RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer (2023)
Journal Article
Ciscar, M., Trinidad, E. M., Perez-Chacon, G., Alsaleem, M., Jimenez, M., Jimenez-Santos, M. J., …Gonzalez-Suarez, E. (2023). RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer. EMBO Molecular Medicine, Article e16715. https://doi.org/10.15252/emmm.202216715

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein ex... Read More about RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.

Expression, assessment and significance of Ki67 expression in breast cancer: an update (2023)
Journal Article
Lashen, A. G., Toss, M. S., Ghannam, S. F., Makhlouf, S., Green, A., Mongan, N. P., & Rakha, E. (2023). Expression, assessment and significance of Ki67 expression in breast cancer: an update. Journal of Clinical Pathology, Article jcp-2022-208731. https://doi.org/10.1136/jcp-2022-208731

Ki67 expression is one of the most important and cost-effective surrogate markers to assess for tumour cell proliferation in breast cancer (BC). The Ki67 labelling index has prognostic and predictive value in patients with early-stage BC, particularl... Read More about Expression, assessment and significance of Ki67 expression in breast cancer: an update.

Combined proliferation and apoptosis index provides better risk stratification in breast cancer (2023)
Journal Article
Ibrahim, A., Toss, M. S., Atallah, N. M., Al Saleem, M., Green, A. R., & Rakha, E. (2023). Combined proliferation and apoptosis index provides better risk stratification in breast cancer. Histopathology, https://doi.org/10.1111/his.14887

Introduction Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and a... Read More about Combined proliferation and apoptosis index provides better risk stratification in breast cancer.

High inner centromere protein (INCENP) expression correlates with aggressive features and predicts poor prognosis in patients with invasive breast cancer (2023)
Journal Article
Ibrahim, A., Miligy, I. M., Toss, M. S., Green, A. R., & Rakha, E. A. (in press). High inner centromere protein (INCENP) expression correlates with aggressive features and predicts poor prognosis in patients with invasive breast cancer. Pathobiology,

Introduction: Inner centromere protein (INCENP) is a member of the chromosomal passenger complex (CPC) and plays a key role in mitosis and cell proliferation. This study aims to evaluate the clinical and prognostic significance of INCENP in invasive... Read More about High inner centromere protein (INCENP) expression correlates with aggressive features and predicts poor prognosis in patients with invasive breast cancer.

The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up (2023)
Journal Article
Lashen, A. G., Toss, M. S., Mongan, N. P., Green, A. R., & Rakha, E. A. (2023). The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up. Cancer, 129(8), 1183-1194. https://doi.org/10.1002/cncr.34655

Background: The routine assessment of progesterone receptor (PR) expression in breast cancer (BC) remains controversial. This study aimed to evaluate the role of PR expression in luminal BC, with emphasis on the definition of positivity and its progn... Read More about The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up.

The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development (2022)
Journal Article
Aljohani, A. I., Toss, M. S., Green, A. R., & Rakha, E. (2022). The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development. Breast Cancer Research and Treatment, https://doi.org/10.1007/s10549-022-06801-2

Background Lymphovascular invasion (LVI) is regulated through complex molecular mechanisms. Cyclin B1 (CCNB1) was previously determined as being associated with LVI using large cohorts of breast cancer (BC) and artificial neural network (ANN) techni... Read More about The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development.

A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients (2022)
Journal Article
Xu, Q., Kaur, J., Wylie, D., Mittal, K., Li, H., Kolachina, R., …Aneja, R. (2022). A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients. International Journal of Molecular Sciences, 23(21), Article 13322. https://doi.org/10.3390/ijms232113322

Extensive intratumoral heterogeneity (ITH) is believed to contribute to therapeutic failure and tumor recurrence, as treatment-resistant cell clones can survive and expand. However, little is known about ITH in triple-negative breast cancer (TNBC) be... Read More about A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients.

Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods (2022)
Journal Article
Lashen, A., Toss, M. S., Green, A. R., Mongan, N. P., & Rakha, E. (2022). Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods. Histopathology, 81(6), 786-798. https://doi.org/10.1111/his.14781

Background: Ki67 reflects the proliferation activity in breast cancer (BC). However, an optimal method for its assessment in clinical settings has yet to be robustly defined. In this study, we compared several methods to score Ki67 to identify a reli... Read More about Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods.

Refining the definition of HER2-low class in invasive breast cancer (2022)
Journal Article
Atallah, N. M., Toss, M. S., Green, A. R., Mongan, N. P., Ball, G., & Rakha, E. A. (2022). Refining the definition of HER2-low class in invasive breast cancer. Histopathology, 81(6), 770-785. https://doi.org/10.1111/his.14780

Background: Emerging evidence indicates that breast cancer (BC) patients whose tumours express HER2 protein without HER2 gene amplification (HER2-low), can benefit from antibody–drug conjugates (ADC). However, the current definition of HER2-low BC re... Read More about Refining the definition of HER2-low class in invasive breast cancer.

Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ (2022)
Journal Article
Miligy, I. M., Toss, M. S., Gorringe, K. L., Ellis, I. O., Green, A. R., & Rakha, E. A. (2022). Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ. Pathobiology, 89(6), 382–392. https://doi.org/10.1159/000522244

Aurora Kinase A (AURKA/STK15) has a role in centrosome duplication and is a regulator of mitotic cell proliferation. It is over-expressed in breast cancer and other cancers, however; its role in ductal carcinoma in situ (DCIS) remains to be defined.... Read More about Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ.

Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer (2022)
Journal Article
Saunus, J. M., De Luca, X. M., Northwood, K., Raghavendra, A., Hasson, A., McCart Reed, A. E., …Lakhani, S. R. (2022). Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer. npj Breast Cancer, 8(1), Article 57. https://doi.org/10.1038/s41523-022-00425-x

Intratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We... Read More about Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer.

The characteristics and clinical significance of atypical mitosis in breast cancer (2022)
Journal Article
Lashen, A., Toss, M. S., Alsaleem, M., Green, A. R., Mongan, N. P., & Rakha, E. (2022). The characteristics and clinical significance of atypical mitosis in breast cancer. Modern Pathology, 35, 1341-1348. https://doi.org/10.1038/s41379-022-01080-0

Atypical mitosis is considered a feature of malignancy, however, its significance in breast cancer (BC) remains elusive. Here, we aimed to assess the clinical value of atypical mitoses in BC and to explore their underlying molecular features. Atypica... Read More about The characteristics and clinical significance of atypical mitosis in breast cancer.

Standardization of the tumor-stroma ratio scoring method for breast cancer research (2022)
Journal Article
Hagenaars, S. C., Vangangelt, K. M. H., Van Pelt, G. W., Karancsi, Z., Tollenaar, R. A. E. M., Green, A. R., …Mesker, W. E. (2022). Standardization of the tumor-stroma ratio scoring method for breast cancer research. Breast Cancer Research and Treatment, 193, 545-553. https://doi.org/10.1007/s10549-022-06587-3

Purpose: The tumor-stroma ratio (TSR) has repeatedly proven to be correlated with patient outcomes in breast cancer using large retrospective cohorts. However, studies validating the TSR often show variability in methodology, thereby hampering compar... Read More about Standardization of the tumor-stroma ratio scoring method for breast cancer research.

Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion (2022)
Journal Article
Aljohani, A. I., Toss, M. S., El-Sharawy, K. A., Mirza, S., Ball, G. R., Green, A. R., & Rakha, E. (2022). Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion. American Journal of Cancer Research, 12(2), 469-489

Lymphovascular invasion (LVI) is a key step in breast cancer (BC) metastasis. Targeting the molecular drivers of LVI can improve BC patients’ management. However, the underlying molecular mechanisms of LVI are complex and interconnected with various... Read More about Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion.

Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer (2022)
Journal Article
Kariri, Y., Toss, M. S., Alsaleem, M., Elsharawy, K. A., Joseph, C., Mongan, N. P., …Rakha, E. A. (2022). Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer. Breast Cancer Research and Treatment, 192(3), 529-539. https://doi.org/10.1007/s10549-022-06531-5

Background The Ubiquitin-conjugating enzyme 2C (UBE2C) is essential for the ubiquitin–proteasome system and is involved in cancer cell migration and apoptosis. This study aimed to determine the prognostic value of UBE2C in invasive breast cancer (BC... Read More about Ubiquitin-conjugating enzyme 2C (UBE2C) is a poor prognostic biomarker in invasive breast cancer.

Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer (2021)
Journal Article
Althobiti, M., El-Sharawy, K. A., Joseph, C., Aleskandarany, M., Toss, M. S., Green, A. R., & Rakha, E. A. (2021). Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer. Breast Cancer Research and Treatment, 189(3), 621-630. https://doi.org/10.1007/s10549-021-06336-y

Purpose The outcome of the luminal oestrogen receptor-positive (ER +) subtype of breast cancer (BC) is highly variable and patient stratification needs to be refined. We assessed the prognostic significance of oestrogen-regulated solute carrier fami... Read More about Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer.

The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS) (2021)
Journal Article
Al-Kawaz, A., Ali, R., Toss, M. S., Miligy, I. M., Mohammed, O. J., Green, A. R., …Rakha, E. A. (2021). The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS). Breast Cancer Research and Treatment, 190, 39-51. https://doi.org/10.1007/s10549-021-06357-7

Background: The prediction of clinical behaviour of breast ductal carcinoma in situ (DCIS) and its progression to invasive disease remains a challenge. Alterations of DNA damage repair mechanisms are associated with invasive breast cancer (BC). This... Read More about The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS).

The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer (2021)
Journal Article
Masisi, B. K., El Ansari, R., Alfarsi, L., Craze, M. L., Jewa, N., Oldfield, A., …Green, A. R. (2021). The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer. Cancers, 13(16), Article 3963. https://doi.org/10.3390/cancers13163963

Glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assess... Read More about The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer.

SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in oestrogen receptor-positive breast cancer (2021)
Journal Article
Alfarsi, L. H., Ansari, R. E., Craze, M. L., Mohammed, O. J., Masisi, B. K., Ellis, I. O., …Green, A. R. (2021). SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in oestrogen receptor-positive breast cancer. Breast Cancer Research and Treatment, 189(2), 317-331. https://doi.org/10.1007/s10549-021-06298-1

Purpose: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The... Read More about SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in oestrogen receptor-positive breast cancer.

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ (2021)
Journal Article
Al-Kawaz, A., Miligy, I. M., Toss, M. S., Mohammed, O. J., Green, A. R., Madhusudan, S., & Rakha, E. A. (2021). The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ. Breast Cancer Research and Treatment, 188(1), 53-63. https://doi.org/10.1007/s10549-021-06271-y

Background Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast c... Read More about The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ.