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PURPOSE: Receptor and subtype discordance between primary breast tumours and metastases is a frequently reported phenomenon. The aim of this article is to review the current evidence on receptor discordance in metastatic breast cancer and to explore the benefit of performing a repeat biopsy in this context. METHODS: Searches were undertaken on PubMed and Clinicaltrials.gov for relevant publications and trials. CONCLUSION: The current guidelines recommend offering to perform a biopsy of a metastatic lesion to evaluate receptor status. The choice of systemic therapy in metastatic disease is often based on the receptor status of the primary lesion. As therapeutic decision making is guided by subtype, biopsy of the metastatic lesion to determine receptor status may alter treatment. This article discusses discordance rates, the mechanisms of receptor discordance, the effect of discordance on treatment and survival outcomes, as well as highlighting some ongoing clinical trials in patients with metastatic breast cancer.
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BACKGROUND: Breast cancer brain metastasis is a rising occurrence, necessitating a better understanding of the mechanisms involved for effective management. Breast cancer brain metastases diverge notably from the primary tumor, with gains in kinase and concomitant losses of steroid signaling observed. In this study, we explored the role of the kinase receptor RET in promoting breast cancer brain metastases and provide a rationale for targeting this receptor. METHODS: RET expression was characterized in a cohort of patients with primary and brain metastatic tumors. RET functionality was assessed using pharmacological inhibition and gene silencing in patient-derived brain metastatic tumor explants and in vivo models, organoid models, and brain organotypic cultures. RNA sequencing was used to uncover novel brain metastatic relevant RET mechanisms of action. RESULTS: A statistically significant enrichment of RET in brain metastases was observed in estrogen receptor-positive breast cancer, where it played a role in promoting cancer cell adhesion, survival, and outgrowth in the brain. In vivo, RET overexpression enhanced brain metastatic competency in patient-derived models. At a mechanistic level, RET overexpression was found to enhance the activation of gene programs involved in cell adhesion, requiring EGFR cooperation to deliver a pro-brain metastatic phenotype. CONCLUSION: Our results illustrate, for the first time, the role of RET in regulating colonization and outgrowth of breast cancer brain metastasis and provide data to support the use of RET inhibitors in the management strategy for patients with breast cancer brain metastases.
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PURPOSE OF REVIEW: Homologous recombination repair deficiency (HRD) increases breast cancer susceptibility and influences both prophylactic and active management of breast cancer. This review evaluates HRD testing and the therapeutic implications of HRD in a global context. RECENT FINDINGS: Ongoing research efforts have highlighted the importance of HRD beyond BRCA1/2 as a potential therapeutic target in breast cancer. However, despite the improved affordability of next-generation sequencing (NGS) and the discovery of PARP inhibitors, economic and geographical barriers in access to HRD testing and breast cancer screening do not allow all patients to benefit from the personalized treatment approach they provide. Advancements in HRD testing modalities and targeted therapeutics enable tailored breast cancer management. However, inequalities in access to testing and optimized treatments are contributing to widening health disparities globally.
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Neoplasias da Mama , Reparo de DNA por Recombinação , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Feminino , Reparo de DNA por Recombinação/genética , Testes Genéticos/métodos , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença , Proteína BRCA2/genética , Proteína BRCA1/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
INTRODUCTION: Appendicectomy remains the standard treatment for appendicitis. There is a lack of clarity on the timeframe in which surgery should be performed to avoid unfavourable outcomes. AIM: To perform a systematic review and network meta-analysis to evaluate the impact the (1)time-of-day surgery is performed (2), time elapsed from symptom onset to hospital presentation (patient time) (3), time elapsed from hospital presentation to surgery (hospital time), and (4)time elapsed from symptom onset to surgery (total time) have on appendicectomy outcomes. METHODS: A systematic review was performed as per PRISMA-NMA guidelines. The time-of-day which surgery was done was divided into day, evening and night. The other groups were divided into < 24 h, 24-48 h and > 48 h. The rate of complicated appendicitis, operative time, perforation, post-operative complications, surgical site infection (SSI), length of stay (LOS), readmission and mortality rates were analysed. RESULTS: Sixteen studies were included with a total of 232,678 patients. The time of day at which surgery was performed had no impact on outcomes. The incidence of complicated appendicitis, post-operative complications and LOS were significantly better when the hospital time and total time were < 24 h. Readmission and mortality rates were significantly better when the hospital time was < 48 h. SSI, operative time, and the rate of perforation were comparable in all groups. CONCLUSION: Appendicectomy within 24 h of hospital admission is associated with improved outcomes compared to patients having surgery 24-48 and > 48 h after admission. The time-of-day which surgery is performed does not impact outcomes.
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Apendicectomia , Apendicite , Tempo de Internação , Humanos , Apendicectomia/métodos , Apendicite/cirurgia , Tempo de Internação/estatística & dados numéricos , Metanálise em Rede , Fatores de Tempo , Complicações Pós-Operatórias , Tempo para o Tratamento , Resultado do Tratamento , Duração da CirurgiaRESUMO
Aim: The overamplification of human epidermal growth factor (HER2) in breast cancer (BC) has been the subject of numerous research publications since its discovery in 1987. This is the first bibliometric analysis (BA) conducted on HER2-positive (HER2+) BC. The purpose of this BA is to analyze the published research on HER2+ BC from 1987 to 2024, highlighting the most significant scientific literature, as well as the main contributing authors and journals, and evaluating the impact of clinical and lab-based publications on HER2+ BC research. Methods: The Web of Science Core Collection (WoSCC) was searched using the terms "Breast cancer" OR "Breast carcinoma" OR "Breast tumor" AND "HER2 positive" OR "HER2+". The search was limited by publication year (1987-2024) and only full English articles were included. WoS returned 7,469 relevant results, and from this dataset, a bibliometric analysis was conducted using the "analyze results" and "journal citation report" functions in WoS and the VOSviewer 1.6.16 software to generate bibliographic coupling and co-citation analysis of authors. Results: The analysis encompassed a total of 7,469 publications, revealing a notable increase in the annual number of publications, particularly in recent years. The United States, China, Italy, Germany, and Spain were the top five most prolific countries. The top five significant institutions that published HER2+ research were the University of Texas System, Unicancer, UTMD Anderson Cancer Center, Harvard University, and University of California System. Breast Cancer Research and Treatment, Clinical Cancer Research, and Clinical Breast Cancer were the top three notable journals with the highest number of HER2+ BC publications. Dennis Slamon (Nc = 45,411, H-index = 51) and Jose Baselga (Nc = 32,592, H-index = 55) were the most prolific authors. Evolving research topics include anti-HER2 therapy in the neoadjuvant setting, treatment of metastatic HER2+ BC, and overcoming therapy resistance. Conclusion: This study provides an overview of HER2+ BC research published over the past three decades. It provides insight into the most cited papers and authors, and the core journals, and identifies new trends. These manuscripts have had the highest impact in the field and reflect the continued evolution of HER2 as a therapeutic target in BC.
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BACKGROUND: Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. METHODS: A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals. RESULTS: A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001). CONCLUSION: The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.
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Neoplasias da Mama , Terapia Neoadjuvante , Feminino , Humanos , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Contagem de Leucócitos , Contagem de Linfócitos , Neutrófilos , Valor Preditivo dos Testes , PrognósticoRESUMO
BACKGROUND: There have been ongoing attempts to de-escalate surgical intervention in older breast cancer patients in recent years. However, there remains ongoing hesitancy amongst surgeons to de-implement axillary staging in this cohort. The supporting argument for performing a sentinel lymph node biopsy (SLNB) is that it may guide subsequent management. METHODS: A retrospective review was performed of 356 SLNBs, in 342 women ≥ 70 years of age with invasive breast cancer, between 2014 and 2022 in a single institution. Data were collected on patient and tumor characteristics and subsequent management for all patients and for patients with ER+/HER2-, early-stage disease. RESULTS: Positive SLNB significantly increased likelihood of receiving adjuvant chemotherapy (CTh) in patients aged 70-75 in all clinical subtypes (OR 4.0, 95% CI, 1.6-10; P = .0035). Positive SLNB did not significantly increase likelihood of receiving adjuvant CTh in patients aged 75-80, however, an Oncotype Dx score of ≥ 26 did (OR 34.50, 95% CI, 3.00-455.2; P = .0103). Positive SLNB was significantly associated with receiving adjuvant radiotherapy (RTh) in all patients aged 70-75 (OR 4.5, 95% CI, 2.0-11; P = .0004) and 75-80 (OR 9.7, 95% CI, 2.7-46; P = .0015). In patients aged ≥ 80 years, positive SLNB did not have a significant influence on subsequent treatments. CONCLUSION: In this study, SLNB did not significantly influence subsequent management decisions in patients over 80 and should rarely be performed in this cohort. However, SLNB still had a role in patients aged 70-80 and should be used selectively in this cohort.
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Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Humanos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Feminino , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Axila , Estadiamento de Neoplasias , Tomada de Decisão Clínica , Metástase Linfática/patologia , Mastectomia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgiaRESUMO
PURPOSE: There are a wide variety of intraoperative techniques available in breast surgery to achieve low rates for positive margins of excision. The objective of this systematic review was to determine the pooled diagnostic accuracy of intraoperative breast margin assessment techniques that have been evaluated in clinical practice. METHODS: This study was performed in accordance with PRISMA guidelines. A systematic search of the literature was conducted to identify studies assessing the diagnostic accuracy of intraoperative margin assessment techniques. Only clinical studies with raw diagnostic accuracy data as compared with final permanent section histopathology were included in the meta-analysis. A bivariate model for diagnostic meta-analysis was used to determine overall pooled sensitivity and specificity. RESULTS: Sixty-one studies were eligible for inclusion in this systematic review and meta-analysis. Cytology demonstrated the best diagnostic accuracy, with pooled sensitivity of 0.92 (95 % CI 0.77-0.98) and a pooled specificity of 0.95 (95 % CI 0.90-0.97). The findings also indicate good diagnostic accuracy for optical spectroscopy, with a pooled sensitivity of 0.86 (95 % CI 0.76-0.93) and a pooled specificity of 0.92 (95 % CI 0.82-0.97). CONCLUSION: Pooled data indicate that optical spectroscopy, cytology and frozen section have the greatest diagnostic accuracy of currently available intraoperative margin assessment techniques. However, long turnaround time for results and their resource intensive nature has prevented widespread adoption of these methods. The aim of emerging technologies is to compete with the diagnostic accuracy of these established techniques, while improving speed and usability.
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Neoplasias da Mama , Cuidados Intraoperatórios , Margens de Excisão , Sensibilidade e Especificidade , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Feminino , Cuidados Intraoperatórios/métodos , Secções Congeladas , Período Intraoperatório , Mastectomia Segmentar/métodosRESUMO
BACKGROUND: Electrosurgical devices are commonly used during mastectomy for simultaneous dissection and haemostasis, and can provide potential benefits regarding vessel and lymphatic ligation. The aim of this prospective RCT was to assess whether using a vessel-sealing device (LigaSure™) improves perioperative outcomes compared with monopolar diathermy when performing simple mastectomy. METHODS: Patients were recruited prospectively and randomized in a 1 : 1 manner to undergo simple mastectomy using either LigaSure™ or conventional monopolar diathermy at a single centre. The primary outcome was the number of days the drain remained in situ after surgery. Secondary outcomes of interest included operating time and complications. RESULTS: A total of 86 patients were recruited (42 were randomized to the monopolar diathermy group and 44 were randomized to the LigaSure™ group). There was no significant difference in the mean number of days the drain remained in situ between the monopolar diathermy group and the LigaSure™ group (7.75 days versus 8.23 days; P = 0.613) and there was no significant difference in the mean total drain output between the monopolar diathermy group and the LigaSure™ group (523.50â ml versus 572.80â ml; P = 0.694). In addition, there was no significant difference in the mean operating time between the groups, for simple mastectomy alone (88.25â min for the monopolar diathermy group versus 107.20â min for the LigaSure™ group; P = 0.078) and simple mastectomy with sentinel lymph node biopsy (107.20â min for the monopolar diathermy group versus 114.40â min for the LigaSure™ group; P = 0.440). CONCLUSION: In this double-blinded single-centre RCT, there was no difference in the total drain output or the number of days the drain remained in situ between the monopolar diathermy group and the LigaSure™ group. REGISTRATION NUMBER: EudraCT 2018-003191-13 BEAUMONT HOSPITAL REC 18/66.
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Neoplasias da Mama , Diatermia , Humanos , Feminino , Mastectomia Simples , Neoplasias da Mama/cirurgia , Estudos Prospectivos , MastectomiaRESUMO
PURPOSE OF REVIEW: In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in the treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss the current uses, limitations, and future directions for PARP inhibitors (PARPis) in the treatment of breast cancer. RECENT FINDINGS: Following the results of the OlympiAD and EMBRACA trials, PARPis were approved in HER2-negative breast cancer with a germline BRCA mutation. We reviewed this class of drugs' mechanism of action, efficacy, and limitations, as well as further studies that discussed resistance, impaired homologous recombination repair (HRR), and the combination of PARPis with other drugs. Improving understanding of HRR, increasing the ability to target resistance, and combining PARPis with other novel agents are continuing to increase the clinical utility of PARPis.
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Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Poli(ADP-Ribose) Polimerases/genética , Reparo do DNA , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
BACKGROUND: The current standard of care in the neoadjuvant setting for high-risk HER2-positive (HER2 +) breast cancer is to combine systemic chemotherapy with dual HER2 blockade, trastuzumab and pertuzumab. Targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer. To improve treatment-associated toxicity, chemotherapy-sparing approaches are currently being investigated. Trastuzumab deruxtecan (T-DXd) is an HER2-directed antibody-drug-conjugate (ADC) with promising results in the metastatic setting for HER2-positive breast cancer. The SHAMROCK study investigates neoadjuvant T-DXd in early stage HER2-positive breast cancer, using pathological complete response (pCR) rate as the primary endpoint. METHODS: This is a phase II open-label, single arm, adaptive multi-centre trial of T-DXd in the neoadjuvant setting in stage 2-3 HER2-positive breast cancer. Eligible patients will receive 5.4 mg/kg of T-DXd intravenously every 3 weeks for up to 6 cycles. A repeat biopsy will performed after 2 cycles for the RNA disruption index (RDI) score assessment. According to their likelihood of pCR, as determined by the RDI score, patients will either undergo 4 or 6 cycles of T-DXd prior to imaging. Patients with imaging complete response (iCR) after either 4 or 6 cycles will proceed to surgery. Patients who do not achieve iCR will either undergo further systemic therapy or proceed to surgery. DISCUSSION: The SHAMROCK study is a chemotherapy-sparing approach to curative intent treatment, investigating neoadjuvant T-DXd. We hypothesise that neoadjuvant T-DXd will have a high pCR rate and be associated low toxicity in early stage HER2-positive breast cancer. TRIAL REGISTRATION: EudraCT Number: 2022-002485-32; ClinicalTrials.gov identifier: NCT05710666; Cancer Trials Ireland study number: CTRIAL-IE 22-01.
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Neoplasias da Mama , Camptotecina/análogos & derivados , Imunoconjugados , Humanos , Feminino , Neoplasias da Mama/patologia , Terapia Neoadjuvante/efeitos adversos , Receptor ErbB-2/análise , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trastuzumab/uso terapêutico , Imunoconjugados/uso terapêutico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
Inflammatory fibroid polyps (IFP) are rare benign neoplasms most commonly occurring within the respiratory tract but are rarely also observed in the gastro-intestinal tract. Herein we present the case of a 73-year-old female presenting with ileo-ileal intussusception secondary to IFP. The patient was treated with emergency laparotomy with segmental bowel resection and primary anastomosis. Histopathological analysis of the excised bowel segment initially revealed a low-grade, mural based spindle cell neoplasm with surrounding benign, reactive lymphadenopathy. Immunohistochemical analysis demonstrated that the lesional cells stained positive for Vimentin, Smooth Muscle Actin (SMA), and CD34. On secondary analysis of the specimen, the morphology and immunohistochemical profile of the mass was in keeping with IFP. No invasive malignancy was identified. Such cases have been previously reported under the pseudonym 'the great mimicker', due to their striking similarity to malignant processes. This case report aims to add to the small body of research reporting such atypical presentations.
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BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela , Excisão de Linfonodo , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Hormônios/uso terapêutico , Axila/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologiaRESUMO
HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype.
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Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
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Anemia , Neoplasias da Mama , Neutropenia , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/efeitos adversos , Camptotecina , Receptor ErbB-2RESUMO
BACKGROUND: Breast cancer surveillance programmes ensure early identification of recurrence which maximises overall survival. Programmes include annual clinical examination and radiological assessment. There remains debate around the value of annual clinical exam in diagnosing recurrent disease/second primaries. The aim was to assess diagnostic modalities for recurrent breast cancer with a focus on evaluating the role of annual clinical examination. PATIENTS AND METHODS: A prospectively maintained database from a symptomatic breast cancer service between 2010-2020 was reviewed. Patients with biopsy-proven recurrence/second breast primary were included. The primary outcome was the diagnostic modality by which recurrences/secondary breast cancers were observed. Diagnostic modalities included (i) self-detection by the patient, (ii) clinical examination by a breast surgeon or (iii) radiological assessment. RESULTS: A total of 233 patients were identified and, following application of exclusion criteria, a total of 140 patients were included. A total of 65/140 (46%) patients were diagnosed clinically, either by self-detection or clinical examination, while 75/140 (54%) were diagnosed radiologically. A total of 59/65 (91%) of patients clinically diagnosed with recurrence presented to the breast clinic after self-detection of an abnormality. Four (6%) patients had cognitive impairment and recurrence was diagnosed by a carer. Two (3%) patients were diagnosed with recurrence by a breast surgeon at clinical examination. The median time to recurrence in all patients was 48 months (range 2-263 months). CONCLUSION: Clinical examination provides little value in diagnosing recurrence (< 5%) and surveillance programmes may benefit from reduced focus on such a modality. Regular radiological assessment and ensuring patients have urgent/easy access to a breast clinic if they develop new symptoms/signs should be the focus of surveillance programmes.
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Neoplasias da Mama , Feminino , Humanos , Instituições de Assistência Ambulatorial , Biópsia , Neoplasias da Mama/diagnóstico , Doença Crônica , SeguimentosRESUMO
Purpose: The development of human epidermal growth factor receptor 2 (HER2)-directed therapies has revolutionized the treatment of HER2-positive breast cancer. The aim of this article is to review the continually evolving treatment strategies in the neoadjuvant setting of HER2-positive breast cancer, as well as the current challenges and future perspectives. Methods: Searches were undertaken on PubMed and Clinicaltrials.gov for relevant publications and trials. Findings: The current standard of care in high-risk HER2-positive breast cancer is to combine chemotherapy with dual anti-HER2 therapy, for a synergistic anti-tumor effect. We discuss the pivotal trials which led to the adoption of this approach, as well as the benefit of these neoadjuvant strategies for guiding appropriate adjuvant therapy. De-escalation strategies are currently being investigated to avoid over treatment, and aim to safely reduce chemotherapy, while optimizing HER2-targeted therapies. The development and validation of a reliable biomarker is essential to enable these de-escalation strategies and personalization of treatment. In addition, promising novel therapies are currently being explored to further improve outcomes in HER2-positive breast cancer.
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BACKGROUND: Sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) in patients with breast cancer who are initially node-positive but convert to clinically/radiologically node-negative remains controversial. The primary aim was to assess pooled 5-year disease-free (DFS) and overall (OS) survival for patients who are initially node-positive but have a negative SLNB after NACT, and do not proceed to axillary lymph node dissection (ALND). METHODS: The study was performed using PRISMA guidelines. A systematic literature search of relevant databases was conducted. The Der Simonian-Laird and Cochran-Mantel-Haenszel methods were used to calculate weighted pooled estimates for OS and DFS for this group compared with patients who had NACT and proceeded to ALND after a negative or positive SLNB. RESULTS: Seven studies involving 915 patients who had a negative SLNB after NACT were included. Pooled estimates of 5-year DFS and OS in patients with a negative SLNB after NACT were 86 (95 per cent c.i. 82.1 to 90.3) and 93.1 (87.8 to 97.0) per cent respectively. Patients with a positive SLNB who underwent ALND had reduced 5-year DFS (OR 0.49, 95 per cent c.i. 0.35 to 0.69; P < 0.001) and OS (OR 0.41, 0.16 to 1.02; P = 0.06) compared with those who had a negative SLNB after NACT. There were no differences in DFS for patients who had a negative SLNB only compared with those undergoing ALND with a pCR (OR 1.65, 0.71 to 3.79; P = 0.24). CONCLUSION: Patients who are initially node-positive and who achieve a complete clinical/radiological axillary response after NACT with a subsequent negative SLNB have high rates of DFS and OS after 5 years. Patients with residual disease have significantly reduced DFS and further axillary treatment may still be warranted.
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Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Terapia Neoadjuvante , Excisão de Linfonodo/métodos , Axila/patologia , Linfonodos/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologiaRESUMO
BACKGROUND: Clinical acumen and experience are critical in the diagnosis of the commonest surgical emergency, acute appendicitis. However, there is an increasing focus on haematological and radiological parameters in reaching the diagnosis of appendicitis, which can negate the importance of clinical findings. The aim was to assess the accuracy of each grade of the surgical team in diagnosing acute appendicitis using clinical acuity alone and compare them to each other as well as validated predictive scores. METHODS: A prospective single-centre study was performed over a six-month period (Dec 2020-May 2021). All patients presenting to the emergency department with right iliac fossa pain were included. RESULTS: A total of 180 patients were included of whom 35% were male. Mean age was 36.2 years (range 16-91). 51.1% had a final diagnosis of appendicitis, of which 91.3% were managed surgically and 8.7% were treated conservatively with antibiotics. Consultants were correct in their prediction of appendicitis in 84.6% of cases (females-83.4%, males-86.6%). Registrars accurately predicted appendicitis in 82.2% of patients (females-80.3%, males-85.7%), whilst house officers (SHOs) and interns were right in 73.8% (females-69.2%, males-82.5%) and 72.7% (females-66.6%, males-83.9%) of cases, respectively. In patients with a histological or radiological diagnosis of appendicitis, the mean Acute Inflammatory Response Score and Acute Appendicitis Score were 7.0 (high risk ≥ 9) and 12.5 (high risk ≥ 16), respectively. Clinicians had superior diagnostic accuracy when compared with both the clinical scores used. CONCLUSION: Seniority was associated with improved diagnostic accuracy in clinically predicting acute appendicitis. This study showed that the clinical judgement of experienced surgeons is more reliable than clinical scores in the diagnosis of appendicitis.