may be significantly increased when compared to chemotherapy alone. Furthermore, improvements in localisation and imaging techniques, used in conjunction with the increasing use of oncoplastic breast-conserving techniques, highlight the possibility that a subgroup of these patients may safely be treated with breast conservation.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Saúde Global , Humanos , Mastectomia/métodos , Terapia Neoadjuvante/métodos , Taxa de Sobrevida , Resultado do Tratamento
18.
Breast ; 17(2): 195-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18164619

RESUMO

BACKGROUND: Axillary node sampling (ANS) is widely used in conjunction with breast conserving surgery in the treatment of primary breast cancers in the UK. Some evidence suggests that axillary staging techniques can miss intramammary nodes contained within the axillary tail of the breast. This study aims to assess the incidence of such nodes in completion mastectomy specimens in women who have had previous breast conserving surgery and ANS. METHODS: One hundred and fifty-seven completion mastectomy specimens were obtained from women who had previous breast conserving surgery and ANS, at the Nottingham Breast Institute over a 3-year period. The pathology samples underwent detailed histological examination to identify lymph nodes, and determine their disease status. RESULTS: Seventy-six (48%) of completion mastectomy specimens contained intramammary lymph nodes. Fifteen patients were upstaged (lymph node stage) because of the histological findings at completion mastectomy. One patient from the study population received additional systemic treatment, as a result of the upstaging. CONCLUSION: The incidence of intramammary nodes in this series correlates with previous data. This study shows that in breast cancer patients who undergo ANS, intramammary nodes, if present and more so positive, are unlikely to change systemic treatment decisions, but may increase the number of patients needing radiotherapy and or further axillary dissection.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Mastectomia , Axila , Mama , Feminino , Humanos , Incidência , Metástase Linfática , Mastectomia Segmentar , Estadiamento de Neoplasias
19.
Thorax ; 63(3): 228-33, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17932110

RESUMO

BACKGROUND: People with lung cancer usually present at a late stage in the course of their disease when their chances of long-term survival are low. At present there is little to offer for early diagnosis, even in those at high risk of developing the disease. Autoantibodies have been shown to be present in the circulation of people with various forms of solid tumour before cancer-associated antigens can be detected, and these molecules can be measured up to 5 years before symptomatic disease. OBJECTIVE: To assess the potential of a panel of tumour-associated autoantibody profiles as an aid to other lung cancer screening modalities. METHODS: Plasma from normal controls (n = 50), patients with non-small cell lung cancer (n = 82) and patients with small cell lung cancer (n = 22) were investigated for the presence of autoantibodies to p53, c-myc, HER2, NY-ESO-1, CAGE, MUC1 and GBU4-5 by enzyme-linked immunosorbent assay. RESULTS: Raised levels of autoantibodies were seen to at least 1/7 antigens in 76% of all the patients with lung cancer plasma tested, and 89% of node-negative patients, with a specificity of 92%. There was no significant difference between the detection rates in the lung cancer subgroups, although more patients with squamous cell carcinomas (92%) could be identified. CONCLUSION: Measurement of an autoantibody response to one or more tumour-associated antigens in an optimised panel assay may provide a sensitive and specific blood test to aid the early detection of lung cancer.


Assuntos
Anticorpos Antineoplásicos/sangue , Autoanticorpos/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Formação de Anticorpos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma de Células Pequenas/imunologia , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Humanos , Neoplasias Pulmonares/imunologia , Pessoa de Meia-Idade
20.
Breast ; 17(1): 98-103, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17890090

RESUMO

BACKGROUND: The aim of this study was to determine whether bone scans (BS) can be avoided if pelvis was included in CT thorax and abdomen to detect bony metastases from breast cancer. MATERIALS AND METHODS: Results of 77 pairs of CT (thorax, abdomen, and pelvis) and BS in newly diagnosed patients with metastatic breast cancer (MBC) were compared prospectively for 12 months. Both scans were blindly assessed by experienced radiologists and discussed at multidisciplinary team meetings regarding the diagnosis of bone metastases. RESULTS: CT detected metastatic bone lesions in 43 (98%) of 44 patients with bone metastases. The remaining patient had a solitary, asymptomatic bony metastasis in shaft of femur. BS was positive in all patients with bone metastases. There were 11 cases of false positive findings on BS. CONCLUSION: Our findings suggest routine BS of patients presenting with MBC is not required if CT (thorax, abdomen, and pelvis) is performed.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Radiografia Abdominal/métodos , Radiografia Torácica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pelve/diagnóstico por imagem , Estudos Prospectivos , Cintilografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
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