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Cell division cycle 6 (CDC6) is an independent prognostic biomarker in breast cancer (2024)
Journal Article
Kariri, Y. A., Alsaleem, M., Alhatlani, B. Y., Al-Kawaz, A., Mongan, N. P., Green, A. R., & Rakha, E. A. (2024). Cell division cycle 6 (CDC6) is an independent prognostic biomarker in breast cancer. Pathology, https://doi.org/10.1016/j.pathol.2024.09.006

Cell division cycle 6 (CDC6) is a cell cycle protein involved in cell cycle control, DNA replication and cancer cell apoptosis. This study investigated the prognostic value of CDC6 in breast cancer (BC) utilising large well characterised cohorts of e... Read More about Cell division cycle 6 (CDC6) is an independent prognostic biomarker in breast cancer.

Cell cycle traverse rate predicts long-term outcomes in a multi-institutional cohort of patients with triple-negative breast cancer (2024)
Journal Article
Bhattarai, S., Rupji, M., Chao, H.-P., Xu, Q., Saini, G., Rida, P., Aleskandarany, M. A., Green, A. R., Ellis, I. O., Janssen, E. A., Jonsdottir, K., Rakha, E., Kowalski-Mueggen, J., & Aneja, R. (2024). Cell cycle traverse rate predicts long-term outcomes in a multi-institutional cohort of patients with triple-negative breast cancer. BJC Reports, 2(1), Article 87. https://doi.org/10.1038/s44276-024-00097-z

Background
Ki67 index (KI) and mitotic index (MI) are proliferation markers with established prognostic value in breast carcinomas. While KI is evaluated immunohistochemically and reported as a percentage, MI is determined visually and reflects tota... Read More about Cell cycle traverse rate predicts long-term outcomes in a multi-institutional cohort of patients with triple-negative breast cancer.

Hydroxyacid Oxidase 1, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Luminal Breast Cancer (2024)
Journal Article
Erkan, B., MacIntyre, S., Brown, C., Fakroun, A., Lashen, A. G., Mongan, N. P., Ellis, I. O., Rakha, E. A., & Green, A. R. (2024). Hydroxyacid Oxidase 1, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Luminal Breast Cancer. International Journal of Molecular Sciences, 25(21), Article 11572. https://doi.org/10.3390/ijms252111572

Breast cancer (BC), which remains the most prevalent malignancy among women, is characterised by significant heterogeneity across its molecular subtypes. Oestrogen receptor-positive (ER+) (luminal) BC represents approximately 75% of cases, and despit... Read More about Hydroxyacid Oxidase 1, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Luminal Breast Cancer.

Prognostic and clinical significance of the proliferation marker MCM7 in breast cancer (2024)
Journal Article
Lashen, A. G., Toss, M. S., Rutland, C. S., Green, A. R., Mongan, N. P., & Rakha, E. (2024). Prognostic and clinical significance of the proliferation marker MCM7 in breast cancer. Pathobiology, https://doi.org/10.1159/000540790

Introduction: Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined.... Read More about Prognostic and clinical significance of the proliferation marker MCM7 in breast cancer.

Stromal lymphocytes are associated with upgrade of B3 breast lesions (2024)
Journal Article
Kader, T., Provenzano, E., Jayawardana, M. W., Hendry, S., Pang, J.-M., Elder, K., Byrne, D. J., Tjoeka, L., Frazer, H. M., House, E., Jayasinghe, S. I., Keane, H., Murugasu, A., Rajan, N., Miligy, I., Toss, M., Green, A., Rakha, E., Fox, S. B., Mann, B., …Gorringe, K. L. (2024). Stromal lymphocytes are associated with upgrade of B3 breast lesions. Breast Cancer Research, 26, Article 115

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated... Read More about Stromal lymphocytes are associated with upgrade of B3 breast lesions.

Nottingham Prognostic x (NPx): a risk stratification tool in ER-positive HER2-negative breast cancer: A validation study (2024)
Journal Article
Lashen, A. G., Toss, M., Miligy, I., Rewcastle, E., Kiraz, U., Janssen, E. A. M., Green, A. R., Quinn, C., Ellis, I., & Rakha, E. (2024). Nottingham Prognostic x (NPx): a risk stratification tool in ER-positive HER2-negative breast cancer: A validation study. Histopathology, 85(3), 468-477. https://doi.org/10.1111/his.15234

Aims
In this study, we validate the use of Nottingham Prognostic x (NPx), consisting of tumour size, tumour grade, progesterone receptor (PR) and Ki67 in luminal BC.

Materials and methods
Two large cohorts of luminal early-stage BC (n = 2864) we... Read More about Nottingham Prognostic x (NPx): a risk stratification tool in ER-positive HER2-negative breast cancer: A validation study.

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., Ellis, I. O., Rakha, E. 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, 56(6), 826-833. 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.

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., Ellis, I. O., Rakha, E. 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.

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.-L., Geukens, T., Maetens, M., Aparicio, S., Bassez, A., Borg, A., Brock, J., Broeks, A., Caldas, C., Cardoso, F., De Schepper, M., Delorenzi, M., Drukker, C. A., Glas, A. M., Green, A. R., Isnaldi, E., Eyfjörð, J., Khout, H., Knappskog, S., Krishnamurthy, S., …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., Green, A. R., & 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.

High Inner Centromere Protein 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. (2023). High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer. Pathobiology, 90(6), 377–388. https://doi.org/10.1159/000529628

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 Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer.

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., Perez-Montoyo, H., Sanz-Moreno, A., Vethencourt, A., Toss, M., Petit, A., Soler-Monso, M. T., Lopez, V., Gomez-Miragaya, J., Gomez-Aleza, C., Dobrolecki, L. E., Lewis, M. T., Bruna, A., Mouron, S., Quintela-Fandino, M., …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.

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.

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.

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., Aleskandarany, M., Toss, M. S., Green, A. R., Yang, J., Yankeelov, T. E., Bhattarai, S., Janssen, E. A., Kong, J., Rakha, E. A., Kowalski, J., & 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.

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.