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1.
Eur J Surg Oncol ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33349523

RESUMO

BACKGROUND: The aim was to evaluate the cost-utility of four common surgical treatment pathways for breast cancer: mastectomy, breast-conserving therapy (BCT), implant breast reconstruction (BR) and autologous-BR. METHODS: Patient-level healthcare consumption data and results of a large quality of life (QoL) study from five Dutch hospitals were combined. The cost-effectiveness was assessed in terms of incremental costs and quality adjusted life years (QALYs) over a 10-year follow-up period. Costs were assessed from a healthcare provider perspective. RESULTS: BCT resulted in comparable QoL with lower costs compared to implant-BR and autologous-BR and showed better QoL with higher costs than mastectomy (€17,246/QALY). QoL outcomes and costs of especially autologous-BR were affected by the relatively high occurrence of complications. If reconstruction following mastectomy was performed, implant-BR was more cost-effective than autologous-BR. CONCLUSION: The occurrence of complications had a substantial effect on costs and QoL outcomes of different surgical pathways for breast cancer. When this was taken into account, BCT was most the cost-effective treatment. Even with higher costs and a higher risk of complications, implant-BR and autologous-BR remained cost-effective over mastectomy. This pleas for adapting surgical pathways to individual patient preferences in the trade-off between the risks of complications and expected outcomes.

2.
Value Health ; 23(9): 1191-1199, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32940237

RESUMO

OBJECTIVES: Hospital comparisons to improve quality of care require valid and reliable quality indicators. We aimed to test the validity and reliability of 6 breast cancer indicators by quantifying the influence of case-mix and random variation. METHODS: The nationwide population-based database included 79 690 patients with breast cancer from 91 Dutch hospitals between 2011 and 2016. The indicator-scores calculated were: (1) irradical breast-conserving surgery (BCS) for invasive disease, (2) irradical BCS for ductal carcinoma-in-situ, (3) breast contour-preserving treatment, (4) magnetic resonance imaging (MRI) before neo-adjuvant chemotherapy, (5) radiotherapy for locally advanced disease, and (6) surgery within 5 weeks from diagnosis. Case-mix and random variation adjustments were performed by multivariable fixed and random effect logistic regression models. Rankability quantified the between-hospital variation, representing unexplained differences that might be the result of the level of quality of care, as low (<50%), moderate (50%-75%), or high (>75%). RESULTS: All of the indicators showed between-hospital variation with wide (interquartile) ranges. Case-mix adjustment reduced variation in indicators 1 and 3 to 5. Random variation adjustment (further) reduced the variation for all indicators. Case-mix and random variation adjustments influenced the indicator-scores of individual hospitals and their ranking. Rankability was poor for indicator 1, 2, and 5, and moderate for 3, 4, and 6. CONCLUSIONS: The 6 indicators lacked validity and/or reliability to a certain extent. Although measuring quality indicators may stimulate quality improvement in general, comparisons and judgments of individual hospital performance should be made with caution if based on indicators that have not been tested or adjusted for validity and reliability, especially in benchmarking.


Assuntos
Neoplasias da Mama/terapia , Hospitais/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Benchmarking , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Melhoria de Qualidade , Reprodutibilidade dos Testes
3.
Value Health ; 23(9): 1200-1209, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32940238

RESUMO

OBJECTIVES: To improve quality in breast cancer care, large numbers of quality indicators are collected per hospital, but benchmarking remains complex. We aimed to assess the validity of indicators, develop a textbook outcome summary measure, and compare case-mix adjusted hospital performance. METHODS: From a nationwide population-based registry, all 79 690 nonmetastatic breast cancer patients surgically treated between 2011 and 2016 in 91 hospitals in The Netherlands were included. Twenty-one indicators were calculated and their construct validity tested by Spearman's rho. Between-hospital variation was expressed by interquartile range (IQR), and all valid indicators were included in the summary measure. Standardized scores (observed/expected based on case mix) were calculated as above (>100) or below (<100) expected. The textbook outcome was presented as a continuous and all-or-none score. RESULTS: The size of between-hospital variation varied between indicators. Sixteen (76%) of 21 quality indicators showed construct validity, and 13 were included in the summary measure after excluding redundant indicators that showed collinearity with others owing to strong construct validity. The median all-or-none textbook outcome score was 49% (IQR 42%-54%) before and 49% (IQR 48%-51%) after case-mix adjustment. From the total of 91 hospitals, 3 hospitals were positive (3%) and 9 (10%) were negative outliers. CONCLUSIONS: The textbook outcome summary measure showed discriminative ability when hospital performance was presented as an all-or-none score. Although indicator scores and outlier hospitals should always be interpreted cautiously, the summary measure presented here has the potential to improve Dutch breast cancer quality indicator efforts and could be implemented to further test its validity, feasibility, and usefulness.


Assuntos
Neoplasias da Mama/terapia , Indicadores de Qualidade em Assistência à Saúde/normas , Benchmarking , Neoplasias da Mama/epidemiologia , Hospitais/normas , Humanos , Países Baixos/epidemiologia , Qualidade da Assistência à Saúde , Medição de Risco
4.
Ann Surg Oncol ; 27(13): 5296-5302, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32578065

RESUMO

BACKGROUND: There are currently two widely used methods for preoperative localization of ductal carcinoma in situ (DCIS) of the breast: wire-guided localization (WGL) and radioactive seed localization (RSL). Several studies compared these localization techniques in small cohorts. OBJECTIVE: The aim of this study was to compare the surgical resection margin status between RSL and WGL in a large national cohort of patients with DCIS. PATIENTS AND METHODS: We included patients from the Dutch Pathology Registry who underwent breast-conserving surgery for DCIS by either RSL (n = 1851) or WGL (n = 2187) between 2009 and 2019. Several clinicopathological characteristics were compared between these two groups, including resection margin status and number of re-excisions. RESULTS: Patients undergoing RSL were younger (p = 0.014) and were more often diagnosed with a large DCIS (p = 0.013), high grade DCIS (p < 0.001) and comedonecrosis (p < 0.001) compared with patients undergoing WGL. There was no significant difference in resection margin status between both groups (p = 0.089) and the number of re-excisions (p = 0.429). However, in case of re-excision, patients in the RSL group were more often treated with breast-conserving surgery (p = 0.029). CONCLUSION: In this large national cohort study of patients with DCIS, we demonstrated that there was no difference in resection margin status between both procedures, or in the number of re-excisions, but patients in the RSL group were more often treated with breast-conserving therapy in case of a re-excision.

5.
Breast Cancer Res Treat ; 181(2): 423-434, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279280

RESUMO

BACKGROUND: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). METHODS: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope. RESULTS: The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula. CONCLUSIONS: Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.


Assuntos
Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Segunda Neoplasia Primária/patologia , Medição de Risco/métodos , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Agências Internacionais , Mastectomia , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/cirurgia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Fatores de Risco
6.
Breast J ; 26(6): 1213-1215, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32160651

RESUMO

As high breast cancer survival rates are achieved nowadays, irrespective of type of surgery performed, prediction of long-term physical, sexual, and psychosocial outcomes is very important in treatment decision-making. Patient-reported outcomes (PROs) can help facilitate this shared decision-making. Given the significance of more personalized medicine and the growing trend on the application of machine learning techniques, we are striving to develop an algorithm using machine learning techniques to predict PROs in breast cancer patients treated with breast surgery. This short communication describes the bottlenecks in our attempt to predict PROs.

7.
Cancer Causes Control ; 31(5): 403-416, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32130573

RESUMO

PURPOSE: The risk of being diagnosed with contralateral breast cancer (CBC) is an important health issue among breast cancer survivors. There is an increasing interest in the effect of lifestyle and reproductive factors on CBC risk, since these factors may partly be modifiable. We performed a systematic review and meta-analysis and aimed to evaluate the impact of lifestyle and reproductive factors on CBC risk in population-based breast cancer studies. METHODS: The PubMed electronic database was searched up to 2nd November 2019, for relevant publications. Of the included studies, a meta-analysis per lifestyle or reproductive factor was performed. RESULTS: Thirteen out of 784 publications were used for the meta-analysis. Body mass index (≥ 25 vs. < 25 kg/m2; RR = 1.22; 95% CI 1.01-1.47) was associated with increased CBC risk. The estimates for alcohol use (ever vs. never; RR = 1.15; 95% CI 1.02-1.31) and age at primiparity (≥ 25 vs. < 25 years; RR = 1.06; 95% CI 1.02-1.10) also showed an association with increased CBC risk. For parity (≥ 4 vs. nulliparous; RR = 0.56; 95% CI 0.42-0.76) and age at menopause (< 45 vs ≥ 45 years; RR = 0.79; 95% CI 0.67-0.93), results from two studies suggested a decreased CBC risk. We observed no association between CBC and smoking, age at menarche, oral contraceptive use, gravidity, breastfeeding, or menopausal status. Overall, the number of studies per risk factor was limited (n = 2-5). CONCLUSIONS: BMI is a modifiable risk factor for CBC. Data on the effect of other modifiable lifestyle and reproductive factors are limited. For better counseling of patients on lifestyle effects, more studies are urgently needed.


Assuntos
Neoplasias da Mama/etiologia , Estilo de Vida , Segunda Neoplasia Primária/etiologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Paridade , Gravidez , História Reprodutiva , Fatores de Risco , Adulto Jovem
9.
Breast Cancer Res ; 22(1): 8, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948486

RESUMO

BACKGROUND: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. METHODS: A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. RESULTS: There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. CONCLUSION: We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/epidemiologia , Mutação , Salpingo-Ooforectomia/métodos , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Humanos , Incidência , Agências Internacionais , Menopausa , Pessoa de Meia-Idade , Estudos Prospectivos , Comportamento de Redução do Risco
10.
Int J Cancer ; 146(5): 1189-1197, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31018242

RESUMO

Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen-detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast-conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So-called "recurrences" are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/patologia , Recidiva Local de Neoplasia/epidemiologia , Conduta Expectante/métodos , Biópsia , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Progressão da Doença , Feminino , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia/patologia , Prevalência , Projetos de Pesquisa , Estudos Retrospectivos , Medição de Risco/métodos
11.
Value Health ; 22(10): 1197-1226, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31563263

RESUMO

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly being used to improve care delivery and are becoming part of routine clinical practice. OBJECTIVE: This systematic review aims to give an overview of PROM administration methods and their facilitators and barriers in breast cancer clinical practice. METHODS: A systematic literature search was conducted in Embase, MEDLINE, PsycINFO, Cochrane Central, CINAHL, and Web of Science for potentially relevant articles from study inception to November 2017. Reference lists of screened reviews were also checked. After inclusion of relevant articles, data were extracted and appraised by 2 investigators. RESULTS: A total of 2311 articles were screened, of which 34 eligible articles were ultimately included. Method and frequency of PROM collection varied between studies. The majority of studies described a promising effect of PROM collection on patients (adherence, symptom distress, quality of life, acceptability, and satisfaction), providers (willingness to comply, clinical decision making, symptom management), and care process or system outcomes (referrals, patient-provider communication, hospital visits). A limited number of facilitators and barriers were identified, primarily of a technical and behavioral nature. CONCLUSION: Although interpreting the impact of PROM collection in breast cancer care is challenging owing to considerations of synergistic (multicomponent) interventions and generalizability issues, this review found that systematic PROM collection has a promising impact on patients, providers, and care processes/ systems. Further standardization and reporting on method and frequency of PROM collection might help increase the effectiveness of PROM interventions and is warranted to enhance their overall impact.


Assuntos
Neoplasias da Mama , Assistência ao Paciente , Medidas de Resultados Relatados pelo Paciente , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Assistência ao Paciente/normas , Melhoria de Qualidade , Autorrelato
12.
Breast Cancer Res Treat ; 177(3): 723-733, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302855

RESUMO

BACKGROUND: In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit of BRRM over BC surveillance has been reported yet. METHODS: In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specific mortality rates, separately for BRCA1 and BRCA2 mutation carriers. RESULTS: During a mean follow-up of 10.3 years, 722 out of 1712 BRCA1 (42%) and 406 out of 1145 BRCA2 (35%) mutation carriers underwent BRRM. For BRCA1 mutation carriers, we observed 52 deaths (20 from BC) in the surveillance group, and 10 deaths (one from BC) after BRRM. The hazard ratios were 0.40 (95% CI 0.20-0.90) for overall mortality and 0.06 (95% CI 0.01-0.46) for BC-specific mortality. BC-specific survival at age 65 was 93% for surveillance and 99.7% for BRRM. For BRCA2 mutation carriers, we observed 29 deaths (7 from BC) in the surveillance group, and 4 deaths (no BC) after BRRM. The hazard ratio for overall mortality was 0.45 (95% CI 0.15-1.36). BC-specific survival at age 65 was 98% for surveillance and 100% for BRRM. CONCLUSION: BRRM was associated with lower mortality than surveillance for BRCA1 mutation carriers, but for BRCA2 mutation carriers, BRRM may lead to similar BC-specific survival as surveillance. Our findings support a more individualized counseling based on BRCA mutation type.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/etiologia , Neoplasias da Mama/prevenção & controle , Heterozigoto , Mutação , Mastectomia Profilática , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Feminino , Mutação em Linhagem Germinativa , Humanos , Mortalidade , Países Baixos/epidemiologia , Prognóstico , Mastectomia Profilática/métodos , Vigilância em Saúde Pública , Comportamento de Redução do Risco
13.
Eur J Cancer Care (Engl) ; 28(3): e13092, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31074162

RESUMO

INTRODUCTION: Current follow-up arrangements for breast cancer do not optimally meet the needs of individual patients. We therefore reviewed the evidence on preferences and patient involvement in decisions about breast cancer follow-up to explore the potential for personalised care. METHODS: Studies published between 2008 and 2017 were extracted from MEDLINE, PsycINFO and EMBASE. We then identified decision categories related to content and form of follow-up. Criteria for preference sensitiveness and patient involvement were compiled and applied to determine the extent to which decisions were sensitive to patient preferences and patients were involved. RESULTS: Forty-one studies were included in the full-text analysis. Four decision categories were identified: "surveillance for recurrent/secondary breast cancer; consultations for physical and psychosocial effects; recurrence-risk reduction by anti-hormonal treatment; and improving quality of life after breast cancer." There was little evidence that physicians treated decisions about anti-hormonal treatment, menopausal symptoms, and follow-up consultations as sensitive to patient preferences. Decisions about breast reconstruction were considered as very sensitive to patient preferences, and patients were usually involved. CONCLUSION: Patients are currently not involved in all decisions that affect them during follow-up, indicating a need for improvements. Personalised follow-up care could improve resource allocation and the value of care for patients.


Assuntos
Assistência ao Convalescente/métodos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Preferência do Paciente , Qualidade de Vida , Sobreviventes de Câncer , Feminino , Humanos , Imagem por Ressonância Magnética , Mamoplastia , Mamografia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/prevenção & controle , Participação do Paciente , Medicina de Precisão
14.
Brachytherapy ; 18(2): 204-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30528494

RESUMO

PURPOSE: Accelerated partial breast irradiation is a treatment option for selected patients with early-stage breast cancer. Some accelerated partial breast irradiation techniques lead to skin toxicity with the skin dose as a main risk factor. Biodegradable spacers are effective and safe in prostate brachytherapy to protect the rectum. We hypothesize that a subcutaneous spacer injection reduces the skin dose in breast brachytherapy. METHODS AND MATERIALS: Ultrasound-guided spacer injections, either hyaluronic acid (HA) or iodined polyethylene glycol (PEG), were performed on fresh mastectomy specimens. Success was defined as a spacer thickness of ≥5 mm in the high-dose skin area. Usability was scored using the system usability scale. Pre and postinjection CT scans were used to generate low-dose-rate seed brachytherapy treatment plans after defining a clinical target volume. Maximum dose to small skin volumes (D0.2cc) and existence of hotspots (isodose ≥90% on 1 cm2 of skin) were calculated as skin toxicity indicators. RESULTS: We collected 22 mastectomy specimens; half had HA and half had PEG injection. Intervention success was 100% for HA and 90.9% for PEG (p = NS). Hydrodissection was feasible in 81.8% with HA and 63.6% with PEG. Median system usability scale score was 97.5 for HA and 82.5 for PEG (p < 0.001). Mean D0.2cc was 80.8 Gy without spacer and 53.7 Gy with spacer (p < 0.001). Skin hotspots were present in 40.9% without spacer but none with spacer (p < 0.001). CONCLUSIONS: A spacer injection in mastectomy specimens is feasible. An extra 5 mm space is always achieved, thereby potentially reducing the skin dose dramatically in low-dose-rate seed breast brachytherapy.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Ácido Hialurônico/administração & dosagem , Polietilenoglicóis/administração & dosagem , Substâncias Protetoras/administração & dosagem , Radiodermatite/prevenção & controle , Braquiterapia/efeitos adversos , Feminino , Humanos , Injeções , Mastectomia , Projetos Piloto , Doses de Radiação , Radiodermatite/etiologia , Pele/efeitos da radiação
15.
Ann Surg ; 269(3): 432-442, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30312200

RESUMO

OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis to assess the accuracy of different surgical axillary staging procedures compared with ALND. SUMMARY OF BACKGROUND DATA: Optimal axillary staging after neoadjuvant systemic therapy (NST) in node-positive breast cancer is an area of controversy. Several less invasive procedures, such as sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and targeted axillary dissection (a combination of SLNB and a MARI-like procedure), have been proposed to replace the conventional axillary lymph node dissection (ALND) with its concomitant morbidity. METHODS: PubMed and Embase were searched for studies comparing less invasive surgical axillary staging procedures to ALND to identify axillary burden after NST in patients with pathologically confirmed node-positive breast cancer (cN+). A meta-analysis was performed to compare identification rate (IFR), false-negative rate (FNR), and negative predictive value (NPV). RESULTS: Of 1132 records, 20 unique studies with 2217 patients were included in quantitative analysis: 17 studies on SLNB, 1 study on MARI, and 2 studies on a combination procedure. Overall axillary pathologic complete response rate was 37%. For SLNB, pooled rates of IFR and FNR were 89% and 17%. NPV ranged from 57% to 86%. For MARI, IFR was 97%, FNR 7%, and NPV 83%. For the combination procedure, IFR was 100%, FNR ranged from 2% to 4%, and NPV from 92% to 97%. CONCLUSION: Axillary staging by a combination procedure consisting of SLNB with excision of a pre-NST marked positive lymph node appears to be most accurate for axillary staging after NST. More evidence from prospective multicenter trials is needed to confirm this.


Assuntos
Neoplasias da Mama/patologia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Terapia Neoadjuvante , Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias
16.
Ann Surg ; 270(2): 364-372, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29727326

RESUMO

OBJECTIVE: To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers. SUMMARY OF BACKGROUND DATA: Although breast-conserving therapy (breast-conserving surgery followed by radiotherapy) has been associated with more local recurrences than mastectomy, no differences in overall survival have been found in randomized trials performed in the general breast cancer population. Whether breast-conservation can be safely offered to BRCA1/2 mutation carriers is debatable. METHODS: The study comprised a cohort of women with invasive breast cancer diagnosed <50 years and treated between 1970 and 2003 in 10 Dutch centers. Germline DNA for BRCA1/2 testing of most-prevalent mutations (covering ∼61%) was mainly derived from paraffin-blocks. Survival analyses were performed taking into account competing risks. RESULTS: In noncarriers (N = 5820), as well as in BRCA1 (N = 191) and BRCA2 (N = 70) mutation carriers, approximately half of the patients received breast-conserving therapy. Patients receiving mastectomy followed by radiotherapy had prognostically worse tumor characteristics and more often received systemic therapy. After adjustment for these potential confounders, patients who received breast-conserving therapy had a similar overall survival compared with patients who received mastectomy, both in noncarriers (hazard ratio [HR] = 0.95, confidence interval [CI] = 0.85-1.07, P = 0.41) and BRCA1 mutation carriers (HR = 0.80, CI = 0.42-1.51, P = 0.50). Numbers for BRCA2 were insufficient to draw conclusions. The rate of local recurrences after breast-conserving therapy did not differ between BRCA1 carriers (10-year risk = 7.3%) and noncarriers (10-year risk = 7.9%). CONCLUSION: Our results, together with the available literature, provide reassurance that breast-conserving therapy is a safe local treatment option to offer to BRCA1 mutation carriers with invasive breast cancer.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/cirurgia , DNA de Neoplasias/genética , Mastectomia Radical/métodos , Mastectomia Segmentar/métodos , Mutação , Adulto , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Taxa de Sobrevida/tendências
17.
Trials ; 19(1): 689, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558672

RESUMO

BACKGROUND: Accelerated partial breast irradiation (APBI) is a treatment option for selected early stage breast cancer patients. Some APBI techniques lead to skin toxicity with the skin dose as main risk factor. We hypothesize that a spacer injected between the skin and target volume reduces the skin dose and subsequent toxicity in permanent breast seed implant (PBSI) patients. METHODS: In this parallel-group, single-center, randomized controlled trial, the effect of a subcutaneous spacer injection on skin toxicity among patients treated with PBSI is tested. Eligibility for participation is derived from international guidelines for suitable patients for partial breast radiotherapy, e.g. women aged ≥ 50 years with a histologically proven non-lobular breast carcinoma and/or ductal carcinoma in situ (DCIS), tumor size ≤ 3 cm, node-negative, and PBSI technically feasible. Among exclusion criteria are neoadjuvant chemotherapy, lymphovascular invasion, and allergy for hyaluronic acid. For the patients allocated to receive spacer, after the PBSI procedure, 4-10 cc of biodegradable hyaluronic acid (Barrigel™, Palette Life Sciences, Santa Barbara, CA, USA or Restylane SubQ®, Galderma Benelux, Breda, the Netherlands) is injected directly under the skin using ultrasound guidance to create an extra 0.5-1 cm space between the treatment volume and the skin. The primary outcome is the rate of telangiectasia at two years, blindly assessed using Bentzen's 4-point scale. Secondary outcomes include: local recurrence; disease-free and overall survival rates; adverse events (pain, redness, skin/subcutaneous induration, radiation dermatitis, pigmentation, surgical site infection); skin dose; cosmetic and functional results; and health-related quality of life. A Fisher's exact test will be used to test differences between groups on the primary outcome. Previous studies found 22.4% telangiectasia at two years. We expect the use of a spacer could reduce the occurrence of telangiectasia to 7.7%. A sample size of 230 patients will allow for a 10% lost to follow-up rate. DISCUSSION: In this study, the effect of a subcutaneous spacer injection on the skin dose, late skin toxicity, and cosmetic outcome is tested in patients treated with PBSI in the setting of breast-conserving therapy. Our results will be relevant for most forms of breast brachytherapy as well as robotic radiosurgery, as skin spacers could protect the skin with these other techniques. TRIAL REGISTRATION: Netherlands Trial Register, NTR6549 . Registered on 27 June 2017.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Preenchedores Dérmicos/administração & dosagem , Ácido Hialurônico/análogos & derivados , Radiodermatite/prevenção & controle , Telangiectasia/prevenção & controle , Braquiterapia/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Preenchedores Dérmicos/efeitos adversos , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Injeções Subcutâneas , Mastectomia Segmentar , Pessoa de Meia-Idade , Países Baixos , Doses de Radiação , Radiodermatite/diagnóstico , Radiodermatite/etiologia , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Telangiectasia/diagnóstico , Telangiectasia/etiologia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
19.
Oncotarget ; 9(36): 24335-24346, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29849944

RESUMO

Background: MicroRNAs (miRs) are small RNA molecules, influencing messenger RNA (mRNA) expression and translation, and are readily detectable in blood. Some have been reported as potential breast cancer biomarkers. This study aimed to identify and validate miRs indicative of breast cancer. Results: Based on the discovery and literature, 18 potentially informative miRs were quantified in the validation cohort. Irrespective of patient and tumour characteristics, hsa-miR-652-5p was significantly upregulated in the malignant compared to benign patients (1.26 fold, P = 0.005) and therefore validated as potential biomarker. In the validation cohort literature-based hsa-let-7b levels were higher in malignant patients as well (1.53 fold, P = 0.011). Two miRs differentiated benign wildtype from benign BRCA1 mutation carriers and an additional 8 miRs differentiated metastastic (n = 8) from non-metastatic (n = 41) cases in the validation cohort. Methods: Pre-treatment plasma samples were collected of patients with benign breast disease and breast cancer and divided over a discovery (n = 31) and validation (n = 84) cohort. From the discovery cohort miRs differentially expressed between benign and malignant cases were identified using a 2,000-miR microarray. Literature-based miRs differentiating benign from malignant disease were added. Using RT-qPCR, their expression was investigated in a validation cohort consisting of pre-treatment benign, malignant and metastatic samples. Additionally, benign and malignant cases were compared to benign and malignant cases of BRCA1-mutation carriers. Conclusions: Plasma microRNA levels differed between patients with and without breast cancer, between benign disease from wildtype and BRCA1-mutation carriers and between breast cancer with and without metastases. Hsa-miR-652-5p was validated as a potential biomarker for breast cancer.

20.
J Plast Surg Hand Surg ; 52(4): 245-252, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29806795

RESUMO

INTRODUCTION: Challenges of direct-to-implant breast reconstruction (BR) are to achieve sufficient implant coverage and lower pole projection. We assessed reoperation rates, long-term patient satisfaction and aesthetic outcome after direct-to-implant BR without acellular dermal matrix (ADM) in women with high breast cancer risk. METHODS: Women who underwent bilateral skin or nipple-sparing mastectomy and immediate direct-to-implant BR between 1994 and 2006 completed a survey on reoperations and the Breast-Q Reconstruction questionnaire. Photographs taken during follow-up were rated for long-term aesthetic outcome (scale 1-10) by five plastic surgeons. Outcomes were compared between women who never underwent unanticipated reoperations after immediate BR and women who underwent one or more reoperations, adjusted for potential confounders using multivariable linear regression. RESULTS: Of 143 women, 70 (49%) were never reoperated and 73 (51%) had undergone reoperations. Median follow-up was 12 years in both groups (range 7-17 and 6-19 years, respectively). Baseline characteristics were comparable except for history of prophylactic oophorectomy with 81% in the no-reoperations group versus 66% in the reoperated group (p = .03). Breast-Q scores were 59.7 ± 17.3 versus 58.0 ± 17.8 (p = .67) for 'satisfaction with breasts' and 71.1 ± 20.3 versus 68.1 ± 22.9 (p = .47) for 'satisfaction with outcome' in the no-reoperation versus reoperation group, respectively. Aesthetic outcome was scored 5.8 ± 1.1 in the no-reoperation group versus 5.3 ± 1.3 in the reoperation group (p = .01). CONCLUSIONS: The single-stage intent did not prevent unanticipated surgical reinterventions in 51% of the patients. Long-term patient satisfaction was reasonable and not affected by reoperations. Aesthetic outcome, however, was only poor to reasonable and scores were significantly lower in the reoperated group.


Assuntos
Implante Mamário , Implantes de Mama , Estética , Satisfação do Paciente , Adulto , Implante Mamário/efeitos adversos , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Mastectomia Subcutânea , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Fatores de Risco , Tempo para o Tratamento , Adulto Jovem
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