Review
Endocrinology & Metabolism
Tara Hyder, Christopher C. Marino, Sasha Ahmad, Azadeh Nasrazadani, Adam M. Brufsky
Summary: Aromatase inhibitors (AIs) are essential in the management of hormone receptor-positive (HR+) breast cancer, but their use is limited by the musculoskeletal adverse effects known as aromatase inhibitor-associated musculoskeletal syndrome (AIMSS), which includes bone loss and arthralgias. The pathophysiology of AIMSS is not fully understood, but is proposed to be related to estrogen deprivation in the musculoskeletal and nervous systems.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Oncology
Manuela Rabaglio, Zhuoxin Sun, Rudolf Maibach, Anita Giobbie-Hurder, Bent Ejlertsen, Vernon J. Harvey, Patrick Neven, Istvan Lang, Herve Bonnefoi, Andrew Wardley, Barbara Ruepp, Monica Castiglione, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Marco Colleoni, Beat Thurlimann, Meredith M. Regan
Summary: This study investigates cardiovascular events in breast cancer patients during treatment with different drugs and found that monotherapy with letrozole is associated with a higher risk of ischemic heart disease, while the use of tamoxifen increases the risk of thromboembolic events.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Review
Medicine, Research & Experimental
Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Dhanushya Nagarajan, K. K. Vibhaa, V Anagha, P. Joshua Paul, T. Tharani Priya, Rituraj Chakraborty, Kaviyarasi Renu, Abhijit Dey, Balachandar Vellingiri, Abilash Valsala Gopalakrishnan
Summary: The highly active estrogen metabolism and receptor protein expression contribute to the elevated breast cancer rate in post-menopausal women. Letrozole, an aromatase inhibitor, is an effective endocrine medication used in the treatment of breast cancer. It can also stimulate ovulation in infertile pre-menopausal women. However, its potential benefits in fertility treatments have not been fully utilized.
Article
Medicine, General & Internal
Adhari AlZaabi, Hafsa AlAmri, Ghadeer ALAjmi, Manhal Allawati, Fatema Muhanna, Ruqaia Alabri, Fatema AlBusaidi, Shaima AlGhafri, Abdulrahman A. Al-Mirza, Khalid Al Baimani
Summary: The study assessed the risk of endometrial pathologies in female breast cancer patients treated with tamoxifen and aromatase inhibitors at Sultan Qaboos University Hospital in Oman. The results showed that premenopausal patients did not have an increased risk of endometrial cancer with tamoxifen and letrozole treatment. Breast cancer patients on these medications may need pre-treatment endometrial evaluation and explanation of alarming symptoms to guide further surveillance.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Review
Oncology
Leanne Fleming, Sommer Agnew, Nicola Peddie, Megan Crawford, Diane Dixon, Iain MacPherson
Summary: This study aims to analyze the impact of side effects of hormone therapy (HT) on adherence and persistence behaviors. Sixty-two eligible research papers were identified through electronic searches, and a lack of consistency in the measurement of adherence and the definition of persistence was found. The instruments used to measure side effects also varied significantly. These variations and lack of consistency make it difficult to evaluate and summarize the role of HT side effects in adherence and persistence behavior.
Article
Obstetrics & Gynecology
Liv C. Poulsen, Agnieszka K. Warzecha, Nathalie S. Bulow, Leif Bungum, Nicholas S. Macklon, Claus Yding Andersen, Sven O. Skouby
Summary: The study demonstrates that letrozole cotreatment has significant effects on follicle diameter and corpus luteum function during ovarian stimulation, without impacting the recruitment of secondary follicles.
HUMAN REPRODUCTION
(2022)
Review
Oncology
Nicola Peddie, Sommer Agnew, Megan Crawford, Diane Dixon, Iain MacPherson, Leanne Fleming
Summary: Research indicates that the side effects experienced by breast cancer survivors undergoing hormone therapy significantly impact their quality of life. Lack of support from healthcare providers often leads survivors to employ self-management strategies, resulting in non-adherence and non-persistence behaviors.
Article
Obstetrics & Gynecology
Erika P. New, Samantha Kodama, Kate Devine, Samad Jahandideh, Anthony N. Imudia, Shayne M. Plosker
Summary: This retrospective cohort study aimed to determine the association between serum estradiol (E2) level at the time of hCG trigger or LH surge and the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI). The results showed that patients with higher E2 levels had higher LBR and clinical pregnancy rates in letrozole OI cycles followed by IUI. Therefore, it is recommended to delay hCG trigger until the E2 level reaches the physiological periovulatory level to improve pregnancy rates with letrozole followed by IUI.
FERTILITY AND STERILITY
(2023)
Article
Oncology
Jooyoung Oh, Hye Sun Lee, Soyoung Jeon, Dooreh Kim, Jeong-Ho Seok, Woo-Chan Park, Jae-Jin Kim, Chang Ik Yoon
Summary: This study, using a nationwide population-based cohort, found no evidence that endocrine treatment increases the risk of depression in breast cancer patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Behavioral Sciences
Melise Edwards, Sam Lam, Ravi Ranjan, Mariana Pereira, Courtney Babbitt, Agnes Lacreuse
Summary: Aromatase inhibitors (AIs) are commonly used drugs for treating estrogen receptor (ER)-dependent breast cancers, but they can cause adverse effects. Previous studies in marmosets have shown that AIs can replicate these negative effects and increase estradiol levels in the hippocampus. RNA-sequencing analysis revealed that AIs may differentially affect males and females, potentially through processes mediated by the CYP450 superfamily.
HORMONES AND BEHAVIOR
(2023)
Review
Obstetrics & Gynecology
Zhuo Liu, Yuli Geng, Yanjing Huang, Runan Hu, Fan Li, Yufan Song, Mingmin Zhang
Summary: The study aimed to evaluate the effect of letrozole and clomiphene citrate on women with infertility and polycystic ovarian syndrome (PCOS). A total of 29 randomized controlled trials (RCTs) were included, involving 3,952 women and 7,633 ovulation induction cycles. The pooled analysis showed that letrozole had superior outcomes in terms of ovulation rate, clinical pregnancy rate, and live-birth rate compared to clomiphene citrate. Therefore, letrozole is recommended as an ovulation induction drug in women with infertility and PCOS.
OBSTETRICS AND GYNECOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Borja Diaz de Grenu, Diego M. Fernandez-Aroca, Juan A. Organero, Gema Dura, Felix Angel Jalon, Ricardo Sanchez-Prieto, M. Jose Ruiz-Hidalgo, Ana Maria Rodriguez, Lucia Santos, Jose L. Albasanz, Blanca R. Manzano
Summary: Compound 6, a new derivative of aromatase inhibitors, exhibits higher inhibitory activity and potent cytostatic behavior compared to established inhibitors, making it a promising candidate for hormone-dependent cancer treatment.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)
Article
Oncology
Maurice J. Berkowitz, Carlie K. Thompson, Laura T. Zibecchi, Minna K. Lee, Elani Streja, Jacob S. Berkowitz, Cachet M. Wenziger, Jennifer L. Baker, Maggie L. DiNome, Deanna J. Attai
Summary: The survey revealed that many HR+ breast cancer patients experience side effects during ET, with about one-third discontinuing treatment prematurely. While most felt supported by their medical team, 31.5% reported that their side effects were dismissed or minimized.
JOURNAL OF CANCER SURVIVORSHIP
(2021)
Editorial Material
Oncology
Johanna E. Poterala, Kari B. Wisinski
Summary: A shorter course of endocrine therapy may be reasonable for breast cancer patients with low estrogen receptor expression, but further validation is needed.
Article
Cell Biology
Stephanie Stanelle-Bertram, Sebastian Beck, Nancy Kouassi Mounogou, Berfin Schaumburg, Fabian Stoll, Amirah Al Jawazneh, Zoe Schmal, Tian Bai, Martin Zickler, Georg Beythien, Kathrin Becker, Madeleine de la Roi, Fabian Heinrich, Claudia Schulz, Martina Sauter, Susanne Krasemann, Philine Lange, Axel Heinemann, Debby van Riel, Lonneke Leijten, Lisa Bauer, Thierry P. P. van den Bosch, Boaz Lopuhaa, Tobias Busche, Daniel Wibberg, Dirk Schaudien, Torsten Goldmann, Anna Luettohann, Jenny Ruschinski, Hanna Jania, Zacharias Mueller, Vinicius Pinho dos Reis, Vanessa Krupp-Buzimkic, Martin Wolff, Chiara Fallerini, Margherita Baldassarri, Simone Furini, Katrina Norwood, Christopher Kaeufer, Nina Schuetzenmeister, Maren von Koeckritz-Blickwede, Maria Schroeder, Dominik Jarczak, Axel Nierhaus, Tobias Welte, Stefan Kluge, Alice C. Mchardy, Frank Sommer, Joern Kalinowski, Susanne Krauss-Etschmann, Franziska Richter, Jan von der Thuesen, Wolfgang Baumgaertner, Karin Klingel, Benjamin Ondruschka, Alessandra Renieri, Guelsah Gabriel
Summary: The male sex is a major risk factor for severe COVID-19 outcome, but the underlying mechanisms are still unknown. The CYP19A1 gene, encoding the enzyme involved in testosterone-to-estradiol metabolism, has been identified as a host factor contributing to worse disease outcome in SARS-CoV-2-infected males. The study demonstrates increased CYP19A1 expression in the lung tissue and dysregulated sex hormone levels in male hamsters infected with SARS-CoV-2, and treatment with a CYP19A1 inhibitor improves lung function and restores sex hormone balance in males.
CELL REPORTS MEDICINE
(2023)
Article
Cell & Tissue Engineering
Sidse Ehnnsen, Henrik J. Ditzel
Summary: Breast cancer stem cells play a crucial role in cancer initiation, therapy resistance, and progression, with recent research focusing on cellular signaling pathways such as the WNT pathway, NF-κB pathway, and cholesterol biosynthesis pathway. Targeting these pathways in combination with standard treatments may improve the prognosis of breast cancer patients.
Review
Genetics & Heredity
Behzad Mansoori, Ali Mohammadi, Henrik J. Ditzel, Pascal H. G. Duijf, Vahid Khaze, Morten F. Gjerstorff, Behzad Baradaran
Summary: HMGA2 is a DNA architectural protein that regulates gene expression and is highly expressed in embryonic stem cells during development but re-expressed in most human malignancies, where it plays a critical role in promoting tumorigenesis through various mechanisms. HMGA2 increases cancer cell proliferation and resistance to chemotherapy, and influences DNA repair mechanisms and epithelial-to-mesenchymal transition, suggesting its potential as a diagnostic, prognostic, and therapeutic target in cancer.
Letter
Oncology
Sidse Ehmsen, Anders Asmussen, Stefan S. Jeppesen, Anna Christine Nilsson, Sabina Osterlev, Hanne Vestergaard, Ulrik S. Justesen, Isik S. Johansen, Henrik Frederiksen, Henrik J. Ditzel
Article
Oncology
Mikkel G. Terp, Odd L. Gammelgaard, Henriette Vever, Morten F. Gjerstorff, Henrik J. Ditzel
Summary: RAS-MAPK signaling promotes immune evasion and cancer cell survival, and MAPKi can impact the tumor microenvironment indirectly through changes in tumor cells, leading to upregulation of the immunosuppressive protein CD73. Combining anti-CD73 antibodies and MAPKi enhances antitumor effect and alters intratumor immune cell composition significantly.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Ann-Kristine Weber Giger, Helena Mogelbjerg Ditzel, Trine Lembrecht Jorgensen, Henrik Jorn Ditzel, Afsaneh Mohammadnejad, Marianne Ewertz, Per Pfeiffer, Cecilia Margareta Lund, Jesper Ryg
Summary: The study aims to evaluate the effects of Comprehensive Geriatric Assessment (CGA) as an additional intervention in older patients with cancer, with recruitment starting in November 2020 and ongoing. Through a randomized controlled trial, the research will examine the impact of CGA on patients aged 70 and above, diagnosed with cancer and identified as frail.
JOURNAL OF GERIATRIC ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Carla L. Alves, Sidse Ehmsen, Mikkel G. Terp, Neil Portman, Martina Tuttolomondo, Odd L. Gammelgaard, Monique F. Hundebol, Kamila Kaminska, Lene E. Johansen, Martin Bak, Gabriella Honeth, Ana Bosch, Elgene Lim, Henrik J. Ditzel
Summary: The study demonstrates that triple inhibition with fulvestrant, CDK4/6i, and AKT inhibitor durably impairs growth of breast cancer cells, prevents progression, and reduces metastasis. Switching from combined fulvestrant and CDK4/6i to dual combination with AKTi and fulvestrant does not prevent tumor progression after resistance. High phospho-AKT levels in metastasis correlate with shorter progression-free survival in breast cancer patients treated with a combination of CDK4/6i and endocrine therapy.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Simone Johansen, Sofie Traynor, Malene Laage Ebstrup, Mikkel Green Terp, Christina Bog Pedersen, Henrik Jorn Ditzel, Morten Frier Gjerstorff
Summary: The transcription factor ZBED1 is highly expressed in trophoblast cells and may play important roles in placental biology, including maintaining a steady pool of cytotrophoblast cells, regulating trophoblast cell survival and apoptosis, and modulating maternal immune tolerance.
Letter
Oncology
Sidse Ehmsen, Anders Asmussen, Stefan S. Jeppesen, Anna Christine Nilsson, Sabina Osterlev, Amalie Kragh, Henrik Frederiksen, Henrik J. Ditzel
Article
Oncology
Maria L. Lotsberg, Gro V. Rosland, Austin J. Rayford, Sissel E. Dyrstad, Camilla T. Ekanger, Ning Lu, Kirstine Frantz, Linda E. B. Stuhr, Henrik J. Ditzel, Jean Paul Thiery, Lars A. Akslen, James B. Lorens, Agnete S. T. Engelsen
Summary: The lack of adequate preclinical models hinders cancer drug development, and the heterotypic multicellular spheroids offer a promising solution. This study extensively characterizes the spheroids and demonstrates their applicability in evaluating the impact of cancer cell phenotype in drug screening experiments. High-dimensional and spatially resolved imaging mass cytometry analysis provides detailed insights into the heterogeneity of cancer-stroma interactions and epithelial phenotypic plasticity, which are crucial factors in therapy resistance in non-small cell lung cancer (NSCLC).
FRONTIERS IN ONCOLOGY
(2022)
Article
Peripheral Vascular Disease
A. Augusto B. Peluso, Stefan J. Kempf, Thiago Verano-Braga, Lucas Rodrigues-Ribeiro, Lene Egedal Johansen, Mie Rytz Hansen, Gitte Kitlen, Andreas Houe Haugaard, Colin Sumners, Henrik J. Ditzel, Robson A. Santos, Michael Bader, Martin R. Larsen, U. Muscha Steckelings
Summary: This study mapped the changes in the phosphorylation status of human aortic endothelial cells in response to AT(2)-receptor stimulation and identified HDAC1 inhibition and p53 activation as novel signaling mechanisms. The study also created a dataset of AT(2)-receptor induced phospho-modified proteins, which can be used for further discoveries.
Article
Biochemistry & Molecular Biology
Natascha Skov, Carla L. Alves, Sidse Ehmsen, Henrik J. Ditzel
Summary: This study investigates the role of Aurora A and Bcl-xL in regulating basal B cell invasion in triple-negative breast cancer (TNBC). The results show that high levels of Aurora A and Bcl-xL promote metastasis, and inhibiting these proteins may suppress metastasis and improve patient survival in basal B TNBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Morten F. F. Gjerstorff, Sofie Traynor, Odd L. L. Gammelgaard, Simone Johansen, Christina B. B. Pedersen, Henrik J. J. Ditzel, Mikkel G. G. Terp
Summary: Breast cancer patient-derived xenograft (PDX) models have been shown to be excellent tools for studying and targeting myeloid-derived suppressive cells (MDSCs) in tumors. These models demonstrate active recruitment of MDSCs to the tumors and reflect clinical complexity seen in breast cancer patients, providing valuable insights for the development of novel therapeutic strategies.
Letter
Oncology
Leena Karimi, Carla L. Alves, Mikkel G. Terp, Martina Tuttolomondo, Neil Portman, Sidse Ehmsen, Lene E. Johansen, Martin Bak, Elgene Lim, Henrik J. Ditzel
CANCER COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Carla L. Alves, Henrik J. Ditzel
Summary: The PI3K/AKT/mTOR pathway plays a crucial role in estrogen receptor-positive breast cancer tumorigenesis and drug resistance, making it a highly attractive therapeutic target. Several inhibitors targeting this pathway are currently under clinical development. The recent approval of the PIK3CA isoform-specific inhibitor alpelisib and the pan-AKT inhibitor capivasertib, in combination with fulvestrant, has provided new treatment options for advanced estrogen receptor-positive breast cancer patients. However, the clinical development of multiple inhibitors and incorporating CDK4/6 inhibitors into the standard treatment has complicated the personalization of therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Qingqing Wu, Xiaoyang Luo, Mikkel G. Terp, Qingrun Li, Yuan Li, Lei Shen, Ying Chen, Kirstine Jacobsen, Trever G. Bivona, Haiquan Chen, Rong Zeng, Henrik J. Ditzel
Summary: Early recurrence is a major obstacle in prolonged postoperative survival for squamous cell lung carcinoma (SqCLC). DDX56 was identified as an independent prognostic biomarker in SqCLC patients, promoting early recurrence through post-transcriptional regulation of Wnt signaling genes via miRNA-mediated effects. These findings suggest DDX56 may help identify SqCLC patients at risk for early recurrence and could benefit from Wnt signaling-targeted therapies.