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Multimorbidity refers to the presence of two or more chronic diseases and is associated with adverse outcomes for patients. Factors such as an ageing population have contributed to a rise in prevalence of multimorbidity globally; however, multimorbidity is often neglected in clinical guidelines. This is largely because patients with multimorbidity are systematically excluded from clinical trials. Accordingly, there is an urgent need to develop novel biomarkers and methods of prognostication for this cohort of patients. The hallmarks of ageing are now thought to potentiate the pathogenesis of multimorbidity. MicroRNAs are small, regulatory, noncoding RNAs which have been implicated in the pathogenesis and prognostication of numerous chronic diseases; there is a substantial body of evidence now implicating microRNA dysregulation with the different hallmarks of ageing in the aetiology of chronic diseases. This article proposes using the hallmarks of ageing as a framework to develop a panel of microRNAs to assess the prognostic burden of multimorbidity. This putative molecular morbidity score would have many potential applications, including assessing the efficacy of clinical interventions, informing clinical decision making and facilitating wider inclusion of patients with multimorbidity in clinical trials.
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Biomarcadores , MicroRNAs , Humanos , MicroRNAs/genética , Prognóstico , Doença Crônica , Multimorbidade , Envelhecimento/genética , Efeitos Psicossociais da DoençaRESUMO
INTRODUCTION: Invasive lobular carcinoma (ILC) contributes significantly to the global cancer burden and is the most common of the histological "special types" of breast cancer. ILC has unique features setting it apart from the more common invasive ductal carcinoma (IDC). Despite differences, treatment algorithms do not consider histological differences. AIM: To determine the differences in treatment and outcomes of ILC relative to IDC in a strict case-matched cohort study at a tertiary referral, specialist, breast cancer center. METHODS: All Estrogen receptor positive (ER+) ILCs from 1999 to 2015 were matched for; age, tumor size, grade, PR/HER2 status, nodal stage and metastases with ER+ IDCs from the same period. Surgical and systemic treatments were assessed along with overall (OS) and disease-free survival (DFS). RESULTS: 762 cases in total were analyzed (1:1 matching; ILC:IDC). ILC cases were more often treated with mastectomy (37.5% vs. 28.6%, P .009) and those who received breast conserving surgery (BCS) more often had an incomplete resection (30.2% vs. 19.6%, P .01). IDC were more often treated with NACT (5.5% vs. 14.4%, P < .001). Mean DFS were similar between ILC and IDC; 148.3 vs. 141.4 months (P .112) but OS was significantly longer in the ILC group; 165.7 vs. 134 months (P .002). This trend was consistent among the subset of patients undergoing BCS. For ILC undergoing BCS, mean DFS was 129.8 vs. 128.3 months for IDC (P .418) and OS was 155.4 and 110.7 months respectively (P < .001). Incomplete resection at the time of index surgery did not alter the disease free or overall survival in either the ILC or IDC patients to a level that reached statistical significance. CONCLUSION: In this cohort study, the strict matching of ILC and IDCs for a number of prognostic indicators, demonstrates the impact of lobular histology with a clarity not previously observed. ILCs have comparable survival outcomes to patients with IDC but at the expense of more extensive index and revisional surgery. There is a need for awareness of these facts among surgeons and patients for optimal treatment prioritization and provision.
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Breast cancer is a heterogeneous disease highlighted by the presence of multiple tumor variants and the basal-like breast cancer (BLBC) is considered to be the most aggressive variant with limited therapeutics and a poor prognosis. Though the absence of detectable protein and hormonal receptors as biomarkers hinders early detection, the integration of genomic and transcriptomic profiling led to the identification of additional variants in BLBC. The high-throughput analysis of tissue-specific micro-ribonucleic acids (microRNAs/miRNAs) that are deemed to have a significant role in the development of breast cancer also displayed distinct expression profiles in each subtype of breast cancer and thus emerged to be a robust approach for the precise characterization of the BLBC subtypes. The classification schematic of breast cancer is still a fluid entity that continues to evolve alongside technological advancement, and the transcriptomic profiling of tissue-specific microRNAs is projected to aid in the substratification and diagnosis of the BLBC tumor subtype. In this review, we summarize the current knowledge on breast tumor classification, aim to collect comprehensive evidence based on the microRNA expression profiles, and explore their potential as prospective biomarkers of BLBC.
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Robot-assisted axillary lymph node dissection (RALND) has been proposed to improve surgical and oncological outcomes for patients with breast cancer. To perform a systematic review of current literature evaluating RALND in patients with invasive breast cancer. A systematic search was performed in accordance with the PRISMA guidelines. Studies outlining outcomes following RALND were included. Two studies involving 92 patients were included in this review. Of these, 41 underwent RALND using the da Vinci© robotic system (44.57%), and 51 underwent conventional axillary lymph node dissection (CALND) (55.43%). There was no significant difference observed with respect to intra-operative blood loss or duration of procedure in those undergoing CALND and RALND (P > 0.050). One study reported a significant difference in lymphoedema rates in support of RALND (6.67% vs 26.67%, P = 0.038). Overall, data in relation to postoperative fat necrosis (10.00% vs 33.33%, P = 0.028), wound infection rates (3.33% vs. 20.00%, P = 0.044), and wound ≤ 40 mm in length (63.63% vs. 19.05%, P = 0.020) supported RALND. Oncological outcomes were only reported in one of the studies, which concluded that there was no local or metastatic recurrence in either group at 3-month follow-up. These provisional results support RALND as a safe alternative to CALND. Notwithstanding, the paucity of data limits the robustness of conclusions which may be drawn surrounding the adoption of RALND as the standard of care. Further high-quality studies are required to ratify these findings.
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Contemporary breast cancer management includes surgical resection combined with a multimodal approach, including chemotherapy, radiotherapy, endocrine therapy, and targeted therapies. Breast cancer treatment is now personalised in accordance with disease and host factors, which has translated to enhanced outcomes for the vast majority of patients. Unfortunately, the treatment of the disease involves patients developing treatment-induced toxicities, with cardiovascular and metabolic side effects having negative implications for long-term quality-of-life metrics. MicroRNAs (miRNAs) are a class of small non-coding ribonucleic acids that are 17 to 25 nucleotides in length, which have utility in modifying genetic expression by working at a post-transcriptional cellular level. miRNAs have involvement in modulating breast cancer development, which is well described, with these biomarkers acting as important regulators of disease, as well as potential diagnostic and therapeutic biomarkers. This review focuses on highlighting the role of miRNAs as regulators and biomarkers of disease, particularly in breast cancer management, with a specific mention of the potential value of miRNAs in predicting treatment-related cardiovascular toxicity.
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Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Benchmarking , BiomarcadoresRESUMO
PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.
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Antineoplásicos , Neoplasias da Mama , MicroRNA Circulante , MicroRNAs , Neutropenia , Doenças do Sistema Nervoso Periférico , Humanos , Pessoa de Meia-Idade , Feminino , MicroRNA Circulante/genética , MicroRNA Circulante/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Estudos Prospectivos , MicroRNAs/genética , Antineoplásicos/uso terapêutico , Neutropenia/tratamento farmacológico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: No randomised clinical trials (RCTs) have simultaneously compared the safety of open (OA), transperitoneal laparoscopic (TLA), posterior retroperitoneal (PRA), and robotic adrenalectomy (RA) for resecting adrenal tumours. AIM: To evaluate outcomes for OA, TLA, PRA, and RA from RCTs. METHODS: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny. RESULTS: Eight RCTs with 488 patients were included (mean age: 48.9 years). Overall, 44.5% of patients underwent TLA (217/488), 37.3% underwent PRA (182/488), 16.4% underwent RA (80/488), and just 1.8% patients underwent OA (9/488). The mean tumour size was 35 mm in largest diameter with mean sizes of 44.3 mm for RA, 40.9 mm for OA, 35.5 mm for TLA, and 34.4 mm for PRA (P < 0.001). TLA had the lowest blood loss (mean: 50.6 ml), complication rates (12.4%, 14/113), and conversion to open rates (1.3%, 2/157), while PRA had the shortest intra-operative duration (mean: 94 min), length of hospital stay (mean: 3.7 days), lowest visual analogue scale pain scores post-operatively (mean: 3.7), and was most cost-effective (mean: 1728 euros per case). At NMA, there was a significant increase in blood loss for OA (mean difference (MD): 117.00 ml (95% confidence interval (CI): 1.41-230.00)) with similar blood loss observed for PRA (MD: - 10.50 (95% CI: - 83.40-65.90)) compared to TLA. CONCLUSION: LTA and PRA are important contemporary options in achieving favourable outcomes following adrenalectomy. The next generation of RCTs may be more insightful for comparison surgical outcomes following RA, as this approach is likely to play a future role in minimally invasive adrenalectomy. PROSPERO REGISTRATION: CRD42022301005.
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Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Pessoa de Meia-Idade , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Tempo de Internação , Metanálise em Rede , Espaço Retroperitoneal/cirurgia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Traditionally, sentinel lymph node biopsy (SLNB) was performed to inform adjuvant chemotherapy prescription and prognosis in breast cancer. Following RxPONDER, the OncotypeDX Recurrence Score (RS) guides adjuvant chemotherapy prescription for all postmenopausal patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer with 0 to 3 positive lymph nodes (0-3 + LN). AIMS: To establish the oncological safety of omitting SLNB in postmenopausal patients with ER+/HER2- breast cancer indicated to undergo SLNB and to evaluate the primary determinants of chemotherapy prescription for these patients. PATIENTS AND METHODS: A retrospective cohort study was undertaken. Cox regression and Kaplan-Meier analyses were performed. Data analytics was performed using SPSS v26.0. RESULTS: Five hundred and seventy five consecutive patients were included (mean age: 66.5 years, range: 45-96). The median follow-up was 97.2 months (range: 3.0-181.6). Of the 575 patients, just 12 patients had positive SLNB (SLNB+) (2.1%). Using Kaplan-Meier analyses, SLNB+ failed to impact recurrence (P = .766) or mortality (P = .310). However, using Cox regression analyses, SLNB+ independently predicted poorer disease-free survival (hazard ratio: 1.001, 95% confidence interval (95% CI): 1.000-1.001, P = .029). Logistic regression analysis identified RS as the sole predictor of chemotherapy prescription (odds ratio: 1.171, 95% CI: 1.097-1.250, P < .001). CONCLUSION: Omitting SLNB may be safe and justifiable in postmenopausal patients with ER+/HER2- breast cancer with clinically negative axillae. Following RxPONDER, RS is the most important guide of chemotherapy use in these patients and SLNB may be less important than previously perceived. Prospective, randomized clinical trials are required to fully establish the oncological safety of omitting SLNB in this setting.
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Neoplasias da Mama , Linfonodo Sentinela , Humanos , Idoso , Feminino , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Excisão de Linfonodo , Estudos Retrospectivos , Estudos Prospectivos , Pós-Menopausa , Axila/patologia , Linfonodos/patologia , Linfonodo Sentinela/patologiaRESUMO
Identifying patients likely to develop breast cancer recurrence remains a challenge. Thus, the discovery of biomarkers capable of diagnosing recurrence is of the utmost importance. MiRNAs are small, non-coding RNA molecules which are known to regulate genetic expression and have previously demonstrated relevance as biomarkers in malignancy. To perform a systematic review evaluating the role of miRNAs in predicting breast cancer recurrence. A formal systematic search of PubMed, Scopus, Web of Science, and Cochrane databases was performed. This search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist. A total of 19 studies involving 2287 patients were included. These studies identified 44 miRNAs which predicted breast cancer recurrence. Results from nine studies assessed miRNAs in tumour tissues (47.4%), eight studies included circulating miRNAs (42.1%), and two studies assessed both tumour and circulating miRNAs (10.5%). Increased expression of 25 miRNAs were identified in patients who developed recurrence, and decreased expression of 14 miRNAs. Interestingly, five miRNAs (miR-17-5p, miR-93-5p, miR-130a-3p, miR-155, and miR-375) had discordant expression levels, with previous studies indicating both increased and reduced expression levels of these biomarkers predicting recurrence. MiRNA expression patterns have the ability to predict breast cancer recurrence. These findings may be used in future translational research studies to identify patients with breast cancer recurrence to improve oncological and survival outcomes for our prospective patients.
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Neoplasias da Mama , MicroRNA Circulante , MicroRNAs , Pequeno RNA não Traduzido , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estudos Prospectivos , Biomarcadores Tumorais/genéticaRESUMO
Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the phenotype transitions, accounted for mainly by the loss of receptor expression. The origins of basal-like and human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer subtypes have been attributed to genetic and protein modifications in stem-like cells and luminal progenitor cell populations, respectively. The post-transcriptional regulation of protein expression is known to be influenced by microRNAs (miRNAs) that are deemed to be master regulators of several biological processes in breast tumorigenesis and progression. Our objective was to identify the fractions of luminal breast cancer cells that share stemness potentials and marker profiles and to elucidate the molecular regulatory mechanism that drives transitions between fractions, leading to receptor discordances. Established breast cancer cell lines of all prominent subtypes were screened for the expression of putative cancer stem cell (CSC) markers and drug transporter proteins using a side population (SP) assay. Flow-cytometry-sorted fractions of luminal cancer cells implanted in immunocompromised mice generated a pre-clinical estrogen receptor alpha (ERα+) animal model with multiple tumorigenic fractions displaying differential expression of drug transporters and hormone receptors. Despite an abundance of estrogen receptor 1 (ESR1) gene transcripts, few fractions transitioned to the triple-negative breast cancer (TNBC) phenotype with a visible loss of ER protein expression and a distinct microRNA expression profile that is reportedly enriched in breast CSCs. The translation of this study has the potential to provide novel therapeutic miRNA-based targets to counter the dreaded subtype transitions and the failure of antihormonal therapies in the luminal breast cancer subtype.
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Neoplasias da Mama , MicroRNAs , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/metabolismo , MicroRNAs/genética , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Mama/metabolismo , Fenótipo , Receptores de Progesterona/genéticaRESUMO
BACKGROUND: At present, there is no consensus on optimal neck wound closure methods after thyroid and parathyroid surgery. The aim of this study was to perform a systematic review and network meta-analysis of RCTs evaluating the optimal neck closure method after thyroid and parathyroid surgery. METHODS: A frequentist random-effects network meta-analysis was performed for RCTs comparing at least two closure methods according to PRISMA-network meta-analysis guidelines. Analysis was performed using R packages and Shiny. RESULTS: Eighteen RCTs evaluating six closure methods (that is adhesive (28.5 per cent, 404 patients), absorbable subcuticular suture (18.1 per cent, 257 patients), non-absorbable subcuticular suture (16.8 per cent, 238 patients), staples (26.3 per cent, 372 patients), steristrips (8.1 per cent, 115 patients), and conventional suture (2.1 per cent, 30 patients)) in 1416 patients were included. At network meta-analysis, there was no difference in complication, infection, dehiscence, or haematoma rates irrespective of closure method used. Staples reduced closure duration versus absorbable subcuticular suture (mean difference (MD) 8.50, 95 per cent c.i. 6.90 to 10.10) and non-absorbable subcuticular suture (MD 0.30, 95 per cent c.i. 0.23 to 0.37), whereas adhesives (MD -1.05, 95 per cent c.i. -1.31 to -0.79) reduced closure time relative to staples. Cosmesis was improved after non-absorbable subcuticular suture (odds ratio (OR) 3.41, 95 per cent c.i. 1.66 to 7.00) relative to staples. Staples reduced patient satisfaction (OR 0.04, 95 per cent c.i. 0.00 to 0.33) and ability to shower (OR 0.04, 95 per cent c.i. 0.00 to 0.33) relative to adhesives. CONCLUSION: Despite staples decreasing closure times, this advantage is offset by reduced patient satisfaction, ability to shower, and cosmesis compared with patients with wounds closed using adhesives, absorbable subcuticular suture, and non-absorbable subcuticular suture. Therefore, these closure methods are favourable for closing neck wounds due to more acceptable patient-reported outcomes, without compromising the safety of the procedure.
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Técnicas de Sutura , Glândula Tireoide , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Técnicas de Fechamento de FerimentosRESUMO
BACKGROUND: The use of acellular dermal matrices (ADMs) and synthetic mesh as part of implant-based breast reconstruction (IBBR) has been widely adopted. The authors investigated the clinical efficacy and safety of human ADM (HADM), xenograft ADM (XADM), and synthetic mesh as part of IBBR in postmastectomy patients as compared with previous standard implant reconstruction techniques using only a submuscular pocket for coverage. METHODS: A systematic search for randomized controlled trials and observational studies was performed. A frequentist network meta-analysis was conducted using the R packages netmeta and Shiny. RESULTS: Thirty-one of 2375 studies identified met the predefined inclusion criteria. Traditional submuscular placement (no ADM or mesh) had fewer overall complications compared with HADM [OR, 0.51; credible interval (CrI), 0.34 to 0.74], but there was no significant difference between no ADM or mesh and XADM (OR, 0.63; CrI, 0.29 to 1.32) or synthetic mesh (OR, 0.77; CrI, 0.44 to 1.30). No one treatment was superior with regards to implant loss. No ADM or mesh was associated with fewer infectious complications than HADM (OR, 0.6; CrI, 0.39 to 0.89). Both no ADM or mesh (OR, 0.45; CrI, 0.27 to 0.75) and XADM (OR, 0.46; CrI, 0.23 to 0.88) had reduced seroma compared with HADM. CONCLUSIONS: Selecting the appropriate IBBR should evaluate effectiveness, adverse events, and cost. Although it is difficult to select a universal ideal IBBR, evaluation using this network analysis may help guide both physicians and patients in their choice of procedure, especially in the case of HADM, which in this study was shown to be significantly predisposed to complications of infection and seroma. Randomized data are required comparing XADM versus synthetic meshes, given the similar risk profiles but significant cost discrepancy between the techniques.
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Derme Acelular , Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Neoplasias da Mama/etiologia , Mastectomia/efeitos adversos , Mastectomia/métodos , Implantes de Mama/efeitos adversos , Seroma/etiologia , Telas Cirúrgicas/efeitos adversos , Metanálise em Rede , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Implante Mamário/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND: While long-term outcomes have improved for patients with breast cancer, 20% to 30% will still develop recurrence, and identifying these patients remains a challenge. MicroRNAs (miRNAs) are small, noncoding molecules that modulate genetic expression and affect oncogenesis. STUDY DESIGN: This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited patients undergoing neoadjuvant chemotherapy across 8 Irish centers. Predetermined miRNAs were quantified from patient whole blood using quantitative reverse transcriptase polymerase chain reaction. Venous sampling was performed at diagnosis (timepoint 1) and midway during neoadjuvant chemotherapy (timepoint 2 [T2]). miRNA expression profiles were correlated with recurrence-free survival (RFS), disease-free survival (DFS), and overall survival. Data analysis was performed using R v3.2.3. RESULTS: A total of 124 patients were recruited with a median age of 55.0 years. The median follow-up was 103.1 months. Increased miR-145 expression at T2 was associated with improved RFS (hazard ratio 0.00; 95% confidence interval [CI] 0.00 to 0.99; p = 0.050). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved RFS (p = 0.041). Increased miR-145 expression at T2 trended towards significance in predicting improved DFS (hazard ratio 0.00; 95% CI 0.00 to 1.42; p = 0.067). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved DFS (p = 0.012). No miRNAs correlated with overall survival. CONCLUSIONS: ICORG10/11 is the first Irish multicenter, translational research trial evaluating circulatory miRNAs as biomarkers predictive of long-term survival and correlated increased miR-145 expression with enhanced outcomes in early-stage breast cancer. Validation of these findings is required in the next generation of translational research trials.
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Neoplasias da Mama , MicroRNA Circulante , MicroRNAs , Humanos , Pessoa de Meia-Idade , Feminino , MicroRNA Circulante/genética , MicroRNA Circulante/uso terapêutico , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Estudos Prospectivos , Estadiamento de Neoplasias , Biomarcadores Tumorais/genética , Prognóstico , Regulação Neoplásica da Expressão GênicaRESUMO
In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101 patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.
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Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Testes Genéticos , Projetos Piloto , Irlanda , Estudos de Viabilidade , Proteína BRCA2/genética , Proteína BRCA1/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Predisposição Genética para Doença , Mutação em Linhagem GerminativaRESUMO
INTRODUCTION: There is uncertainty surrounding the role of resection as an option for curative treatment of breast cancer with liver metastases (BCLM). AIM: To perform a systematic review and meta-analysis evaluating the role of liver resection for BCLM. METHODS: A systematic review was performed as per PRISMA guidelines. Hazard ratio (HR) for overall survival (OS) and standard error was obtained from each study and expressed using the generic inverse variance method, with a corresponding 95% confidence interval (CI). OS outcomes at 1- 3- and 5-years were expressed as dichotomous variables and pooled as odds ratios (OR) using the Mantel-Haenszel method. RESULTS: Nine studies with 1732 patients were included. Of these, 24.5% underwent surgical resection of BCLM (424/1732) and 75.5% did not (1308/1732). Overall, OS was significantly better among those who underwent surgery versus controls (HR: 0.69, 95% CI: 0.59-0.80, P < 0.00001). Mortality rates were significantly reduced at 1-year (7.5% (10/134) vs 20.3% (79/390), OR: 0.25, 95% CI: 0.08-0.74, P = 0.010) and 5-years (54.0% (190/352) vs 75.3% (940/1249), OR: 0.46, 95% CI: 0.25-0.87, P = 0.020) respectively for those undergoing surgery versus controls. Mortality rates at 3 years after surgery were lower than the control group (19.1% (29/152) vs 53.0% (222/419)), however this failed to achieve statistical significance at meta-analysis (OR: 0.32, 95% CI: 0.09-1.12, P = 0.070). CONCLUSION: Liver resection may be considered at multidisciplinary meetings for those with BCLM and offers a potentially curative option. However, judicious patient selection is crucial prior to making decisions in relation to resection of BCLM.
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Neoplasias da Mama , Neoplasias Hepáticas , Humanos , Feminino , Hepatectomia , Neoplasias Hepáticas/cirurgia , Melanoma Maligno CutâneoRESUMO
INTRODUCTION: Current standard of care for patients diagnosed with "low-risk" ductal carcinoma in situ (DCIS) involves surgical resection. Ongoing phase III clinical trials are hoping to establish the oncological safety of active surveillance (AS) in managing "low-risk" DCIS. AIMS: To evaluate the oncological safety of AS versus surgery for "low-risk" DCIS. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Survival outcomes were expressed as dichotomous variables and reported as odds ratios (OR) with 95% confidence intervals (95% CI) using the Mantel-Haenszel method. RESULTS: Four studies including 9626 patients were included, 3.9% of which were managed using AS (374/9626) and 96.1% with surgery (9252/9626). The mean age of included patients was 50.3 years (range: 30-99 years) and mean follow-up was 6.1 years. Invasive cancer detection after surgery and AS were similar (OR: 0.93, 95% CI: 0.41-2.11, P = 0.860, heterogeneity (I2) = 0%). At 5 years, BCSS (surgery 99.5% vs. AS 98.7%, P = 0.116) and OS (surgery 95.8% vs. AS 95.7%, P = 0.876) were similar for both groups. At 10 years, BCSS (surgery 98.7% vs. AS 98.6%, P = 0.789) and OS (surgery 87.9% vs. AS 90.9%, P = 0.183) were similar for both groups. Overall, 10-year OS outcomes were similar for both management strategies (OR: 0.32, 95% CI: 0.02-6.42, P = 0.460, I2 = 69%). CONCLUSION: This study outlines the provisional oncological safety of AS for cases of "low-risk" DCIS. While survival outcomes were comparable for both management strategies, ratification of these results in the ongoing phase III clinical trials is still required prior to changes to current management strategies. PROSPERO REGISTRATION: CRD42022313241.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Carcinoma Intraductal não Infiltrante/cirurgia , Conduta Expectante , Estudos Longitudinais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologiaRESUMO
INTRODUCTION: Tranexamic acid (TXA) reduces blood loss and blood transfusion requirements in surgery. Seroma and haematoma formation occur as complications of breast surgery. We aimed to perform a meta-analysis evaluating TXA in reducing post-operative haematoma and seroma formation for breast surgery. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Results were expressed as dichotomous variables pooled as odds ratios (OR) with corresponding 95% confidence intervals (CIs) using the Mantel-Haenszel method. RESULTS: Seven studies including 1446 patients were included. There were 1830 breast surgery procedures performed with TXA administered in 797 cases (43.6%). There was a significant reduction in haematoma rates in the TXA group (TXA: 3.184% (22/691) vs Control: 6.787% (64/943), OR: 0.41, 95% CI: 0.20-0.86, P = 0.020). Based on surgical procedure, haematoma rates were similar for TXA and control groups in cancer surgery (P = 0.230). Haematoma rates reduced following TXA use in cosmetic procedures (TXA: 3.807% (15/394) vs. Control: 9.091% (34/374), OR: 0.41, 95% CI: 0.22-0.75, P = 0.004). Haematoma rates were also reduced in procedures where axillary lymph node dissection (ALND) was not performed; in the TXA group, 3.379% (22/651) developed a haematoma versus 6.623% (60/906) in the control group (OR: 0.45, 95% CI 0.27-0.77, P = 0.003). TXA administration did not impact seroma formation or infection rates. CONCLUSION: Perioperative administration of TXA may impact the incidence of haematoma in breast surgery, particularly in cosmetic procedures and procedures without ALND. Well-designed randomised studies are required to determine its true efficacy. TXA has no effect on seroma formation or infection in breast surgery.
Assuntos
Antifibrinolíticos , Neoplasias da Mama , Ácido Tranexâmico , Humanos , Feminino , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Seroma/etiologia , Seroma/prevenção & controle , Perda Sanguínea Cirúrgica/prevenção & controle , Hematoma/prevenção & controle , Neoplasias da Mama/cirurgiaRESUMO
BACKGROUND: Medical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer. METHODS: Data on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller-Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC. RESULTS: 74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811. CONCLUSION: This study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.