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INTRODUCTION: The optimal combination of radiotherapy and breast reconstruction has not yet been defined. Post-mastectomy radiotherapy (PMRT) has deleterious effects on breast reconstruction, leading to caution amongst surgeons. Pre-operative radiotherapy (PRT) is a growing area of interest, is demonstrated to be safe, and spares autologous flaps from radiotherapy. This study evaluates the aesthetic outcome of PRT and deep inferior epigastric artery perforator (DIEP) flap reconstruction within the Pre-operative Radiotherapy And Deep Inferior Epigastric artery Perforator (DIEP) flAp (PRADA) cohort. METHODS: PRADA was an observational cohort study designed to evaluate the feasibility and safety of PRT for women undergoing neoadjuvant chemotherapy and DIEP reconstruction. Panel evaluation of 3D surface images (3D-SIs) and patient-reported outcome measures (BREAST-Q) for a subset of women in the study were compared with those of a DIEP-PMRT cohort who had undergone DIEP reconstruction and PMRT. RESULTS: Seventeen out of 33 women from the PRADA study participated in this planned substudy. Twenty-eight women formed the DIEP-PMRT cohort (median follow-up 23 months). The median (inter-quartile range [IQR]) 'satisfaction with breasts' score at 12 months for the PRADA cohort was significantly better than the DIEP-PMRT cohort (77 [72-87] versus 64 [54-71], respectively), p=0.01). Median [IQR] panel evaluation (5-point scale) was also significantly better for the PRADA cohort than for the DIEP-PMRT cohort (4.3 [3.9-4.6] versus 3.6 [2.8-4] p=0.003). CONCLUSIONS: Aesthetic outcome for the PRADA cohort was reported to be 'good' or 'excellent' in 93% of cases using a bespoke panel assessment with robust methodology. Patient satisfaction at one year is encouraging and superior to DIEP-PMRT at 23 months. Switching surgery-radiotherapy sequencing leads to similar breast aesthetic outcomes and warrants further large-scale, multi-centre evaluation in a randomised trial.
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Neoplasias de la Mama , Mamoplastia , Colgajo Perforante , Femenino , Humanos , Satisfacción del Paciente , Mastectomía/métodos , Arterias Epigástricas/cirugía , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Colgajo Perforante/irrigación sanguínea , Mamoplastia/métodos , Estética , Estudios RetrospectivosRESUMEN
BACKGROUND: Following therapeutic mammoplasty (TM), the contralateral breast may require a later balancing procedure to optimize shape and symmetry. The alternative is to offer patients simultaneous TM with immediate contralateral symmetrization via a dual-surgeon approach, with the goal of reducing costs and minimizing the number of subsequent hospital appointments in an era of COVID-19 surges. The aim of this cost-consequence analysis is to characterize the cost-benefit of immediate bilateral symmetrization dual-operator mammoplasty versus staged unilateral single operator for breast cancer surgery. METHOD: A prospective single-centre observational study was conducted at an academic teaching centre for breast cancer surgery in the UK. Pseudonymized data for clinicopathological variables and procedural care information, including the type of initial breast-conserving surgery and subsequent reoperation(s), were extracted from the electronic patient record. Financial data were retrieved using the Patient-Level Information and Costing Systems. RESULTS: Between April 2014 and March 2020, 232 women received either immediate bilateral (n = 44), staged unilateral (n = 57) for breast cancer, or unilateral mammoplasty alone (n = 131). The median (interquartile range (i.q.r.)) additional cost of unilateral mammoplasty with staged versus immediate bilateral mammoplasty was 5500 (4330 to 6570) per patient (P < 0.001), which represents a total supplementary financial burden of 313 462 to the study institution. There was no significant difference between groups in age, Charlson comorbidity index, operating minutes, time to adjuvant radiotherapy in months, or duration of hospital stay. CONCLUSION: Synchronous dual-surgeon immediate bilateral TM can deliver safe immediate symmetrization and is financially beneficial, without delay to receipt of adjuvant therapy, or additional postoperative morbidity.
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Neoplasias de la Mama , COVID-19 , Mamoplastia , Neoplasias de la Mama/patología , Femenino , Humanos , Mamoplastia/métodos , Mastectomía Segmentaria/métodos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Re-operation due to disease being inadvertently close to the resection margin is a major challenge in breast conserving surgery (BCS). Indocyanine green (ICG) fluorescence imaging could be used to visualize the tumor boundaries and help surgeons resect disease more efficiently. In this work, ICG fluorescence and color images were acquired with a custom-built camera system from 40 patients treated with BCS. Images were acquired from the tumor in-situ, surgical cavity post-excision, freshly excised tumor and histopathology tumour grossing. Fluorescence image intensity and texture were used as individual or combined predictors in both logistic regression (LR) and support vector machine models to predict the tumor extent. ICG fluorescence spectra in formalin-fixed histopathology grossing tumor were acquired and analyzed. Our results showed that ICG remains in the tissue after formalin fixation. Therefore, tissue imaging could be validated in freshly excised and in formalin-fixed grossing tumor. The trained LR model with combined fluorescence intensity (pixel values) and texture (slope of power spectral density curve) identified the tumor's extent in the grossing images with pixel-level resolution and sensitivity, specificity of 0.75 ± 0.3, 0.89 ± 0.2.This model was applied on tumor in-situ and surgical cavity (post-excision) images to predict tumor presence.
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Neoplasias de la Mama , Verde de Indocianina , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Fluorescencia , Formaldehído , Humanos , Márgenes de Escisión , Mastectomía Segmentaria/métodos , Imagen Óptica/métodosRESUMEN
BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research.
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Neoplasias de la Mama , Mamoplastia , Colgajo Perforante , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Estudios de Factibilidad , Femenino , Humanos , Masculino , Mamoplastia/efectos adversos , Mastectomía/efectos adversos , Colgajo Perforante/cirugía , Estudios Prospectivos , Calidad de Vida , Medicina EstatalRESUMEN
OBJECTIVE: A simulator to enable safe practice and assessment of ALND has been designed, and face, content and construct validity has been investigated. SUMMARY AND BACKGROUND DATA: The reduction in the number of ALNDs conducted has led to decreased resident exposure and confidence. METHODS: A cross-sectional multicenter observational study was carried out between July 2017 and August 2018. Following model development, 30 surgeons of varying experience (n = "experts," n = 11 "senior residents," and n = 10 "junior residents") were asked to perform a simulated ALND. Face and content validity questionnaires were administered immediately after ALND. All ALND procedures were retrospectively assessed by 2 attending breast surgeons, blinded to operator identity, using a video-based assessment tool, and an end product assessment tool. RESULTS: Statistically significant differences between groups were observed across all operative subphases on the axillary clearance assessment tool (P < 0.001). Significant differences between groups were observed for overall procedure quality (P < 0.05) and total number of lymph nodes harvested (P < 0.001). However, operator grade could not be distinguished across other end product variables such as axillary vein damage (P = 0.864) and long thoracic nerve injury (P = 0.094). Overall, participants indicated that the simulator has good anatomical (median score >7) and procedural realism (median score >7). CONCLUSIONS: Video-based analysis demonstrates construct validity for ALND assessment. Given reduced ALND exposure, this simulation is a useful adjunct for both technical skills training and formative Deanery or Faculty administered assessments.
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Competencia Clínica , Escisión del Ganglio Linfático/normas , Axila , Estudios Transversales , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns. METHODS: A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used. RESULTS: Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer. CONCLUSION: Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise.
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Linfedema del Cáncer de Mama , Neoplasias de la Mama , Linfedema , Cirujanos , Linfedema del Cáncer de Mama/etiología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Femenino , Humanos , Ganglios Linfáticos , Linfedema/etiología , Linfedema/prevención & control , Estados UnidosRESUMEN
BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.
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Neoplasias de la Mama , Verde de Indocianina , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Márgenes de Escisión , Mastectomía Segmentaria , Estudios ProspectivosRESUMEN
INTRODUCTION: Conventional methods for axillary sentinel lymph node biopsy (SLNB) are fraught with complications such as allergic reactions, skin tattooing, radiation, and limitations on infrastructure. A novel technique has been developed for lymphatic mapping utilizing fluorescence imaging. This meta-analysis aims to compare the gold standard blue dye and radioisotope (BD-RI) technique with fluorescence-guided SLNB using indocyanine green (ICG). METHODS: This study was registered with PROSPERO (CRD42019129224). The MEDLINE, EMBASE, Scopus, and Web of Science databases were searched using the Medical Subject Heading (MESH) terms 'Surgery' AND 'Lymph node' AND 'Near infrared fluorescence' AND 'Indocyanine green'. Studies containing raw data on the sentinel node identification rate in breast cancer surgery were included. A heterogeneity test (using Cochran's Q) determined the use of fixed- or random-effects models for pooled odds ratios (OR). RESULTS: Overall, 1748 studies were screened, of which 10 met the inclusion criteria for meta-analysis. ICG was equivalent to radioisotope (RI) at sentinel node identification (OR 2.58, 95% confidence interval [CI] 0.35-19.08, p < 0.05) but superior to blue dye (BD) (OR 9.07, 95% CI 6.73-12.23, p < 0.05). Furthermore, ICG was superior to the gold standard BD-RI technique (OR 4.22, 95% CI 2.17-8.20, p < 0.001). CONCLUSION: Fluorescence imaging for axillary sentinel node identification with ICG is equivalent to the single technique using RI, and superior to the dual technique (RI-BD) and single technique with BD. Hospitals using RI and/or BD could consider changing their practice to ICG given the comparable efficacy and improved safety profile, as well as the lesser burden on hospital infrastructure.
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Neoplasias de la Mama , Ganglio Linfático Centinela , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Colorantes , Femenino , Fluorescencia , Humanos , Verde de Indocianina , Imagen Óptica , Radioisótopos , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático CentinelaRESUMEN
The coronavirus disease-2019 pandemic has had a significant impact on the delivery of surgical services, particularly reconstructive surgery. This article examines the current evidence to assess the feasibility of recommencing immediate breast reconstruction services during the pandemic and highlights considerations required to ensure patient safety.
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Infecciones por Coronavirus/epidemiología , Mamoplastia , Pandemias , Neumonía Viral/epidemiología , Betacoronavirus , Neoplasias de la Mama/cirugía , COVID-19 , Protocolos Clínicos , Infecciones por Coronavirus/transmisión , Infección Hospitalaria/prevención & control , Estudios de Factibilidad , Femenino , Humanos , Mamoplastia/efectos adversos , Mamoplastia/métodos , Mastectomía , Selección de Paciente , Neumonía Viral/transmisión , Complicaciones Posoperatorias , Medición de Riesgo , SARS-CoV-2 , Factores de TiempoRESUMEN
Nipple reconstructions are prone to a variable and unpredictable degree of flattening, which in some cases lead to secondary reconstruction. The use of an acellular dermal matrix (ADM) augmentation may be appropriate in cases with very thin dermis that are particularly prone to flattening or in revision cases where the first procedure has already failed. The authors present a series of 13 nipple reconstructions in ten cases. Average projection at 12 months was 51% in primary cases and 46% in secondary revision cases. This represents a better than expected long term result in a difficult cohort of patients.
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Neoplasias de la Mama/terapia , Ganglios Linfáticos/trasplante , Vasos Linfáticos/cirugía , Linfedema/terapia , Venas/cirugía , Anastomosis Quirúrgica , Axila , Vendajes de Compresión , Ejercicio Físico , Terapia por Ejercicio , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Linfedema/diagnóstico por imagen , Linfedema/etiología , Linfedema/prevención & control , Drenaje Linfático Manual , Microcirugia , Medición de Riesgo , Conducta de Reducción del Riesgo , Cuidados de la PielRESUMEN
CONTEXT: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. AIM: The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. RESULTS: There were 61 such cases (51 males, 10 females). The age range was 7-78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). CONCLUSION: Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported.
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Neoplasias del Ano/complicaciones , Neoplasias de la Mama/complicaciones , Carcinoma de Células Escamosas/complicaciones , Infecciones por VIH/complicaciones , Linfoma no Hodgkin/complicaciones , Adolescente , Adulto , Anciano , Linfoma de Burkitt/complicaciones , Niño , Femenino , Humanos , India , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Centros de Atención Terciaria , Adulto JovenAsunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Mastectomía , Dermis Acelular , Implantes de Mama , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Femenino , Humanos , Mamoplastia/efectos adversos , Mastectomía/efectos adversos , Mastectomía/psicología , Radioterapia Adyuvante , Colgajos Quirúrgicos , Factores de TiempoRESUMEN
Oestrogen receptor α (ERα) is a nuclear receptor that is the driving transcription factor expressed in the majority of breast cancers. Recent studies have demonstrated that the liver receptor homolog-1 (LRH-1), another nuclear receptor, regulates breast cancer cell proliferation and promotes motility and invasion. To determine the mechanisms of LRH-1 action in breast cancer, we performed gene expression microarray analysis following RNA interference for LRH-1. Interestingly, gene ontology (GO) category enrichment analysis of LRH-1-regulated genes identified oestrogen-responsive genes as the most highly enriched GO categories. Remarkably, chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) to identify genomic targets of LRH-1 showed LRH-1 binding at many ERα binding sites. Analysis of select binding sites confirmed regulation of ERα-regulated genes by LRH-1 through binding to oestrogen response elements, as exemplified by the TFF1/pS2 gene. Finally, LRH-1 overexpression stimulated ERα recruitment, while LRH-1 knockdown reduced ERα recruitment to ERα binding sites. Taken together, our findings establish a key role for LRH-1 in the regulation of ERα target genes in breast cancer cells and identify a mechanism in which co-operative binding of LRH-1 and ERα at oestrogen response elements controls the expression of oestrogen-responsive genes.
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Neoplasias de la Mama/genética , Receptor alfa de Estrógeno/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptores Citoplasmáticos y Nucleares/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Células COS , Chlorocebus aethiops , Femenino , Células MCF-7 , Elementos de RespuestaRESUMEN
Estrogen receptor-α (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer.
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Neoplasias de la Mama/fisiopatología , Regulación Neoplásica de la Expresión Génica , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Estrógenos/metabolismo , Secuencia de Aminoácidos , Animales , Aromatasa/metabolismo , Secuencia de Bases , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Células COS , Línea Celular Tumoral , Proliferación Celular , Chlorocebus aethiops , Femenino , Orden Génico , Células Hep G2 , Humanos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Estrógenos/genética , Alineación de SecuenciaRESUMEN
Estrogen receptor-α (ERα) positive breast cancer frequently responds to inhibitors of ERα activity, such as tamoxifen, and/or to aromatase inhibitors that block estrogen biosynthesis. However, many patients become resistant to these agents through mechanisms that remain unclear. Previous studies have shown that expression of ERα in ERα-negative breast cancer cell lines frequently inhibits their growth. In order to determine the consequence of ERα over-expression in ERα-positive breast cancer cells, we over-expressed ERα in the MCF-7 breast cancer cell line using adenovirus gene transduction. ERα over-expression led to ligand-independent expression of the estrogen-regulated genes pS2 and PR and growth in the absence of estrogen. Interestingly, prolonged culturing of these cells in estrogen-free conditions led to the outgrowth of cells capable of growth in cultures from ERα transduced, but not in control cultures. From these cultures a line, MLET5, was established which remained ERα-positive, but grew in an estrogen-independent manner. Moreover, MLET5 cells were inhibited by anti-estrogens showing that ERα remains important for their growth. Gene expression microarray analysis comparing MCF-7 cells with MLET5 highlighted apoptosis as a major functional grouping that is altered in MLET5 cells, such that cell survival would be favoured. This conclusion was further substantiated by the demonstration that MLET5 show resistance to etoposide-induced apoptosis. As the gene expression microarray analysis also shows that the apoptosis gene set differentially expressed in MLET5 is enriched for estrogen-regulated genes, our findings suggest that transient over-expression of ERα could lead to increased cell survival and the development of estrogen-independent growth, thereby contributing to resistance to endocrine therapies in breast cancer patients.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Resistencia a Antineoplásicos , Receptor alfa de Estrógeno/metabolismo , Estrógenos/farmacología , Adenoviridae/genética , Antineoplásicos Hormonales/uso terapéutico , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Neoplasias de la Mama/genética , Ciclo Celular , Receptor alfa de Estrógeno/genética , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tamoxifeno/uso terapéutico , Células Tumorales CultivadasRESUMEN
OBJECTIVES: The smear technique is challenging for a neuropathologist where rapid and accurate diagnosis is to be given on small biopsies. The present study, a large retrospective analysis of squash smears in neurosurgical practice, was conducted to assess the usefulness, accuracy and the diagnostic pitfalls of smear diagnosis. METHODS: The authors analysed 3057 central nervous system (CNS) lesions sent for intraoperative cytology (IC) during the years 1988-2005. The stain used was 1% alcoholic toluidine blue. The smear diagnosis was compared with the histological diagnosis to evaluate the diagnostic accuracy. RESULTS: Diagnostic accuracy irrespective of lesion and site ranged from 83.0% to 86.0% per year (mean=85%). The highest rate of correlation among common brain tumours was noted in schwannoma (96.6%) and pituitary adenoma (92.2%), followed by meningiomas (88.9%), astrocytomas (88.4%), chordomas (86.4%) and neurocytomas (86.9%). Infections as a whole contributed 380 cases. The most common infection was tuberculosis. CONCLUSION: This is the largest series reported from India to the best of our knowledge. Squash smear technique is a very reliable and rapid method of intraoperative diagnosis. Knowledge of clinical and neuroimaging details helps the experienced neuropathologist to improve the diagnostic accuracy.