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ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer (2024)
Journal Article
Patel, R., Alfarsi, L. H., El-Ansari, R., Masisi, B. K., Erkan, B., Fakroun, A., …Green, A. R. (in press). ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer. Pathobiology, https://doi.org/10.1159/000539564

Purpose: ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated. Methods: ATF4 expre... Read More about ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer.

The characteristics and prognostic significance of histone H1 expression in breast cancer (2024)
Journal Article
Lashen, A. G., Almalki, N., Toss, M., Mirza, S., Malki, M. I., Rutland, C. S., Jeyapalan, J. N., Green, A. R., Mongan, N. P., Madhusudan, S., & Rakha, E. A. (2024). The characteristics and prognostic significance of histone H1 expression in breast cancer. Pathology, https://doi.org/10.1016/j.pathol.2024.03.012

Histone H1 (H.H1) is involved in chromatin organisation and gene regulation and is overexpressed in many malignant tumours, including breast cancer (BC). This study proposed and evaluated the prognostic role of H.H1 expression in BC. H.H1 mRNA exp... Read More about The characteristics and prognostic significance of histone H1 expression in breast cancer.

Tripartite Motif Containing 2, a glutamine metabolism-associated protein, predicts poor patient outcome in triple negative breast cancer treated with chemotherapy (2024)
Journal Article
Masisi, B. K., El Ansari, R., Alfarsi, L., Fakroun, A., Erkan, B., Ibrahim, A., Toss, M., Ellis, I. O., Rakha, E. A., & Green, A. R. (2024). Tripartite Motif Containing 2, a glutamine metabolism-associated protein, predicts poor patient outcome in triple negative breast cancer treated with chemotherapy. Cancers, 16(11), Article 1949. https://doi.org/10.3390/cancers16111949

Background: Breast cancer (BC) remains heterogeneous in terms of prognosis and response to treatment. Metabolic reprogramming is a critical part of oncogenesis and a potential therapeutic target. Glutaminase (GLS), which generates glutamate from glut... Read More about Tripartite Motif Containing 2, a glutamine metabolism-associated protein, predicts poor patient outcome in triple negative breast cancer treated with chemotherapy.

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype (2024)
Journal Article
Makhlouf, S., Atallah, N. M., Polotto, S., Lee, A. H., Green, A. R., & Rakha, E. A. (2024). Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype. Cancers, 16(10), Article 1893. https://doi.org/10.3390/cancers16101893

Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse gro... Read More about Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype.

The amino acid transporter SLC7A11 expression in breast cancer (2023)
Journal Article
Nath, P., Alfarsi, L. H., El-Ansari, R., Masisi, B. K., Erkan, B., Fakroun, A., …Green, A. R. (2024). The amino acid transporter SLC7A11 expression in breast cancer. Cancer Biology and Therapy, 25(1), Article 2291855. https://doi.org/10.1080/15384047.2023.2291855

Breast cancer (BC), characterized by its diverse molecular profiles and clinical outcomes, presents a significant challenge in the development of effective therapeutic strategies. Metabolic reprogramming, a defining characteristic of cancer, has emer... Read More about The amino acid transporter SLC7A11 expression in breast cancer.

Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways (2023)
Journal Article
Saidy, B., Vasan, R., Durant, R., Greener, M., Immanuel, A., Green, A. R., …Storr, S. J. (2023). Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways. Scientific Reports, 13(1), Article 21163. https://doi.org/10.1038/s41598-023-48198-y

DARPP-32 is a key regulator of protein-phosphatase-1 (PP-1) and protein kinase A (PKA), with its function dependent upon its phosphorylation state. We previously identified DKK1 and GRB7 as genes with linked expression using Artificial Neural Network... Read More about Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways.

The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion (2023)
Journal Article
Aljohani, A., Alsaeed, S., Toss, M., Raafat, S., GREEN, A., & Rakha, E. (2023). The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion. American Journal of Cancer Research, 13(11), 5334–5351

Lymphovascular invasion (LVI) is a common phenomenon in breast cancer (BC), and it is correlated to poor outcome. However, the biomarkers that influence the development of LVI remain to be defined. Through rigorous bioinformatics analyses, high mobil... Read More about The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion.

Obesity-associated changes in molecular biology of primary breast cancer (2023)
Journal Article
Nguyen, H., Geukens, T., Maetens, M., Aparicio, S., Bassez, A., Borg, A., …Desmedt, C. (2023). Obesity-associated changes in molecular biology of primary breast cancer. Nature Communications, 14, Article 4418. https://doi.org/10.1038/s41467-023-39996-z

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs acc... Read More about Obesity-associated changes in molecular biology of primary breast cancer.

The clinical and biological significance of estrogen receptor-low positive breast cancer (2023)
Journal Article
Makhlouf, S., Althobi, M., Toss, M., Muftah, A. A., Mongan, N. P., Lee, A. H. S., …Rakha, E. A. (2023). The clinical and biological significance of estrogen receptor-low positive breast cancer. Modern Pathology, 36(10), Article 100284. https://doi.org/10.1016/j.modpat.2023.100284

Estrogen Receptor (ER) status in breast cancer (BC) is determined using immunohistochemistry (IHC) with nuclear expression in ≥1% of cells defined as ER-positive. BC with 1-9% expression (ER-low positive), is a clinically and biologically unique subg... Read More about The clinical and biological significance of estrogen receptor-low positive breast cancer.

Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival (2023)
Journal Article
Kalvala, J., Parks, R. M., Abdi, J., Green, A. R., & Cheung, K. L. (2023). Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival. Advances in Therapy, https://doi.org/10.1007/s12325-023-02504-2

Introduction Breast cancer in older women tends to have more favourable biology, compared to younger women. Androgen receptor (AR) is significant for breast tumour carcinogenesis; however, the role of AR in older women has not been fully explored.... Read More about Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival.

A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease (2023)
Journal Article
Storr, S. J., Hoskin, V., Aiyappa‐Maudsley, R., Ghaffari, A., Varma, S., Green, A., …Martin, S. G. (2023). A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease. Cancer Medicine, 12(9), 10908-10916. https://doi.org/10.1002/cam4.5802

Introduction: The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to da... Read More about A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease.

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, 15(4), 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, 76(6), Article 357-364. 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.

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.

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.

Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer (2022)
Journal Article
Kariri, Y. A., Joseph, C., Alsaleem, M. A., Elsharawy, K. A., Alsaeed, S., Toss, M. S., …Rakha, E. A. (2022). Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer. Cancers, 14(22), Article 5643. https://doi.org/10.3390/cancers14225643

Background: Cell Division Cycle Associated 5 (CDCA5) plays a role in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling pathway involving cell division, cancer cell migration and apoptosis. This study aims to assess the prognostic and biologica... Read More about Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer.

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.

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.

Breast tumor microenvironment structures are associated with genomic features and clinical outcome (2022)
Journal Article
Danenberg, E., Bardwell, H., Zanotelli, V. R. T., Provenzano, E., Chin, S. F., Rueda, O. M., …Ali, H. R. (2022). Breast tumor microenvironment structures are associated with genomic features and clinical outcome. Nature Genetics, 54, 660–669. https://doi.org/10.1038/s41588-022-01041-y

The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in... Read More about Breast tumor microenvironment structures are associated with genomic features and clinical outcome.

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.