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Article ; Online: Which lesions with a radiological or core biopsy diagnosis of fibroadenoma should be excised?

Lee, Ahs / James, J / Whisker, L / Rakha, E A / Ellis, I O

Annals of the Royal College of Surgeons of England

2021 Volume 104, Issue 5, Page(s) 361–366

Abstract: Introduction: A recent Association of Breast Surgery summary statement on fibroadenoma management recommends excision only for cellular fibroepithelial lesions and rapidly growing lesions with a core biopsy diagnosis of fibroadenoma; persistent pain is ... ...

Abstract	Introduction: A recent Association of Breast Surgery summary statement on fibroadenoma management recommends excision only for cellular fibroepithelial lesions and rapidly growing lesions with a core biopsy diagnosis of fibroadenoma; persistent pain is a relative indication for excision. Methods: This retrospective study looked at the impact this approach would have on the diagnosis of phyllodes tumours. Results: From 2014 to 2018, there were 1,058 core biopsy diagnoses of fibroadenoma; 112 lesions were excised, of which 98 were fibroadenomas, 4 were hamartomas and 10 were phyllodes tumours. In this group, an excision diagnosis of phyllodes tumour was associated with size more than 40 mm, age more than 40 years and radiological suspicion of phyllodes tumour or carcinoma. One hundred and sixty-six excised fibroepithelial lesions with no previous core biopsy included eight phyllodes tumours; in this group, rapid growth was associated with phyllodes tumour diagnosis. Twelve of the 26 fibroepithelial lesions classified as B3 (cellular fibroepithelial lesion or phyllodes tumour) were diagnosed as phyllodes tumours on excision. Using a combination of radiological, clinical and pathological features it was possible to create an excision policy that would recommend excision of 22 of the 31 phyllodes tumours in this period. Eight of the nine 'missed' phyllodes tumours were benign. Conclusion: The Association of Breast Surgery summary statement will reduce the number of fibroadenomas excised, but may also result in delayed diagnosis of some phyllodes tumours. Appropriate safety netting advice should be provided to identify rapidly growing lesions.
MeSH term(s)	Adult ; Biopsy, Large-Core Needle ; Breast Neoplasms/diagnosis ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Diagnosis, Differential ; Female ; Fibroadenoma/diagnosis ; Fibroadenoma/pathology ; Fibroadenoma/surgery ; Humans ; Phyllodes Tumor/diagnosis ; Phyllodes Tumor/pathology ; Phyllodes Tumor/surgery ; Retrospective Studies
Language	English
Publishing date	2021-12-23
Publishing country	England
Document type	Journal Article
ZDB-ID	80044-2
ISSN	1478-7083 ; 0035-8843
ISSN (online)	1478-7083
ISSN	0035-8843
DOI	10.1308/rcsann.2021.0208
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Article ; Online: Metastatic triple-negative breast cancer.

Rakha, E A / Chan, S

Clinical oncology (Royal College of Radiologists (Great Britain))

2011 Volume 23, Issue 9, Page(s) 587–600

Abstract: The triple-negative class (oestrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) comprises about 15% of breast cancer. It is associated with a poor prognosis compared with tumours that ... ...

Abstract	The triple-negative class (oestrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) comprises about 15% of breast cancer. It is associated with a poor prognosis compared with tumours that are positive for hormone receptors or HER2. Despite being sensitive to chemotherapy, many women with metastatic triple-negative breast cancer (TNBC) relapse quickly, and commonly develop visceral metastasis, including lung, liver and brain metastasis. TNBC has molecular features that overlap with breast cancer in BRCA1 germline mutation carriers and with those of the basal-like molecular class of tumours. Furthermore, tumours with the triple-negative phenotype have specific features and express markers that are potential therapeutic targets, for example an impaired DNA repair mechanism and increased expression of proliferation and basal-associated markers. The presence of these features has important implications for clinical practice and for the design of clinical trials looking at novel therapies. Targeted agents that are currently being investigated include poly (ADP-ribose) polymerase inhibitors, epidermal growth factor receptor inhibitors and anti-angiogenic compounds. Here we discuss the epidemiology, morphological and molecular spectrum of TNBC, the clinical significance of this important class of breast cancer and the current treatment options.
MeSH term(s)	Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Female ; Humans ; Neoplasm Metastasis ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism
Chemical Substances	Receptors, Estrogen ; Receptors, Progesterone ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2011-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1036844-9
ISSN	1433-2981 ; 0936-6555
ISSN (online)	1433-2981
ISSN	0936-6555
DOI	10.1016/j.clon.2011.03.013
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Article ; Online: The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis.

Roxanis, I / Colling, R / Kartsonaki, C / Green, A R / Rakha, E A

Breast cancer research : BCR

2018 Volume 20, Issue 1, Page(s) 11

Abstract: Background: As only a minor portion of the information present in histological sections is accessible by eye, recognition and quantification of complex patterns and relationships among constituents relies on digital image analysis. In this study, our ... ...

Abstract	Background: As only a minor portion of the information present in histological sections is accessible by eye, recognition and quantification of complex patterns and relationships among constituents relies on digital image analysis. In this study, our working hypothesis was that, with the application of digital image analysis technology, visually unquantifiable breast cancer microarchitectural features can be rigorously assessed and tested as prognostic parameters for invasive breast carcinoma of no special type. Methods: Digital image analysis was performed using public domain software (ImageJ) on tissue microarrays from a cohort of 696 patients, and validated with a commercial platform (Visiopharm). Quantified features included elements defining tumour microarchitecture, with emphasis on the extent of tumour-stroma interface. The differential prognostic impact of tumour nest microarchitecture in the four immunohistochemical surrogates for molecular classification was analysed. Prognostic parameters included axillary lymph node status, breast cancer-specific survival, and time to distant metastasis. Associations of each feature with prognostic parameters were assessed using logistic regression and Cox proportional models adjusting for age at diagnosis, grade, and tumour size. Results: An arrangement in numerous small nests was associated with axillary lymph node involvement. The association was stronger in luminal tumours (odds ratio (OR) = 1.39, p = 0.003 for a 1-SD increase in nest number, OR = 0.75, p = 0.006 for mean nest area). Nest number was also associated with survival (hazard ratio (HR) = 1.15, p = 0.027), but total nest perimeter was the parameter most significantly associated with survival in luminal tumours (HR = 1.26, p = 0.005). In the relatively small cohort of triple-negative tumours, mean circularity showed association with time to distant metastasis (HR = 1.71, p = 0.027) and survival (HR = 1.8, p = 0.02). Conclusions: We propose that tumour arrangement in few large nests indicates a decreased metastatic potential. By contrast, organisation in numerous small nests provides the tumour with increased metastatic potential to regional lymph nodes. An outstretched pattern in small nests bestows tumours with a tendency for decreased breast cancer-specific survival. Although further validation studies are required before the argument for routine quantification of microarchitectural features is established, our approach is consistent with the demand for cost-effective methods for triaging breast cancer patients that are more likely to benefit from chemotherapy.
MeSH term(s)	Adult ; Aged ; Breast/diagnostic imaging ; Breast/ultrastructure ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Breast Neoplasms/ultrastructure ; Disease-Free Survival ; Female ; Humans ; Image Processing, Computer-Assisted ; Lymph Nodes/diagnostic imaging ; Lymph Nodes/ultrastructure ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Proportional Hazards Models
Language	English
Publishing date	2018-02-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-018-0934-x
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Article ; Online: Expression of Lamin A/C in early-stage breast cancer and its prognostic value.

Alhudiri, I M / Nolan, C C / Ellis, I O / Elzagheid, A / Rakha, E A / Green, Andrew R / Chapman, C J

Breast cancer research and treatment

2019 Volume 174, Issue 3, Page(s) 661–668

Abstract: Purpose: Lamins A/C, a major component of the nuclear lamina, play key roles in maintaining nuclear integrity, regulation of gene expression, cell proliferation and apoptosis. Reduced lamin A/C expression in cancer has been reported to be a sign of poor ...

Abstract	Purpose: Lamins A/C, a major component of the nuclear lamina, play key roles in maintaining nuclear integrity, regulation of gene expression, cell proliferation and apoptosis. Reduced lamin A/C expression in cancer has been reported to be a sign of poor prognosis. However, its clinical significance in breast cancer remains to be defined. This study aimed to evaluate expression and prognostic significance of lamin A/C in early-stage breast cancer. Methods: Using immunohistochemical staining of tissue microarrays, expression of lamin A/C was evaluated in a large well-characterised series of early-stage operable breast cancer (n = 938) obtained from Nottingham Primary Breast Carcinoma Series. Association of lamin A/C expression with clinicopathological parameters and outcome was evaluated. Results: Positive expression rate of lamin A/C in breast cancer was 42.2% (n = 398). Reduced/loss of expression of lamin A/C was significantly associated with high histological grade (p < 0.001), larger tumour size (p = 0.004), poor Nottingham Prognostic Index score (p < 0.001), lymphovascular invasion (p = 0.014) and development of distant metastasis (p = 0.027). Survival analysis showed that reduced/loss of expression of lamin A/C was significantly associated with shorter breast cancer-specific survival (p = 0.008). Conclusion: This study suggests lamin A/C plays a role in breast cancer and loss of its expression is associated with variables of poor prognosis and shorter outcome.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lamin Type A/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Tissue Array Analysis/methods
Chemical Substances	Biomarkers, Tumor ; LMNA protein, human ; Lamin Type A
Language	English
Publishing date	2019-01-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-018-05092-w
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Article ; Online: An overview of assessment of prognostic and predictive factors in breast cancer needle core biopsy specimens.

Rakha, E A / Ellis, I O

Journal of clinical pathology

2007 Volume 60, Issue 12, Page(s) 1300–1306

Abstract: Needle core biopsy (NCB), as part of triple assessment for preoperative evaluation and diagnosis of breast cancer, is now considered as an established, highly accurate method for diagnosing breast cancer that has replaced either fine needle aspiration ... ...

Abstract	Needle core biopsy (NCB), as part of triple assessment for preoperative evaluation and diagnosis of breast cancer, is now considered as an established, highly accurate method for diagnosing breast cancer that has replaced either fine needle aspiration cytology or excisional biopsy as the initial diagnostic biopsy procedures in many institutions. In addition to its primary role in establishing an accurate histological diagnosis, NCB can potentially provide important additional pathological prognostic information which may be of direct clinical value in certain situations, such as patients being considered for preoperative (neoadjuvant) therapy. With this background in mind we briefly review the current role of NCB in breast cancer diagnosis and then concentrate this review on the usefulness and issues relating to use of this technique in providing accurate, reliable and clinically relevant preoperative prognostic and predictive information in patients with breast cancer.
MeSH term(s)	Biomarkers, Tumor/analysis ; Biopsy, Needle/methods ; Breast Neoplasms/diagnosis ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Female ; Humans ; Lymphatic Metastasis ; Necrosis ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2007-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80261-x
ISSN	1472-4146 ; 0021-9746
ISSN (online)	1472-4146
ISSN	0021-9746
DOI	10.1136/jcp.2006.045377
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Article ; Online: Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: Critical review.

Toss, M / Miligy, I / Thompson, A M / Khout, H / Green, A R / Ellis, I O / Rakha, E A

Breast (Edinburgh, Scotland)

2017 Volume 35, Page(s) 151–156

Abstract: The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic screening and the relatively low risk of progression to invasive disease have raised questions related to overtreatment. Following a review of current DCIS management ... ...

Abstract	The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic screening and the relatively low risk of progression to invasive disease have raised questions related to overtreatment. Following a review of current DCIS management protocols a more conservative approach has been suggested. Clinical trials have been introduced to evaluate the option of avoiding surgical intervention in a proportion of patients with DCIS defined as "low-risk" using certain clinicopathological criteria. These trials can potentially provide evidence-based models of active surveillance (with or without endocrine therapy) as a future management approach. Despite the undisputable fact of our need to address the obvious overtreatment of screen-detected DCIS, some important questions need to be considered regarding these trials including the eligibility criteria and definition of risk, the proportion of patient eligible for inclusion, and the length of time required for proper analysis of the trials' outcome in view of the long-term natural history of DCIS progression particularly the low-risk group. These factors can potentially affect the practicality and future impact of such trials. This review provides critical analysis of current DCIS management trials and highlights critical issues related to their practicality and the expected outcome.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/drug therapy ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Ductal, Breast/surgery ; Clinical Trials as Topic ; Combined Modality Therapy ; Decision Making ; Disease Progression ; Early Detection of Cancer/statistics & numerical data ; Female ; Humans ; Mastectomy, Segmental/statistics & numerical data
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2017-07-22
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1143210-x
ISSN	1532-3080 ; 0960-9776
ISSN (online)	1532-3080
ISSN	0960-9776
DOI	10.1016/j.breast.2017.07.012
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Zs.A 3620: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer.

Aleskandarany, M A / Green, A R / Ashankyty, I / Elmouna, A / Diez-Rodriguez, M / Nolan, C C / Ellis, I O / Rakha, E A

Breast cancer research and treatment

2016 Volume 158, Issue 2, Page(s) 287–295

Abstract: In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The ... ...

Abstract	In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression hot spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), co-efficient of variation, and correlation co-efficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (P < 0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r = 0.98, P < 0.001). In conclusion, assessment of Ki67 expression using HS scoring method on a full-face BC tissue section can represent the primary tumour growth fraction that is likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.
Language	English
Publishing date	2016-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-016-3893-x
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Article ; Online: Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification.

Aleskandarany, Mohammed A / Soria, D / Green, A R / Nolan, C / Diez-Rodriguez, Maria / Ellis, I O / Rakha, E A

Breast cancer research and treatment

2015 Volume 151, Issue 2, Page(s) 325–333

Abstract: Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statistical ...

Abstract	Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statistical approaches analysing complex/dimensional data association with DM/poor prognosis. However, few of them have fulfilled satisfactory evidences for clinical application. This study aimed at building DM risk assessment algorithm for BC patients. A well-characterised series of early invasive primary operable BC (n = 1902), with immunohistochemical expression of a panel of biomarkers (n = 31) formed the material of this study. Decision tree algorithm was computed using WEKA software, utilising quantitative biomarkers' expression and the absence/presence of distant metastases. Fifteen biomarkers were significantly associated with DM, with six temporal subgroups characterised based on time to development of DM ranging from <1 to >15 years of follow-up. Of these 15 biomarkers, 10 had a significant expression pattern where Ki67LI, HER2, p53, N-cadherin, P-cadherin, PIK3CA and TOMM34 showed significantly higher expressions with earlier development of DM. In contrast, higher expressions of ER, PR and BCL2 were associated with delayed occurrence of DM. DM prediction algorithm was built utilising cases informative for the 15 significant markers. Four risk groups of patients were characterised. Three markers p53, HER2 and BCL2 predicted the probability of DM, based on software-generated cut-offs, with a precision rate of 81.1 % for positive predictive value and 77.3 %, for the negative predictive value. This algorithm reiterates the reported prognostic values of these three markers and underscores their central biological role in BC progression. Further independent validation of this pruned panel of biomarkers is therefore warranted.
MeSH term(s)	Algorithms ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/diagnosis ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Decision Trees ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2015-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-015-3406-3
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Article: Cytological assessment of conventional transbronchial fine needle aspiration of lymph nodes

Rakha, E.A / Naik, V / Chaudry, Z / Baldwin, D / Soomro, I.N

Cytopathology. 2010 Feb., v. 21, no. 1

2010

Abstract: E. A. Rakha, V. Naik, Z. Chaudry, D. Baldwin and I. N. Soomro Cytological assessment of conventional transbronchial fine needle aspiration of lymph nodes Transbronchial fine needle aspiration (TBNA) is a minimally invasive bronchoscopic technique that ... ...

Abstract	E. A. Rakha, V. Naik, Z. Chaudry, D. Baldwin and I. N. Soomro Cytological assessment of conventional transbronchial fine needle aspiration of lymph nodes Transbronchial fine needle aspiration (TBNA) is a minimally invasive bronchoscopic technique that allows pathological examination of mediastinal and hilar lymph nodes. The aim of this study was to assess the cytopathological outcome of TBNA. One hundred and eighty-seven patients who underwent TBNA of mediastinal and hilar lesions from May 2000 to June 2007 were reviewed. TBNA results were considered to be adequate if the cytological material revealed a malignant lesion or sufficient number of benign lymphoid cells. In the current study, 40 cases (21.9%) were reported as inadequate. When inadequate tests were excluded, the overall sensitivity and accuracy of TBNA in the diagnosis of malignant lesions were 83.5% and 88.0% respectively. The lowest sensitivity was noted in lymph node involvement by lymphoma. Regarding the workload associated with TBNA cytology, we found that the average number of conventionally prepared cytological slides per case was high (17 slides per case). Our results confirm that conventional TBNA is a sensitive and useful technique but it is relatively expensive and the protocols should be adapted to allow appropriate material to be collected for ancillary diagnostic tests.
Keywords	lymph nodes ; accuracy ; lung neoplasms ; costs and returns
Language	English
Dates of publication	2010-02
Size	p. 27-34.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	1034190-0
ISSN	0956-5507 ; 1350-4037
ISSN	0956-5507 ; 1350-4037
DOI	10.1111/j.1365-2303.2008.00590.x
Database	NAL-Catalogue (AGRICOLA)

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Article: Gigantic recurrent abdominal desmoid tumour: a case report.

Rakha, E A / Kandil, M A / El-Santawe, M G

Hernia : the journal of hernias and abdominal wall surgery

2007 Volume 11, Issue 2, Page(s) 193–197

Abstract: Deeply seated fibromatosis or desmoid tumour (DT) is a rare entity characterized by benign proliferation of fibroblasts. Although non-malignant, this tumour can be life-threatening due to its invasive property and high recurrence rate. We report a unique ...

Abstract	Deeply seated fibromatosis or desmoid tumour (DT) is a rare entity characterized by benign proliferation of fibroblasts. Although non-malignant, this tumour can be life-threatening due to its invasive property and high recurrence rate. We report a unique case of a huge recurrent abdominal DT (36 cm in diameter, 25 kg in weight) that caused pressure necrosis and sloughing of the overlying anterior abdominal wall, and produced a large fungating mass protruding outside the abdomen. Although preoperative neoadjuvant therapies were all ineffective, radical surgical removal of the tumour was successful. The procedure was followed by an excellent clinical recovery and the patient is still alive with no evidence of recurrent disease after a 6-year follow-up. We recommend surgical removal of DT regardless of its size and in particular in cases where there is no or inadequate response to neoadjuvant therapy.
MeSH term(s)	Adult ; Female ; Fibromatosis, Abdominal/pathology ; Fibromatosis, Abdominal/surgery ; Humans ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/surgery
Language	English
Publishing date	2007-04
Publishing country	France
Document type	Case Reports ; Journal Article
ZDB-ID	1388125-5
ISSN	1248-9204 ; 1265-4906
ISSN (online)	1248-9204
ISSN	1265-4906
DOI	10.1007/s10029-006-0165-4
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