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The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor (2018)
Journal Article
Sarwar, M., Syed Khaja, A. S., Aleskandarany, M., Karlsson, R., Althobiti, M., Ødum, N., …Persson, J. L. (2019). The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor. Oncogene, 38(3), 375-389. https://doi.org/10.1038/s41388-018-0438-2

© 2018, The Author(s). Despite recent improvement in adjuvant therapies, triple-negative, and ER + subtypes of breast cancer (BC) with metastatic potentials remain the leading cause of BC-related deaths. We investigated the role of phosphatidylinosi... Read More about The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor.

Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer (2018)
Journal Article
Kurozumi, S., Joseph, C., Sonbul, S., Aleskandarany, M. A., Pigera, M., Alsaleem, M., …Rakha, E. A. (2018). Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer. Breast Cancer Research and Treatment, 172(1), 61–68. https://doi.org/10.1007/s10549-018-4891-y

BACKGROUND: Ras association and pleckstrin homology domains 1 (RAPH1) is involved in cytoskeleton regulation and re-epithelialisation in invasive carcinoma and therefore may play a key role in carcinogenesis and metastasis. We herein investigated the... Read More about Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer.

The spectrum of triple-negative breast disease: high- and low-grade lesions (2018)
Journal Article
Geyer, F. C., Pareja, F., Weigelt, B., Rakha, E., Ellis, I. O., Schnitt, S. J., & Reis-Filho, J. S. (2018). The spectrum of triple-negative breast disease: high- and low-grade lesions. American Journal of Pathology, 187(10), 2139-2151. https://doi.org/10.1016/j.ajpath.2017.03.016

Triple-negative breast cancer is viewed clinically as an aggressive subgroup of breast cancer. In fact, most triple-negative breast cancers are poor-prognosis tumors with a complex genomic landscape. However, triple-negative disease is vastly heterog... Read More about The spectrum of triple-negative breast disease: high- and low-grade lesions.

Impact of breast cancer grade discordance on prediction of outcome (2018)
Journal Article
Rakha, E. A., Aleskandarany, M. A., Toss, M. S., Mongan, N., El-Sayed, M. E., Green, A. R., Ellis, I. O., & Dalton, L. W. (in press). Impact of breast cancer grade discordance on prediction of outcome. Histopathology, https://doi.org/10.1111/his.13709

BACKGROUND: Histological grade is an independent prognostic variable in breast cancer (BC). Previous concordance studies of BC grade have reported moderate levels of agreement; a typical finding in morphological assessment of biological variables. Th... Read More about Impact of breast cancer grade discordance on prediction of outcome.

Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery (2018)
Journal Article
Shipp, D. W., Rakha, E. A., Koloydenko, A. A., Macmillan, R. D., Ellis, I. O., & Notingher, I. (2018). Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery. Breast Cancer Research, 20, https://doi.org/10.1186/s13058-018-1002-2

Background: In over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insuff... Read More about Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery.

Breast cancer intratumour heterogeneity: current status and clinical implications (2018)
Journal Article
Joseph, C., Papadaki, A., Althobiti, M., Alsaleem, M., Aleskandarany, M. A., & Rakha, E. A. (2018). Breast cancer intratumour heterogeneity: current status and clinical implications. Histopathology, 73(5), 717-731. https://doi.org/10.1111/his.13642

Breast cancer (BC) is a heterogeneous disease that varies in presentation, morphological features, behaviour, and response to therapy. High‐throughput molecular profiling studies have revolutionised our understanding of BC heterogeneity, and have dem... Read More about Breast cancer intratumour heterogeneity: current status and clinical implications.

The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response (2018)
Journal Article
Barone, G., Arora, A., Ganesh, A., Abdel-Fatah, T., Moseley, P., Ali, R., Chan, S. Y., Savva, C., Schiavone, K., Carmell, N., Myers, K. N., Rakha, E. A., Madhusudan, S., & Collis, S. J. (2018). The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response. Oncotarget, 9, 29508-29524. https://doi.org/10.18632/oncotarget.25686

Background: Cyclin-Dependent Kinases (CDKs) are established anti-cancer drug targets and a new generation of CDK inhibitors are providing clinical benefits to a sub-set of breast cancer patients. We have recently shown that human CDK18 promotes effic... Read More about The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response.

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ (2018)
Journal Article
Miligy, I. M., Gorringe, K. L., Toss, M. S., Al-Kawaz, A., Simpson, P., Diez-Rodriguez, M., …Rakha, E. (2018). Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ. Modern Pathology, 31(12), 1807-1815. https://doi.org/10.1038/s41379-018-0086-7

Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behaviour, but they are insufficient to define high risk patients for disease progression precisely. Thioredoxin interacting protein (TXNIP) is a key play... Read More about Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ.

Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion (2018)
Journal Article
Sonbul, S. N., Aleskandarany, M. A., Kurozumi, S., Joseph, C., Toss, M. S., Diez-Rodriguez, M., Nolan, C. C., Mukherjee, A., Martin, S., Caldas, C., Ellis, I. O., Green, A. R., & Rakha, E. A. (in press). Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion. Modern Pathology, https://doi.org/10.1038/s41379-018-0092-9

Lymphovascular invasion is strongly related to breast cancer metastasis. However, the underlying mechanisms of lymphovascular invasion and its driver molecules in breast cancer remain to be defined. In this study, we explore differential expression o... Read More about Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion.

Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance (2018)
Journal Article
Althobiti, M., Aleskandarany, M. A., Joseph, C., Toss, M., Mongan, N., Diez-Rodriguez, M., Nolan, C. C., Ashankyty, I., Ellis, I. O., Green, A. R., & Rakha, E. A. (2018). Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance. Histopathology, 73(6), 887-896. https://doi.org/10.1111/his.13695

Background: Tumour-infiltrating lymphocytes (TILs) in breast cancer (BC) confer prognostic and predictive information. This study aims to assess the spatial and temporal heterogeneity of TILs in BC and its relationship with immune cell subtypes.
Met... Read More about Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance.

Inhibition of her2 increases jagged1-dependent breast cancer stem cells: Role for membrane jagged1 (2018)
Journal Article
Shah, D., Wyatt, D., Baker, A., Simms, P., Peiffer, D. S., Fernandez, M. L., …Osipo, C. (2018). Inhibition of her2 increases jagged1-dependent breast cancer stem cells: Role for membrane jagged1. Clinical Cancer Research, 24(18), 4566-4578. https://doi.org/10.1158/1078-0432.CCR-17-1952

© 2018 American Association for Cancer Research. Purpose: HER2-positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as cancer stem cells (CSC). CSCs are implicated in radiotherapy... Read More about Inhibition of her2 increases jagged1-dependent breast cancer stem cells: Role for membrane jagged1.

Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort (2018)
Journal Article
Lozada, J. R., Basili, T., Pareja, F., Alemar, B., Paula, A. D. C., Gularte-Merida, R., …Geyer, F. C. (2018). Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort. Histopathology, 73(2), 339-344. https://doi.org/10.1111/his.13522

Aims: Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (BPTC), also known as solid papillary carcinomawith reverse polarity, is a rare histological type of breast cancer that resembles morphologically t... Read More about Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort.

Panoptic overview of triple-negative breast cancer in Nigeria: current challenges and promising global initiatives (2018)
Journal Article
Wright, N., Rida, P., Rakha, E., Agboola, A., & Aneja, R. (2018). Panoptic overview of triple-negative breast cancer in Nigeria: current challenges and promising global initiatives. Journal of Global Oncology, 1-20. https://doi.org/10.1200/jgo.17.00116

Purpose

Triple-negative breast cancer (TNBC) is the most deadly form of breast cancer (BC) today. TNBC treatment is fraught with challenges because of the extensive interpatient heterogeneity in clinical behavior and scarcity of stratifying biomar... Read More about Panoptic overview of triple-negative breast cancer in Nigeria: current challenges and promising global initiatives.

Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas (2018)
Journal Article
Geyer, F. C., Li, A., Papanastasiou, A. D., Smith, A., Selenica, P., Burke, K. A., Edelweiss, M., Wen, H.-C., Piscuoglio, S., Schultheis, A. M., Martelotto, L. G., Pareja, F., Brandes, A., Lozada, J., Macedo, G. S., de Filippo, M. R., Jungbluth, A. A., Foschini, M. P., Wen, H. Y., Brogi, E., …Reis-Filho, J. S. (2018). Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas. Nature Communications, 9, Article 1816. https://doi.org/10.1038/s41467-018-04128-5

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of adenomyoepitheliomas. Massivel... Read More about Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas.

Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients (2018)
Journal Article
Martin, S. G., Lebot, M. N., Sukkarn, B., Ball, G., Green, A. R., Rakha, E. A., …Storr, S. J. (2018). Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients. Oncotarget, 9(40), 25946-25956. https://doi.org/10.18632/oncotarget.25408

G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) i... Read More about Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients.

Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape (2018)
Journal Article
Kader, T., Hill, P., Rakha, E. A., Campbell, I. G., & Gorringe, K. L. (2018). Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape. Breast Cancer Research, 20, 1-11. https://doi.org/10.1186/s13058-018-0967-1

Background
Atypical ductal hyperplasia (ADH) is a common diagnosis in the mammographic era and a significant clinical problem with wide variation in diagnosis and treatment. After a diagnosis of ADH on biopsy a proportion are upgraded to carcinoma u... Read More about Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape.

Tumour heterogeneity of breast cancer: from morphology to personalised medicine (2018)
Journal Article
Aleskandarany, M. A., Vandenberghe, M. E., Marchiò, C., Ellis, I. O., Sapino, A., & Rakha, E. A. (2018). Tumour heterogeneity of breast cancer: from morphology to personalised medicine. Pathobiology, 85(1-2), 23-34. https://doi.org/10.1159/000477851

Breast cancer (BC) displays striking clinical, morphological, and behavioural diversity within a single tumour and between tumours. Currently, mounting evidence indicates that the morphological heterogeneity of BC reflects an underlying spectrum of g... Read More about Tumour heterogeneity of breast cancer: from morphology to personalised medicine.

Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis (2018)
Journal Article
Kurozumi, S., Joseph, C., Sonbul, S., Gorringe, K. L., Pigera, M., Aleskandarany, M. A., Diez-Rodriguez, M., Nolan, C. C., Fujii, T., Shirabe, K., Kuwano, H., Storr, S., Martin, S. G., Ellis, I. O., Green, A. R., & Rakha, E. A. (in press). Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis. Breast Cancer Research and Treatment, 170(3), https://doi.org/10.1007/s10549-018-4777-z

Background: The functions of many proteins are tightly regulated with a complex array of cellular functions including ubiquitination. In cancer cells, aberrant ubiquitination may promote the activity of oncogenic pathways with subsequent tumour progr... Read More about Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis.

Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer (2018)
Journal Article
Alfarsi, L., Johnston, S., Liu, D.-X., Rakha, E., & Green, A. (in press). Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer. Histopathology, https://doi.org/10.1111/his.13523

Endocrine therapy for oestrogen receptor‐positive (ER+) breast cancer (BC) is arguably the most successful targeted cancer therapy to date. Nevertheless, resistance to endocrine therapy still occurs in a significant proportion of patients, limiting i... Read More about Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer.