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DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers (2015)
Journal Article
Abdel-Fatah, T. M., Arora, A., Moseley, P. M., Perry, C., Rakha, E. A., Green, A. R., …Madhusudan, S. (2015). DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers. Oncotarget, 6(26), 21964-21978. https://doi.org/10.18632/oncotarget.4157

Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β,... Read More about DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents (2015)
Journal Article
Ong, C. C., Gierke, S., Pitt, C., Sagolla, M., Cheng, C. K., Zhou, W., …Hoeflich, K. P. (2015). Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Research, 17(1), Article 59. https://doi.org/10.1186/s13058-015-0564-5

Introduction Breast cancer, the most common cause of cancer-related deaths worldwide among women, is a molecularly and clinically heterogeneous disease. Extensive genetic and epigenetic profiling of breast tumors has recently revealed novel puta... Read More about Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents.

FKBPL: a marker of good prognosis in breast cancer (2015)
Journal Article
Nelson, L., McKeen, H. D., Ellis, I., Rakha, E., Marshall, A., Mulrane, L., …Robson, T. (2015). FKBPL: a marker of good prognosis in breast cancer. Oncotarget, 6(14), 12209-12223. https://doi.org/10.18632/oncotarget.3528

FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL’s prognostic ability in primary breast... Read More about FKBPL: a marker of good prognosis in breast cancer.

Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer (2015)
Journal Article
Abduljabbar, R., Negm, O. H., Lai, C., Jerjees, D. A., Al-Kaabi, M., Hamed, M. R., …Ellis, I. O. (2015). Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer. Breast Cancer Research and Treatment, 150(2), 335-346. https://doi.org/10.1007/s10549-015-3335-1

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels... Read More about Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches (2015)
Journal Article
Pinder, S. E., Rakha, E. A., Purdie, C. A., Bartlett, J. M. S., Francis, A., Stein, R. C., …the Translational Subgroup of the NCRI Breast Clinical Studies Group. (2015). Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches. Histopathology, 67(3), 279-293. https://doi.org/10.1111/his.12649

Neoadjuvant chemotherapy (NACT) is used increasingly in the treatment of invasive breast cancer and presents challenges for the pathologist in the handling and interpretation of tissues. Potential issues include pathological identification and locali... Read More about Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches.

The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways (2015)
Journal Article
Jerjees, D. A., Negm, O. H., Alabdullah, M. L., Mirza, S., Alkaabi, M., Hameed, M. R., …Rakha, E. A. (2015). The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways. Breast Cancer Research and Treatment, 150(1), 91-103. https://doi.org/10.1007/s10549-015-3308-4

The mammalian target of rapamycin complex 1 (mTORC1) is a downstream of the PI3K/Akt pathway which affects cancer development. mTORC1 has many downstream signalling effectors that can enhance different cellular responses. This study aims to investiga... Read More about The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways.

DNA damage response markers are differentially expressed in BRCA-mutated breast cancers (2015)
Journal Article
Aleskandarany, M., Caracappa, D., Nolan, C. C., Macmillan, R. D., Ellis, I. O., Rakha, E. A., & Green, A. R. (2015). DNA damage response markers are differentially expressed in BRCA-mutated breast cancers. Breast Cancer Research and Treatment, 150(1), 81-90. https://doi.org/10.1007/s10549-015-3306-6

Cells have stringent DNA repair pathways that are specific for each different set of DNA lesions which is accomplished through the integration of complex array of proteins. However, BRCA-mutated breast cancer (BC) has defective DNA repair mechanisms.... Read More about DNA damage response markers are differentially expressed in BRCA-mutated breast cancers.

Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response (2015)
Journal Article
Al-kaabi, M., Alshareeda, A., Jerjees, D., Muftah, A., Green, A., Alsubhi, N., …Rakha, E. (2015). Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response. British Journal of Cancer, 112(5), 901-911. https://doi.org/10.1038/bjc.2014.576

Background: Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicop... Read More about Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.

Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer (2015)
Journal Article
Arora, A., Abdel-Fatah, T., Agarwal, D., Doherty, R., Moseley, P. M., Aleskandarany, M. A., …Madhusudan, S. (2015). Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer. Molecular Cancer Therapeutics, 14(4), https://doi.org/10.1158/1535-7163.MCT-14-0939

Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition... Read More about Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer.

Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer (2014)
Journal Article
Davis, J., Martin, S. G., Patel, P. M., Green, A. R., Rakha, E. A., Ellis, I. O., & Storr, S. J. (2014). Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer. BMC Cancer, 14(1), https://doi.org/10.1186/1471-2407-14-995

Background The calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been asso... Read More about Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer.

High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity (2014)
Journal Article
Rakha, E. A., Varga, Z., Elsheik, S., & Ellis, I. O. (2015). High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity. Histopathology, 66(5), 740-746. doi:10.1111/his.12591

Aims Encapsulated papillary carcinoma (EPC) is a recognized special type of breast carcinoma. Despite compelling evidence indicating its invasive nature, although not of a conventional form, the current consensus is to manage EPC as an in?situ disea... Read More about High-grade encapsulated papillary carcinoma of the breast: an under-recognized entity.

Biological and clinical significance of PARP1 protein expression in breast cancer (2014)
Journal Article
Green, A. R., Caracappa, D., Benhasouna, A. A., Alshareeda, A., Nolan, C. C., Macmillan, R. D., …Rakha, E. A. (2015). Biological and clinical significance of PARP1 protein expression in breast cancer. Breast Cancer Research and Treatment, 149(2), 353-362. https://doi.org/10.1007/s10549-014-3230-1

Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinic... Read More about Biological and clinical significance of PARP1 protein expression in breast cancer.

Updated UK recommendations for HER2 assessment in breast cancer (2014)
Journal Article
Rakha, E. A., Pinder, S. E., Bartlett, J. M., Ibrahim, M., Starczynski, J., Carder, P. J., …Ellis, I. O. (2015). Updated UK recommendations for HER2 assessment in breast cancer. Journal of Clinical Pathology, 68(2), 93-99. https://doi.org/10.1136/jclinpath-2014-202571

Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies... Read More about Updated UK recommendations for HER2 assessment in breast cancer.

Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer (2014)
Journal Article
Wishart, G. C., Rakha, E., Green, A., Ellis, I., Ali, H. R., Provenzano, E., …Pharoah, P. D. (2014). Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer. BMC Cancer, 14(1), Article 908. https://doi.org/10.1186/1471-2407-14-908

Background PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performa... Read More about Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study (2014)
Journal Article
Rakha, E. A., Tan, P. H., Varga, Z., Tse, G. M., Shaaban, A. M., Climent, F., …Chan, T. (2015). Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study. British Journal of Cancer, 112(2), 283-289. https://doi.org/10.1038/bjc.2014.592

Background: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that has basal-like characteristics and is perceived to have poorer prognosis when compared with conventional no specific type/ductal carcinomas (ductal/NST). However, cu... Read More about Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study.

Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts (2014)
Journal Article
Abdel-Fatah, T. M., Arora, A., Alsubhi, N., Agarwal, D., Moseley, P. M., Perry, C., …Madhusudan, S. (2014). Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts. Neoplasia, 16(11), 982-991. https://doi.org/10.1016/j.neo.2014.09.009

ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression w... Read More about Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts.

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer (2014)
Journal Article
Abdel-Fatah, T. M., Middleton, F. K., Arora, A., Agarwal, D., Chen, T., Moseley, P. M., …Madhusudan, S. (2015). Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer. Molecular Oncology, 9(3), 569-585. https://doi.org/10.1016/j.molonc.2014.10.013

ATR?CHEK1 signalling is critical for genomic stability. ATR?CHEK1 signalling may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. We investigated ATR, CHEK1 and phosphorylated CHEK1 Ser345 protein (pCHEK1)... Read More about Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer.

Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy (2014)
Journal Article
Zhang, Y., Storr, S. J., Johnson, K., Green, A. R., Rakha, E. A., Ellis, I. O., …Martin, S. G. (2014). Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy. Oncotarget, 5(24), https://doi.org/10.18632/oncotarget.2683

Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated b... Read More about Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.