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1.
Lancet ; 403(10423): 261-270, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38065194

RESUMEN

BACKGROUND: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. METHODS: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). FINDINGS: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. INTERPRETATION: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. FUNDING: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética , Mastectomía , Mastectomía Segmentaria/métodos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Prospectivos , Radioterapia Adyuvante , Victoria , Anciano
2.
NPJ Breast Cancer ; 9(1): 65, 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37553371

RESUMEN

Internationally, population breast cancer screening is moving towards a risk-stratified approach and requires engagement and acceptance from current and future screening clients. A decision aid ( www.defineau.org ) was developed based on women's views, values, and knowledge regarding risk-stratified breast cancer screening. This study aims to evaluate the impact of the decision aid on women's knowledge, risk perception, acceptance of risk assessment and change of screening frequency, and decision-making. Here we report the results of a pre and post-survey in which women who are clients of BreastScreen Victoria were invited to complete an online questionnaire before and after viewing the decision aid. 3200 potential participants were invited, 242 responded with 127 participants completing both surveys. After reviewing the decision aid there was a significant change in knowledge, acceptance of risk-stratified breast cancer screening and of decreased frequency screening for lower risk. High levels of acceptance of risk stratification, genetic testing and broad support for tailored screening persisted pre and post review. The DEFINE decision aid has a positive impact on acceptance of lower frequency screening, a major barrier to the success of a risk-stratified program and may contribute to facilitating change to the population breast screening program in Australia.

3.
Breast Cancer Res Treat ; 199(2): 221-230, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36966271

RESUMEN

PURPOSE: Mammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US. METHODS: A retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period. RESULTS: 73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had 'minimal signs' with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented. CONCLUSION: Compared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Estudios Retrospectivos , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/epidemiología , Sensibilidad y Especificidad , Detección Precoz del Cáncer/métodos , Australia/epidemiología , Mamografía/métodos , Mama/patología , Medios de Contraste
5.
Cancers (Basel) ; 13(23)2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34885211

RESUMEN

Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDxTM for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 10 years without radiotherapy increased significantly per 5 DS units (TotBE HR:1.5 and InvBE HR:1.5). Continuous DS was prognostic for TotBE risk although categorical DS did not reach significance. Absolute 10-year TotBE and InvBE risks appear sufficiently different to indicate that DCISionRT can aid physicians in selecting individualized adjuvant DCIS treatment strategies. Further analyses are planned in combined cohorts to increase statistical power.

6.
ANZ J Surg ; 91(11): 2411-2417, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34405514

RESUMEN

BACKGROUND: Magseed technology is a recently introduced localisation technique for impalpable breast lesions with possible advantages over traditional techniques. These include improved theatre logistics, flexibility in incision placement and improved patient experience. This multicentre study evaluates the experience of introducing Magseed technology into routine surgical practice. METHODS: A prospective multicentre study of Magseed localised procedures was performed. Insertion data were recorded by the radiologist including lesion characteristics and Magseed insertion accuracy. The surgical team recorded time from insertion to operation, operating time and surgical satisfaction. Pathology results were reviewed for specimen weight and margins. RESULTS: Between February 2019 and June 2020, 100 patients were enrolled. Magseed localised procedures included 18 excisional biopsies, 23 wide local excisions (WLE), 50 WLE with axillary surgery and four cases of Magseed localised breast WLE with Magseed localised axillary surgery. There were three therapeutic mammoplasties and two cases of Magseed localised targeted axillary node dissection alone. A total of 90% of Magseeds were radiologically placed within 5 mm of the target lesion/node. Time between incision and specimen removal was 17 min (range 6-40 min). All breast and axillary Magseeds were successfully identified and retrieved during surgery. The target lesion was identified in the specimen in all cases. A total of 10% of cases required further surgery for pathologically positive margins. Overall, surgeons reported that Magseed localisation was "easy" or "very easy" in 77% of cases. CONCLUSION: Magseed is a reliable, safe and accurate surgical technique that provides logistical advantages and flexibility of surgical approach. The method was well-accepted by all users.


Asunto(s)
Neoplasias de la Mama , Mama , Axila , Mama/diagnóstico por imagen , Mama/cirugía , Neoplasias de la Mama/cirugía , Femenino , Humanos , Ganglios Linfáticos , Fenómenos Magnéticos , Estudios Prospectivos , Tecnología
7.
EMBO J ; 40(11): e107333, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33950524

RESUMEN

To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1+/- tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post-menopausal women. Single-cell profiling of 34 treatment-naive primary tumors, including estrogen receptor (ER)+ , HER2+ , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1+/- tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8+ T cells characterized triple-negative and HER2+ cancers but not ER+ tumors, while all subtypes comprised cycling tumor-associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER+ tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large-scale integration of patient samples provides a high-resolution map of cell diversity in normal and cancerous human breast.


Asunto(s)
Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Heterogeneidad Genética , Glándulas Mamarias Humanas/metabolismo , Análisis de la Célula Individual , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Linfocitos T CD8-positivos/metabolismo , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Glándulas Mamarias Humanas/citología , Glándulas Mamarias Humanas/patología , RNA-Seq , Microambiente Tumoral
8.
J Am Psychoanal Assoc ; 68(2): 217-239, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32363885

RESUMEN

After analytic training, graduates position their newly acquired identity as "psychoanalyst" in the context of their broader career, contemplating whether to start new analytic cases, adapting their new knowledge base to psychotherapy practice, and deciding how to focus their professional and personal interests going forward. Using questionnaires and interviews, the Columbia Postgraduate Analytic Practice Study (CPAPS) has prospectively tracked the career trajectory of 69 of 76 graduates (91%) from the Columbia University Center for Psychoanalytic Training and Research since 2003. In this paper grounded theory is used to identify developmental themes in interviews with analysts who have been followed for at least ten years. Recent graduates are negotiating the following challenges: developing a sense of competence, navigating relationships with colleagues and former supervisors as situations change and roles shift, transitioning into becoming mentors, and balancing the competing responsibilities of professional and personal life. Disillusionment about aspects of training, analytic practice, analysis as a treatment, institute politics, and the field in general emerges as a stark reality, despite a high level of career satisfaction. Educational recommendations include making career development opportunities available and providing a realistic view of both practice realities and expectations of analytic treatment outcome.


Asunto(s)
Selección de Profesión , Psicoanálisis/educación , Psicoterapeutas/educación , Femenino , Humanos , Estudios Longitudinales , Masculino , Estudios Prospectivos , Investigación Cualitativa , Encuestas y Cuestionarios
9.
Int J Psychoanal ; 101(2): 300-319, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-33952046

RESUMEN

Although much has been written about the training and supervising analyst system (TSA), its role in analysts' professional development has not been empirically studied. The Columbia Psychoanalytic Practice Study (CPAPS) is a longitudinal study of the careers of graduates from the Columbia Center for Psychoanalytic Training and Research. Interviews with 29/37 (78%) analysts graduating from 2003-2009 were analyzed using grounded theory. Our research question was: Are Columbia Center graduates interested in becoming TSAs and what factors influence their success in reaching this goal?Many analysts express interest in pursuing TSA appointment (22/29, 76%), however, a vast majority (26/29, 90%) experience challenges with finding cases, finances, and the work involved at a life stage with competing priorities. Fewer graduates become TSAs than express initial interest, suggesting that graduates find alternate pathways for professional development. While it is vital that institutes mentor graduates to take on a variety of postgraduate roles as educators, researchers, clinicians and scholars, our findings suggest that if the TSA qualification process were more user-friendly (less time-consuming, financially viable, and in step with current practice norms) more graduate analysts would sustain their interest in this career path.


Asunto(s)
Psicoanálisis , Humanos , Estudios Longitudinales
10.
Asia Pac J Clin Oncol ; 16(2): e27-e37, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31657879

RESUMEN

OBJECTIVES: The value of a high-risk surveillance program for mutation carriers and women at high familial breast cancer risk has not been extensively studied. A Breast and Ovarian Cancer Risk Management Clinic (BOCRMC) was established at the Royal Melbourne Hospital in 2010 to provide multimodality screening and risk management strategies for this group of women. The aims of this study were to evaluate the program and describe breast cancer diagnoses for BRCA1, BRCA2, and other germline mutation carriers as well as high-risk noncarriers attending the BOCRMC. METHODS: Clinical data from mutation carriers and noncarriers with a ≥25% lifetime risk of developing breast cancer who attended between 2010 and 2018 were extracted from clinic records and compared. The pattern and mode of detection of cancer were determined. RESULTS: A total of 206 mutation carriers and 305 noncarriers attended the BOCRMC and underwent screening on at least one occasion. Median age was 37 years. After a median follow-up of 34 months, 15 (seven invasive) breast cancers were identified in mutation carriers, with seven (six invasive) breast cancers identified in noncarriers. Of these, 20 (90.9%) were detected by annual screening, whereas two (9.1%) were detected as interval cancers (both in BRCA1 mutation carriers). Median size of the invasive breast cancers was 11 mm (range: 1.5-30 mm). The majority (76.9%) were axillary node negative. In women aged 25-49 years, the annualized cancer incidence was 1.6% in BRCA1, 1.4% in BRCA2 mutation carriers, and 0.5% in noncarriers. This compares to 0.06% annualized cancer incidence in the general Australian population. CONCLUSIONS: Screening was effective at detecting early-stage cancers. The incidence of events in young noncarriers was substantially higher than in the general population. This potentially justifies ongoing management through a specialty clinic, although further research to better personalize risk assessment in noncarriers is required.


Asunto(s)
Neoplasias de la Mama/epidemiología , Predisposición Genética a la Enfermedad/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
11.
Breast Cancer Res ; 20(1): 155, 2018 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-30572910

RESUMEN

BACKGROUND: There is a growing interest in delivering more personalised, risk-based breast cancer screening protocols. This requires population-level validation of practical models that can stratify women into breast cancer risk groups. Few studies have evaluated the Gail model (NCI Breast Cancer Risk Assessment Tool) in a population screening setting; we validated this tool in a large, screened population. METHODS: We used data from 40,158 women aged 50-69 years (via the lifepool cohort) participating in Australia's BreastScreen programme. We investigated the association between Gail scores and future invasive breast cancer, comparing observed and expected outcomes by Gail score ranked groups. We also used machine learning to rank Gail model input variables by importance and then assessed the incremental benefit in risk prediction obtained by adding variables in order of diminishing importance. RESULTS: Over a median of 4.3 years, the Gail model predicted 612 invasive breast cancers compared with 564 observed cancers (expected/observed (E/O) = 1.09, 95% confidence interval (CI) 1.00-1.18). There was good agreement across decile groups of Gail scores (χ2 = 7.1, p = 0.6) although there was some overestimation of cancer risk in the top decile of our study group (E/O = 1.65, 95% CI 1.33-2.07). Women in the highest quintile (Q5) of Gail scores had a 2.28-fold increased risk of breast cancer (95% CI 1.73-3.02, p < 0.0001) compared with the lowest quintile (Q1). Compared with the median quintile, women in Q5 had a 34% increased risk (95% CI 1.06-1.70, p = 0.014) and those in Q1 had a 41% reduced risk (95% CI 0.44-0.79, p < 0.0001). Similar patterns were observed separately for women aged 50-59 and 60-69 years. The model's overall discrimination was modest (area under the curve (AUC) 0.59, 95% CI 0.56-0.61). A reduced Gail model excluding information on ethnicity and hyperplasia was comparable to the full Gail model in terms of correctly stratifying women into risk groups. CONCLUSIONS: This study confirms that the Gail model (or a reduced model excluding information on hyperplasia and ethnicity) can effectively stratify a screened population aged 50-69 years according to the risk of future invasive breast cancer. This information has the potential to enable more personalised, risk-based screening strategies that aim to improve the balance of the benefits and harms of screening.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Modelos Estadísticos , Anciano , Área Bajo la Curva , Australia/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Femenino , Humanos , Persona de Mediana Edad , National Cancer Institute (U.S.) , Selección de Paciente , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Estados Unidos
12.
JMIR Form Res ; 2(2): e24, 2018 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-30684421

RESUMEN

BACKGROUND: iPrevent estimates breast cancer (BC) risk and provides tailored risk management information. OBJECTIVE: The objective of this study was to assess the usability and acceptability of the iPrevent prototype. METHODS: Clinicians were eligible for participation in the study if they worked in primary care, breast surgery, or genetics clinics. Female patients aged 18-70 years with no personal cancer history were eligible. Clinicians were first familiarized with iPrevent using hypothetical paper-based cases and then actor scenarios; subsequently, they used iPrevent with their patients. Clinicians and patients completed the System Usability Scale (SUS) and an Acceptability questionnaire 2 weeks after using iPrevent; patients also completed measures of BC worry, anxiety, risk perception, and knowledge pre- and 2 weeks post-iPrevent. Data were summarized using descriptive statistics. RESULTS: The SUS and Acceptability questionnaires were completed by 19 of 20 clinicians and 37 of 43 patients. Usability was above average (SUS score >68) for 68% (13/19) clinicians and 76% (28/37) patients. The amount of information provided by iPrevent was reported as "about right" by 89% (17/19) clinicians and 89% (33/37) patients and 95% (18/19) and 97% (36/37), respectively, would recommend iPrevent to others, although 53% (10/19) clinicians and 27% (10/37) patients found it too long. Exploratory analyses suggested that iPrevent could improve risk perception, decrease frequency of BC worry, and enhance BC prevention knowledge without changing state anxiety. CONCLUSIONS: The iPrevent prototype demonstrated good usability and acceptability. Because concerns about length could be an implementation barrier, data entry has been abbreviated in the publicly available version of iPrevent.

13.
Plant J ; 92(6): 1202-1217, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29024340

RESUMEN

Measuring changes in protein or organelle abundance in the cell is an essential, but challenging aspect of cell biology. Frequently-used methods for determining organelle abundance typically rely on detection of a very few marker proteins, so are unsatisfactory. In silico estimates of protein abundances from publicly available protein spectra can provide useful standard abundance values but contain only data from tissue proteomes, and are not coupled to organelle localization data. A new protein abundance score, the normalized protein abundance scale (NPAS), expands on the number of scored proteins and the scoring accuracy of lower-abundance proteins in Arabidopsis. NPAS was combined with subcellular protein localization data, facilitating quantitative estimations of organelle abundance during routine experimental procedures. A suite of targeted proteomics markers for subcellular compartment markers was developed, enabling independent verification of in silico estimates for relative organelle abundance. Estimation of relative organelle abundance was found to be reproducible and consistent over a range of tissues and growth conditions. In silico abundance estimations and localization data have been combined into an online tool, multiple marker abundance profiling, available in the SUBA4 toolbox (http://suba.live).


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteoma , Proteómica , Biomarcadores/metabolismo , Orgánulos/metabolismo , Transporte de Proteínas
14.
Nat Med ; 22(8): 933-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27322743

RESUMEN

Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.


Asunto(s)
Proteína BRCA1/genética , Conservadores de la Densidad Ósea/farmacología , Neoplasias de la Mama/prevención & control , Mama/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Denosumab/farmacología , Organoides/efectos de los fármacos , Ligando RANK/antagonistas & inhibidores , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Células Madre/efectos de los fármacos , Animales , Conservadores de la Densidad Ósea/uso terapéutico , Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinogénesis/genética , Reparación del ADN , Denosumab/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Citometría de Flujo , Heterocigoto , Humanos , Inmunohistoquímica , Ratones , Terapia Molecular Dirigida , Mutación , Trasplante de Neoplasias , Organoides/metabolismo , Pilocarpina/análogos & derivados , Mastectomía Profiláctica , Ligando RANK/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Madre/metabolismo , Proteínas Supresoras de Tumor , Ensayos Antitumor por Modelo de Xenoinjerto
15.
J Chem Phys ; 144(17): 174104, 2016 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-27155622

RESUMEN

We apply first-principles approaches with Hubbard U corrections for calculation of small molecule binding energetics to open-shell transition metal atoms in metal-organic frameworks (MOFs). Using density functional theory with van der Waals dispersion-corrected functionals, we determine Hubbard U values ab initio through an established linear response procedure for M-MOF-74, for a number of different metal centers (M = Ti, V, Cr, Mn, Fe, Co, Ni, and Cu). While our ab initio U values differ from those used in previous work, we show that they result in lattice parameters and electronic contributions to CO2-MOF binding energies that lead to excellent agreement with experiments and previous results, yielding lattice parameters within 3%. In addition, U-dependent calculations for an example system, Co-MOF-74, suggest that the CO2 binding energy grows monotonically with the value of Hubbard U, with the binding energy shifting 4 kJ/mol (or 0.041 eV) over the range of U = 0-5.4 eV. These results provide insight into an approximate but computationally efficient means for calculation of small molecule binding energies to open-shell transition metal atoms in MOFs and suggest that the approach can be predictive with good accuracy, independent of the cations used and the availability of experimental data.

16.
Breast J ; 22(4): 413-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27095381

RESUMEN

To examine practice patterns for breast cancer patients with limited sentinel node (SN) disease in light of the ACOSOG Z0011 results. Retrospective analysis of patients with T1-2 breast cancer and positive sentinel lymph node biopsy (SLNB) admitted between January 2009 and December 2012. Patient demographics, tumor characteristics, and treatments were recorded. Eight hundred positive SLNBs were identified. A total of 452 (56.5%) proceeded to completion axillary lymph node dissection (cALND). cALND rate decreased from 65.1% to 49.7% from 2009-2010 to 2011-2012. cALND was performed for micrometastasis or isolated tumor cells in 39.3% in 2009-2010 and 22.2% in 2011-2012, whereas for macrometastases the rates were 83.1% and 68.6%, respectively. cALND rates diminished for both Z0011-eligible and -ineligible patients. The ACOSOG Z0011 trial presentation and publication coincided with a reduction in cALND for breast cancer with limited nodal disease. There appears equipoise regarding management of macrometastatic SN disease.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Escisión del Ganglio Linfático/estadística & datos numéricos , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Anciano , Antineoplásicos/uso terapéutico , Australia , Axila/patología , Axila/cirugía , Ensayos Clínicos como Asunto , Femenino , Humanos , Metástasis Linfática/patología , Persona de Mediana Edad , Micrometástasis de Neoplasia/patología , Estudios Retrospectivos
17.
Asia Pac J Clin Oncol ; 11(4): 319-27, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26245952

RESUMEN

AIM: The American Society of Clinical Oncology and US Institute of Medicine emphasize the need to trial novel models of posttreatment care, and disseminate findings. In 2011, the Victorian State Government (Australia) established the Victorian Cancer Survivorship Program (VCSP), funding six 2-year demonstration projects, targeting end of initial cancer treatment. Projects considered various models, enrolling people of differing cancer types, age and residential areas. We sought to determine common enablers of success, as well as challenges/barriers. METHODS: Throughout the duration of the projects, a formal "community of practice" met regularly to share experiences. Projects provided regular formal progress reports. An analysis framework was developed to synthesize key themes and identify critical enablers and challenges. Two external reviewers examined final project reports. Discussion with project teams clarified content. RESULTS: Survivors reported interventions to be acceptable, appropriate and effective. Strong clinical leadership was identified as a critical success factor. Workforce education was recognized as important. Partnerships with consumers, primary care and community organizations; risk stratified pathways with rapid re-access to specialist care; and early preparation for survivorship, self-management and shared care models supported positive project outcomes. Tailoring care to individual needs and predicted risks was supported. Challenges included: lack of valid assessment and prediction tools; limited evidence to support novel care models; workforce redesign; and effective engagement with community-based care and issues around survivorship terminology. CONCLUSION: The VCSP project outcomes have added to growing evidence around posttreatment care. Future projects should consider the identified enablers and challenges when designing and implementing survivorship care.


Asunto(s)
Cuidados Posteriores/organización & administración , Continuidad de la Atención al Paciente/organización & administración , Implementación de Plan de Salud/métodos , Neoplasias/enfermería , Enfermería Oncológica/métodos , Sobrevivientes/psicología , Australia , Humanos , Neoplasias/psicología , Estados Unidos
18.
Surgeon ; 12(3): 158-65, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24548701

RESUMEN

The axilla has long been a focus of clinicians' attention in the management of breast cancer. The approach to the axilla has undergone dramatic changes over the last century, from radical and extended radical excisions, through the introduction of sentinel node biopsy for node negative patients to the current situation where selective management of those with nodal involvement is being introduced. The introduction of lymphatic mapping and sentinel node biopsy in the 1990's has been key to the major changes that have occurred. In less than 20 years it has moved from a hypothesis to a situation where it is the default approach to almost all clinically node negative patients and is being considered in other situations where axillary clearance was previously considered standard. This article reviews the development and introduction of sentinel node biopsy, its current uncertainties and limitations, and possible future developments.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/secundario , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela/métodos , Femenino , Humanos , Metástasis Linfática
19.
Surg Laparosc Endosc Percutan Tech ; 24(1): 62-6, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24487160

RESUMEN

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy (PRA) was popularized by Walz and colleagues as an alternative approach to minimally invasive adrenalectomy, offering less postoperative pain and faster return to normal activity compared with laparoscopic transperitoneal adrenalectomy (LA). The authors have recently changed from LA to PRA in suitable patients and audited their outcomes. METHODS: Data were prospectively collected for 10 patients who underwent PRA, and a chart review and telephone interviews were conducted with 13 consecutive patients who underwent LA by the same surgeon. Patient demographics, tumor characteristics, analgesia use, operative and anesthetic time, length of stay, and complications were recorded. RESULTS: Data were collected for 13 LAs and 10 PRAs. Patients' baseline characteristics, including age, BMI, and tumor size, were similar between the 2 groups. There were no conversions to open surgery, transfusions, or deaths. Operative time was similar between the 2 groups. PRA patients required less, inpatient postoperative opioid analgesia compared with LA patients (median 1.25 vs. 23 mg of intravenous morphine equivalent, P=0.003), and had a shorter length of stay (median 1 vs. 2 d, P<0.001). The median total days on opioids were lower for PRA patients compared with LA patients (0.5 vs. 9 d, P<0.001). CONCLUSION: Our initial results supports previously published findings that PRA is a safe procedure, with a relatively short learning curve, resulting in reduced postoperative analgesia use, and reduced length of hospital stay when compared with the laparoscopic transperitoneal approach.


Asunto(s)
Enfermedades de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía/métodos , Enfermedades de las Glándulas Suprarrenales/patología , Adulto , Anciano , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Proyectos Piloto , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
20.
Front Plant Sci ; 4: 411, 2013 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-24167507

RESUMEN

A key challenge in the area of bioinformatics in the coming decades is the ability to manage the wealth of information that is being generated from the variety of high throughput methodologies currently being undertaken in laboratories across the world. While these approaches have made available large volumes of data to the research community, less attention has been given to the problem of how to intuitively present the data to enable greater biological insights. Recently, an attempt was made to tackle this problem in the area of Arabidopsis proteomics. The model plant has been the target of countless proteomics surveys producing an exhaustive array of data and online repositories. The MASCP Gator is an aggregation portal for proteomic data currently being produced by the community and unites a large collection of specialized resources to a single portal (http://gator.masc-proteomics.org/). Here we describe the latest additions, upgrades and features to this resource further expanding its role into protein modifications and genome sequence variations.

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