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1.
Br J Cancer ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600326

RESUMO

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

2.
BMJ ; 384: e077039, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302129

RESUMO

OBJECTIVE: To explore how the number and type of breast cancers developed after screen detected atypia compare with the anticipated 11.3 cancers detected per 1000 women screened within one three year screening round in the United Kingdom. DESIGN: Observational analysis of the Sloane atypia prospective cohort in England. SETTING: Atypia diagnoses through the English NHS breast screening programme reported to the Sloane cohort study. This cohort is linked to the English Cancer Registry and the Mortality and Birth Information System for information on subsequent breast cancer and mortality. PARTICIPANTS: 3238 women diagnosed as having epithelial atypia between 1 April 2003 and 30 June 2018. MAIN OUTCOME MEASURES: Number and type of invasive breast cancers detected at one, three, and six years after atypia diagnosis by atypia type, age, and year of diagnosis. RESULTS: There was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502). During 19 088 person years of follow-up after atypia diagnosis (until December 2018), 141 women developed breast cancer. Cumulative incidence of cancer per 1000 women with atypia was 0.95 (95% confidence interval 0.28 to 2.69), 14.2 (10.3 to 19.1), and 45.0 (36.3 to 55.1) at one, three, and six years after atypia diagnosis, respectively. Women with atypia detected more recently have lower rates of subsequent cancers detected within three years (6.0 invasive cancers per 1000 women (95% confidence interval 3.1 to 10.9) in 2013-18 v 24.3 (13.7 to 40.1) in 2003-07, and 24.6 (14.9 to 38.3) in 2008-12). Grade, size, and nodal involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of ipsilateral and contralateral cancers. CONCLUSIONS: Many atypia could represent risk factors rather than precursors of invasive cancer requiring surgery in the short term. Women with atypia detected more recently have lower rates of subsequent cancers detected, which might be associated with changes to mammography and biopsy techniques identifying forms of atypia that are more likely to represent overdiagnosis. Annual mammography in the short term after atypia diagnosis might not be beneficial. More evidence is needed about longer term risks.


Assuntos
Neoplasias da Mama , Medicina Estatal , Feminino , Humanos , Estudos de Coortes , Estudos Prospectivos , Detecção Precoce de Câncer/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Mamografia/métodos , Inglaterra/epidemiologia , Programas de Rastreamento
3.
Br J Radiol ; 97(1154): 324-330, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38265306

RESUMO

Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.


Assuntos
Neoplasias da Mama , Tomada de Decisão Clínica , Feminino , Humanos , Consenso , Incerteza , Mama/diagnóstico por imagem , Mama/patologia , Mamografia/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia
5.
Eur J Surg Oncol ; 50(1): 107292, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061151

RESUMO

INTRODUCTION: Breast lesions of uncertain malignant potential (B3) include atypical ductal and lobular hyperplasias, lobular carcinoma in situ, flat epithelial atypia, papillary lesions, radial scars and fibroepithelial lesions as well as other rare miscellaneous lesions. They are challenging to categorise histologically, requiring specialist training and multidisciplinary input. They may coexist with in situ or invasive breast cancer (BC) and increase the risk of subsequent BC development. Management should focus on adequate classification and management whilst avoiding overtreatment. The aim of these guidelines is to provide updated information regarding the diagnosis and management of B3 lesions, according to updated literature review evidence. METHODS: These guidelines provide practical recommendations which can be applied in clinical practice which include recommendation grade and level of evidence. All sections were written according to an updated literature review and discussed at a consensus meeting. Critical appraisal by the expert writing committee adhered to the 23 items in the international Appraisal of Guidelines, Research and Evaluation (AGREE) tool. RESULTS: Recommendations for further management after core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB) diagnosis of a B3 lesion reported in this guideline, vary depending on the presence of atypia, size of lesion, sampling size, and patient preferences. After CNB or VAB, the option of vacuum-assisted excision or surgical excision should be evaluated by a multidisciplinary team and shared decision-making with the patient is crucial for personalizing further treatment. De-escalation of surgical intervention for B3 breast lesions is ongoing, and the inclusion of vacuum-assisted excision (VAE) will decrease the need for surgical intervention in further approaches. Communication with patients may be different according to histological diagnosis, presence or absence of atypia, or risk of upgrade due to discordant imaging. Written information resources to help patients understand these issues alongside with verbal communication is recommended. Lifestyle interventions have a significant impact on BC incidence so lifestyle interventions need to be suggested to women at increased BC risk as a result of a diagnosis of a B3 lesion. CONCLUSIONS: These guidelines provide a state-of-the-art overview of the diagnosis, management and prognosis of B3 lesions in modern multidisciplinary breast practice.


Assuntos
Neoplasias da Mama , Mama , Feminino , Humanos , Biópsia com Agulha de Grande Calibre , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Mamografia/métodos
6.
Biomedicines ; 11(9)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37760817

RESUMO

Background: Tall cell carcinoma of the breast with reversed polarity (TCCRP) is a rare type of invasive breast cancer with overlapping features with papillary thyroid carcinoma and a characteristic molecular profile. Few cases have been reported in the literature since the first case was described in 2003. Case presentation: We present the case of a 41-year-old female with a symptomatic left breast lump. Image-guided core biopsy was diagnosed as triple-negative apocrine carcinoma. Surgical excision revealed an invasive carcinoma with solid papillary pattern, nuclei arranged away from the basement membrane (reversed polarity) and luminal eosinophilic colloid-like material. The tumour was GATA3-, CK5-, CK14- and CK7-positive and TTF1-negative. Specialist opinion and the identification of hotspot mutations in the IDH2 p.Arg172 gene via PCR confirmed the diagnosis of TCCRP. Conclusions: TCCRP is a relatively recently recognised papillary epithelial neoplasm with characteristic morphological features and molecular profile. Due to its rarity, TCCRP can be diagnostically challenging, and features can be mistaken for benign and malignant lesions. Accurate diagnosis is important in effective treatment of this indolent malignant triple-negative breast cancer, which carries an excellent prognosis.

8.
Breast ; 70: 82-91, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37419078

RESUMO

BACKGROUND: Recent clinical evidence showed that breast cancer with low HER2 expression levels responded to trastuzumab deruxtecan therapy. The HER2-low cancers comprise immunohistochemistry (IHC) score 1+ and 2+ ISH non-amplified tumours, currently classified as HER2 negative. Little data exists on the reproducibility of pathologists reporting of HER2-low cancer. PATIENT AND METHODS: Sixteen expert pathologists of the UK National Coordinating Committee for Breast Pathology scored 50 digitally scanned HER2 IHC slides. The overall level of agreement, Fleiss multiple-rater kappa statistics and Cohen's Kappa were calculated. Cases with low concordance were re-scored by the same pathologists after a washout period. RESULTS: Absolute agreement was achieved in 6% of cases, all of which scored 3+. Poor agreement was found in 5/50 (10%) of cases. This was due to heterogeneous HER2 expression, cytoplasmic staining and low expression spanning the 10% cut-off value. Highest concordance (86%) was achieved when scores were clustered as 0 versus others. Improvement in kappa of overall agreement was achieved when scores 1+ and 2+ were combined. Inter-observer agreement was moderate to substantial in the whole cohort but fair to moderate in the HER2-low group. Similarly, consensus-observer agreement was substantial to almost perfect in the whole cohort and moderate to substantial in the HER2-low group. CONCLUSION: HER2-low breast cancer suffers from lower concordance among expert pathologists. While most cases can reproducibly be classified, a small proportion (10%) remained challenging. Refining the criteria for reporting and consensus scoring will help select appropriate patients for targeted therapy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Patologistas , Receptor ErbB-2/metabolismo , Reprodutibilidade dos Testes , Irlanda , Biomarcadores Tumorais , Variações Dependentes do Observador
9.
Oncol Lett ; 25(5): 177, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37033098

RESUMO

Ovarian cancer is a major cause of cancer-related deaths in women. Our previous study highlighted the interaction between cancer cells and the host immune response in solid cancers. The present study aimed to analyse the proportion, density and distribution of T and B lymphocytes within the tumour and surrounding stroma, and their prognostic significance in young women with borderline and malignant ovarian surface epithelial tumours. Full clinicopathological and outcome data were collected for 57 women aged <50 years diagnosed between January 2010 and December 2015. Representative tumour sections were stained for CD3 (T cells) and CD20 (B cells) and tumour-infiltrating lymphocytes (TILs) were scored following the TILs Working Group Recommendations and described as stromal, intra-tumoural, lymphoid aggregates and touching lymphocytes. Data were statistically analysed and the association with clinicopathological variables was assessed. The median age was 41 years and the most common histological type was serous carcinoma (n=21). The risk of malignancy index was a significant predictor of ovarian cancer diagnosis (P<0.05). A total of 15 out of 34 patients with cancer died. There was significantly greater stromal infiltration of CD3 and CD20 TILs (P=0.01 and P=0.03, respectively) and higher intratumoral CD20 expression in ovarian epithelial cancers compared with borderline tumours. The highest CD3 stroma count and density were observed in serous carcinoma, which also exhibited the highest numbers of CD3 and CD20 aggregates. There was no statistically significant difference between touching lymphocytes and tumour histological subtype. There was no significant association between TIL expression and patient survival. The count, distribution and density of T and B lymphocytes in ovarian tumours varied depending on tumour type and invasiveness. Their topographic distribution within the tumour and surrounding stroma did not impact prognosis in young women with ovarian cancer. TIL analysis in an older age group of women with ovarian tumours is ongoing to determine its potential prognostic significance.

10.
Cancers (Basel) ; 15(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36900303

RESUMO

The assessment of PD-L1 expression in TNBC is a prerequisite for selecting patients for immunotherapy. The accurate assessment of PD-L1 is pivotal, but the data suggest poor reproducibility. A total of 100 core biopsies were stained using the VENTANA Roche SP142 assay, scanned and scored by 12 pathologists. Absolute agreement, consensus scoring, Cohen's Kappa and intraclass correlation coefficient (ICC) were assessed. A second scoring round after a washout period to assess intra-observer agreement was carried out. Absolute agreement occurred in 52% and 60% of cases in the first and second round, respectively. Overall agreement was substantial (Kappa 0.654-0.655) and higher for expert pathologists, particularly on scoring TNBC (6.00 vs. 0.568 in the second round). The intra-observer agreement was substantial to almost perfect (Kappa: 0.667-0.956), regardless of PD-L1 scoring experience. The expert scorers were more concordant in evaluating staining percentage compared with the non-experienced scorers (R2 = 0.920 vs. 0.890). Discordance predominantly occurred in low-expressing cases around the 1% value. Some technical reasons contributed to the discordance. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions.

11.
Cell Rep ; 42(3): 112207, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36867531

RESUMO

The immune microenvironment in breast cancer (BCa) is controlled by a complex network of communication between various cell types. Here, we find that recruitment of B lymphocytes to BCa tissues is controlled via mechanisms associated with cancer cell-derived extracellular vesicles (CCD-EVs). Gene expression profiling identifies the Liver X receptor (LXR)-dependent transcriptional network as a key pathway that controls both CCD-EVs-induced migration of B cells and accumulation of B cells in BCa tissues. The increased accumulation oxysterol ligands for LXR (i.e., 25-hydroxycholesterol and 27-hydroxycholesterol) in CCD-EVs is regulated by the tetraspanin 6 (Tspan6). Tspan6 stimulates the chemoattractive potential of BCa cells for B cells in an EV- and LXR-dependent manner. These results demonstrate that tetraspanins control intercellular trafficking of oxysterols via CCD-EVs. Furthermore, tetraspanin-dependent changes in the oxysterol composition of CCD-EVs and the LXR signaling axis play a key role in specific changes in the tumor immune microenvironment.


Assuntos
Neoplasias da Mama , Oxisteróis , Humanos , Feminino , Receptores X do Fígado/metabolismo , Neoplasias da Mama/genética , Oxisteróis/farmacologia , Tetraspaninas , Linfócitos B/metabolismo , Microambiente Tumoral
12.
J Clin Pathol ; 76(4): 234-238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34620607

RESUMO

AIMS: There is little information on the impact of COVID-19 on breast pathologists. This survey assessed the effect of the COVID-19 pandemic on UK and Ireland-based breast pathologists to optimise working environments and ensure preparedness for potential future pandemics. METHODS: A 35-question survey during the first wave of COVID-19 infections in the UK including questions on workload, working practices, professional development, training, health and safety and well-being was distributed to consultant breast pathologists and responses collected anonymously. RESULTS: There were 135 responses from breast pathologists based in the UK and Ireland. Most participants (75.6%) stated that their workload had decreased and their productivity dropped. 86/135 (63.7%) were given the option of working from home and 36% of those who did reported improved efficiency. Multidisciplinary team meetings largely moved to virtual platforms (77.8%) with fewer members present (41.5%). Online education, including webinars and courses, was utilised by 92.6%. 16.3% of pathologists reported shortages of masks, visors or gowns as the the most common health and safety concern. COVID-19 had a significant negative impact on the physical and mental health of 33.3% of respondents. A small number of pathologists (10.4%) were redeployed and/or retrained. CONCLUSION: The UK and Ireland breast pathologists adapted to the rapid change and maintained service delivery despite the significant impact of the pandemic on their working practices and mental health. It is important to apply flexible working patterns and environments that improve productivity and well-being. The changes suggested should be considered for long-term shaping of breast pathology services.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Patologistas , Irlanda/epidemiologia , Pandemias , Inquéritos e Questionários , Reino Unido/epidemiologia
13.
Pathobiology ; 90(1): 31-43, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35705026

RESUMO

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. METHODS: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. RESULTS: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. CONCLUSION: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.


Assuntos
Neoplasias da Mama , Neoplasias Inflamatórias Mamárias , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias Inflamatórias Mamárias/metabolismo , Neoplasias Inflamatórias Mamárias/patologia , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral , Imunofluorescência , Fatores de Transcrição Forkhead/genética , Microambiente Tumoral
14.
J Clin Pathol ; 76(4): 217-227, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36564170

RESUMO

The last UK breast cancer (BC) human epidermal growth factor receptor 2 (HER2) testing guideline recommendations were published in 2015. Since then, new data and therapeutic strategies have emerged. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) published a focused update in 2018 that reclassified in situ hybridisation (ISH) Group 2 (immunohistochemistry (IHC) score 2+and HER2/chromosome enumeration probe 17 (CEP17) ratio ≥2.0 and HER2 copy number <4.0 signals/cell), as well as addressed other concerns raised by previous guidelines. The present article further refines UK guidelines, with specific attention to definitions of HER2 status focusing on eight key areas: (1) HER2 equivocal (IHC 2+) and assignment of the ASCO/CAP ISH group 2 tumours; (2) the definition of the group of BCs with low IHC scores for HER2 with emphasis on the distinction between IHC score 1+ (HER2-Low) from HER2 IHC score 0 (HER2 negative); (3) reporting cases showing HER2 heterogeneity; (4) HER2 testing in specific settings, including on cytological material; (5) repeat HER2 testing, (6) HER2 testing turnaround time targets; (7) the potential role of next generation sequencing and other diagnostic molecular assays for routine testing of HER2 status in BC and (8) use of image analysis to score HER2 IHC. The two tiered system of HER2 assessment remains unchanged, with first line IHC and then ISH limited to IHC equivocal cases (IHC score 2+) but emerging data on the relationship between IHC scores and levels of response to anti-HER2 therapy are considered. Here, we present the latest UK recommendations for HER2 status evaluation in BC, and where relevant, the differences from other published guidelines.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Hibridização in Situ Fluorescente/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Hibridização In Situ , Imuno-Histoquímica , Reino Unido , Biomarcadores Tumorais/análise
15.
Histopathology ; 82(1): 170-188, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36482270

RESUMO

Neoadjuvant chemotherapy (NACT) has become the standard of care for high-risk breast cancer, including triple-negative (TNBC) and HER2-positive disease. As a result, handling and reporting of breast specimens post-NACT is part of routine practice, and it is important for pathologists to recognise the changes in tumour cells, tumour-associated stroma and background breast tissue induced by NACT. Familiarity with characteristic stromal features enables identification of the pre-treatment tumour site and allows confident diagnosis of pathological complete response (pCR) which is important for decisions concerning adjuvant therapy. Neoadjuvant endocrine therapy (NAET) is used less frequently than NACT; however, the SARS-COVID-19 pandemic has changed practice, with increased use as bridging therapy if surgery is delayed. NAET also induces characteristic changes in the tumour and stroma. Changes in the tumour microenvironment following NACT and NAET are also described. Immunotherapy is approved for use in advanced TNBC, and there are several trials exploring its role in early TNBC in the neoadjuvant setting. The current biomarker to determine eligibility for treatment with immune checkpoint inhibitors is programmed death ligand-1 (PD-L1) immunohistochemistry; however, this is complicated by lack of standardisation with different drugs linked to tests using different antibodies with different scoring systems. The situation in the neoadjuvant setting is further complicated by improved pCR rates for PD-L1-positive tumours in both immune therapy and placebo arms. Alternative biomarkers are urgently needed to identify which patients will derive benefit from immunotherapy and key candidates are discussed.


Assuntos
Neoplasias da Mama , COVID-19 , Humanos , Feminino , Terapia Neoadjuvante , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Antígeno B7-H1 , Pandemias , Microambiente Tumoral
16.
Br J Cancer ; 128(3): 474-477, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36434156

RESUMO

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions. The unusual circumstances of the pandemic meant studies such as RECOVERY were opened almost immediately and recruited record numbers of participants. However, trial teams were required to make concessions and adaptations to these studies to ensure recruitment was rapid and broad. As these are relevant to cancer trials that enrol patients with similar risk factors, we have added three new recommendations to our original ten: employing pragmatism such as using focused information sheets and collection of only the most relevant data; minimising negative environmental impacts with paperless systems; and using direct-to-patient communication methods to improve uptake. These recommendations can be applied to all oncology CID trials to improve their inclusivity, uptake and efficiency. Above all, the success of CID studies during the COVID-19 pandemic underscores their efficacy as tools for rapid treatment evaluation.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Consenso , Oncologia
17.
BMJ Open ; 12(12): e061585, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36535720

RESUMO

PURPOSE: The introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive breast cancer. The Sloane Project, a UK prospective cohort study of screen-detected non-invasive breast neoplasia, commenced in 2003 to evaluate the radiological assessment, surgical management, pathology, adjuvant therapy and outcomes for non-invasive breast neoplasia. Long-term follow-up and accurate data collection are essential to examine the clinical impact. Here, we describe the establishment, development and analytical processes for this large UK cohort study. PARTICIPANTS: Women diagnosed with non-invasive breast neoplasia via the UK National Health Service Breast Screening Programme (NHSBSP) from 01 April 2003 are eligible, with a minimum age of 46 years. Diagnostic, therapeutic and follow-up data collected via proformas, complement date and cause of death from national data sources. Accrual for patients with DCIS ceased in 2012 but is ongoing for patients with epithelial atypia/in situ neoplasia, while follow-up for all continues long term. FINDINGS TO DATE: To date, patients within the Sloane cohort comprise one-third of those diagnosed with DCIS within the NHSBSP and are representative of UK practice. DCIS has a variable outcome and confirms the need for longer-term follow-up for screen-detected DCIS. However, the radiology and pathology features of DCIS can be used to inform patient management. We demonstrate validation of follow-up information collected from national datasets against traditional, manual methods. FUTURE PLANS: Conclusions derived from the Sloane Project are generalisable to women in the UK with screen-detected DCIS. The follow-up methodology may be extended to other UK cohort studies and routine clinical follow-up. Data from English patients entered into the Sloane Project are available on request to researchers under data sharing agreement. Annual follow-up data collection will continue for a minimum of 20 years.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Intraductal não Infiltrante/diagnóstico , Estudos Prospectivos , Mastectomia , Estudos de Coortes , Mamografia/métodos , Medicina Estatal , Neoplasias da Mama/diagnóstico , Reino Unido
18.
Ecancermedicalscience ; 16: 1452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405944

RESUMO

Introduction: Androgen receptor (AR) is one of the predominant nuclear hormone receptors in invasive breast cancer and can be explored as a biomarker of response for targeted anti-androgen therapy, especially in the setting of triple negative breast cancer (TNBC). Luminal AR is a distinct subtype amongst TNBC cases following gene expression studies. TNBC is higher in Africans (23%-82%) and African-Americans (29.8%) compared to Caucasian (10%-15%) breast cancer patients; however, there is a paucity of data on AR expression in this population. The aim of this study is to determine the expression of AR and the proportion of AR positive cancers in TNBCs at the Lagos University Teaching Hospital, Lagos, Nigeria. Methodology: Out of 99 reviewed cases, 78 formalin fixed, paraffin embedded TNBC cases were assembled into a tissue microarray, stained and analysed for AR expression using immunohistochemistry. Results: The mean age of the TNBC patients was 49.3 years (range: 20-80 years). The histologic types in this study were invasive carcinoma (no special type) 75.4%; metaplastic carcinoma 21.4%; lobular carcinoma and mucinous carcinoma 1.6% each. Of 61 TNBC cases analysed, 37.7% were AR positive and 62.3% were AR negative, making the latter to become quadruple negative breast cancers. There was a significant association between age and AR expression (p = 0.02). In the subjects that expressed AR positivity, patients below 50 years accounted for 34.8% (8 of 23) while 65.2% (15 of 23) were above 50 years. There was no significant association between AR expression and histologic type or tumour grade. Conclusion: Over a third of this Nigerian TNBC cohort study is AR+. This warrants further exploration of the predictive and prognostic significance of its expression amongst TNBC and the potential for targeted therapy, specifically androgen antagonists to improve the outcome of this disease with limited therapeutic options.

19.
Int J Surg Case Rep ; 99: 107716, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36261938

RESUMO

INTRODUCTION AND IMPORTANCE: Benign osseous metaplasia (BOM) is a rare entity, with only few cases reported in the breast. Here we present an unusual case of pleomorphic lobular carcinoma of the breast infiltrating BOM, discuss potential mimics and review the literature. CASE PRESENTATION: An 86 year-old female presented with right breast lump for two weeks. Clinical examination revealed a palpable mass, associated with skin tethering and nipple inversion. Mammography and ultrasound showed a densely calcified lesion associated with parenchymal distortion. Core biopsy confirmed malignancy and the patient underwent mastectomy and sentinel lymph node biopsy. Histological assessment showed a 45 mm mass of benign bone trabecula infiltrated by invasive grade 2 lobular carcinoma of classic and pleomorphic types with nodal positivity (2/2). The patient received adjuvant radiotherapy to chest wall and axilla for 3 months. She remains well on aromatase inhibitors after 9 months of follow up. CLINICAL DISCUSSION: Few cases of breast BOM have been reported in the literature commonly in association with benign lesions such as fibroadenomas. So far, only two cases associated with invasive classic lobular carcinoma have been reported in the literature. The main differential is metaplastic (mesenchymal/ matrix producing) carcinoma, in which the osseous component is malignant and the cancer if often of a high grade, basal phenotype. CONCLUSION: We present the first case of BOM of the breast associated with invasive pleomorphic lobular carcinoma. Awareness of the entity and distinction from metaplastic carcinoma and malignant phyllodes with heterologous element are important to ensure appropriate patient management.

20.
Br J Cancer ; 127(12): 2125-2132, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224403

RESUMO

BACKGROUND: The diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial. METHODS: We analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project. RESULTS: Microinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0-25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P < 0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P < 0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005). CONCLUSIONS: The higher breast cancer mortality with microinvasion indicates a more aggressive disease.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/cirurgia , Neoplasias da Mama/cirurgia , Mastectomia , Reino Unido
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