Review
Endocrinology & Metabolism
Amber J. Kiliti, Ghada M. Sharif, Mary Beth Martin, Anton Wellstein, Anna T. Riegel
Summary: Estrogen receptor alpha (ERα) plays a crucial role in the initiation and progression of most breast cancers. It regulates gene transcription through recruitment of coregulators, including Amplified in Breast Cancer 1 (AIB1). AIB1, an oncogene overexpressed in some breast cancers, is involved in tumor progression and resistance to endocrine therapy. This review provides an overview of the normal and pathological functions of AIB1, its actions dependent and independent of ERα, as well as its genomic conservation and protein evolution. The efforts to target AIB1 in the treatment of breast cancer are also discussed.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Zhiguo Niu, Jianing Fan, Fengzhe Chen, Huijie Yang, Xin Li, Ting Zhuang, Chunlei Guo, Qi Cao, Jian Zhu, Hui Wang, Qingsong Huang
Summary: Breast cancer is the most common malignancy in women globally. Abnormal expression of RBCK1 protein in breast tumors makes it a valuable diagnostic marker and drug target. Hypoxic regions in breast cancer activate the HIF1 pathway, influencing tumor recurrence and metastasis. Targeting RBCK1 could be a promising treatment strategy for ER-positive breast cancer.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Seng Chuan Tang, Quentin Lion, Olivier Peulen, Philippe Chariot, Arnaud Lavergne, Alice Mayer, Paula Allepuz Fuster, Pierre Close, Sebastian Klein, Alexandra Florin, Reinhard Buettner, Ivan Nemazanyy, Kateryna Shostak, Alain Chariot
Summary: COP1 acts as an oncogenic E3 ligase by promoting ERα signaling but also acts as a tumor suppressor candidate by preventing EMT, reflecting a dual role of COP1 in breast cancer that has sparked widespread interest in the academic community.
Article
Oncology
Rima Patel, Malin Hovstadius, Melanie W. Kier, Erin L. Moshier, Brittney S. Zimmerman, Krystal Cascetta, Shabnam Jaffer, Joseph A. Sparano, Amy Tiersten
Summary: There is no significant correlation between Ki67 and Oncotype DX RS in early-stage hormone receptor-positive breast cancer patients, although there is fair agreement between high Ki67 values and high RS values.
Review
Oncology
Charles Dai, Leif W. Ellisen
Summary: Aberrant estrogen receptor (ER) signaling plays a key role in the development of many breast cancers. The androgen receptor (AR), similar to ER, is frequently expressed in breast cancer and has been considered as a potential therapeutic target. However, the understanding of androgen signaling in breast cancer is incomplete and there are conflicting findings regarding the role of AR. This article summarizes the current understanding of AR biology and recent investigations into AR-directed therapies in breast cancer.
Article
Medicine, Research & Experimental
Sheila Almaraz Postigo, Juan Carlos Montero
Summary: In this study, the researchers found that Neuregulins (NRGs) regulate estrogen receptor α (ERα) in breast cancer cells through multiple mechanisms. NRGs activate the PI3K/AKT/mTOR, ERK1/2, and ERK5 pathways, leading to phosphorylation of ERα and down-regulation of its expression. NRGs also confer resistance to fulvestrant in breast cancer cells. However, this resistance can be reversed by simultaneously inhibiting these three pathways.
Review
Biochemistry & Molecular Biology
Lea Clusan, Francois Ferriere, Gilles Flouriot, Farzad Pakdel
Summary: Breast cancer, the most common and deadliest cancer among women worldwide, is closely associated with estrogen signaling. Hormone therapy using antiestrogens is the standard treatment, but resistance inevitably occurs through various biological mechanisms. Understanding the estrogen pathway is crucial for the development of new therapies for hormone-dependent breast cancer. This mini-review summarizes the current literature on estrogen receptors in breast cancer, including their signalization, mechanisms of action, and clinical implications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Aditi S. Khatpe, Adedeji K. Adebayo, Christopher A. Herodotou, Brijesh Kumar, Harikrishna Nakshatri
Summary: Breast cancers are broadly classified into two subtypes: estrogen receptor-positive and estrogen receptor-negative. While approximately 70% of breast cancers are estrogen receptor-positive, this type is more common in postmenopausal women. Although the majority of estrogen receptor-positive breast cancers respond to anti-estrogens, approximately 30% may recur.
Article
Multidisciplinary Sciences
Rawan Al-Nemari, Abir Ben Bacha, Abdulrahman Al-Senaidy, Mikhlid H. Almutairi, Maha Arafah, Hadel Al-Saran, Nael Abutaha, Abdelhabib Semlali
Summary: The leaf extract of A. squamosa has shown strong anticancer activity in inhibiting cell proliferation and inducing apoptosis. In vivo experiments have demonstrated its significant therapeutic effect on breast cancer, suggesting its potential as a novel drug for future development.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2022)
Review
Endocrinology & Metabolism
Xiaoyong Fu, Carmine De Angelis, Rachel Schiff
Summary: Cancer immunology is a rapidly expanding field in cancer research, and the immune system plays an important role in the development of breast cancer. IFN signaling is critical in determining therapy response and outcome of breast cancer patients, depending on the subtype. The role of tumor cell-inherent IFN signaling in the breast cancer microenvironment could influence therapy response with protumor activities.
Article
Cell Biology
Virginia Solar Fernandez, Marco Fiocchetti, Manuela Cipolletti, Marco Segatto, Paolo Cercola, Annalisa Massari, Sabrina Ghinassi, Francesco Cavaliere, Maria Marino
Summary: The study evaluated the levels and localization of NGB in ER alpha+ breast ductal carcinoma tissue, finding a strong association between NGB accumulation, ER alpha, AKT activation, and the G3 grade, while no association with the menopausal state was evident. Analysis of the data set supported the idea that NGB accumulation could be linked to tumor cell aggressiveness (high grade) and resistance to treatment.
Article
Plant Sciences
Yuhong Li, Shuying Hu, Yueqi Chen, Xing Zhang, Hanchi Gao, Jing Tian, Jian Chen
Summary: A novel estrogen receptor-alpha splice variant ER-α30 was found to be primarily localized in the nucleus of triple-negative breast cancer (TNBC) cells. ER-α30 was significantly overexpressed in breast cancer tissues of ER- and progesterone receptor (PR)-negative subtype as well as in TNBC cell lines compared to normal breast cell line MCF10A. ER-α30 overexpression promoted TNBC cell viability, migration, invasion, and epithelial-mesenchymal transition, while knockdown of ER-α30 had the opposite effects. Calycosin could suppress ER-α30 expression and inhibit TNBC growth and metastasis.
Article
Biology
Juan P. Munoz, Gloria M. Calaf
Summary: Acetylcholine (ACh) can activate the MAPK/ERK and PI3K/Akt pathways, induce p-ERα expression and nuclear translocation in breast cancer cell lines. However, ACh and 17β-estradiol have different mechanisms of action, and ACh can enhance cell viability and induce overexpression of specific EMT markers.
Review
Oncology
Paulina Miziak, Marzena Baran, Ewa Blaszczak, Alicja Przybyszewska-Podstawka, Joanna Kalafut, Jolanta Smok-Kalwat, Magdalena Dmoszynska-Graniczka, Michal Kielbus, Andrzej Stepulak
Summary: ER signaling is a critical regulator in breast cancer and other hormone-sensitive cancers. This article reviews the mechanism of ER-dependent downstream signaling in breast cancer and discusses the clinical implications of ER signaling, including potential endocrine therapies. The challenges associated with therapy resistance caused by acquired ER mutations and potential strategies to overcome them are also discussed.
Article
Biochemistry & Molecular Biology
Jiahao Chen, Jingxin Liu, Pengguihang Zeng, Cai Zhao, Xinyi Liu, Jun Sun, Jia Wang, Peihang Fang, Wenjie Chen, Junjun Ding
Summary: Estrogen (E2) and BRCA1 deficiency synergistically induce DNA damage in breast cancer cells, possibly involving transcriptional activation of ER genes and changes in DNA damage distribution.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Slavomir Krajnak, Jana Krajnakova, Katharina Anic, Katrin Almstedt, Anne-Sophie Heimes, Valerie Catherine Linz, Amelie Loewe, Mona Wanda Schmidt, Annette Hasenburg, Marcus Schmidt, Marco Johannes Battista
Summary: In this retrospective unicenter study, we demonstrated real-word data on metronomic chemotherapy in metastatic breast cancer (MBC). The results showed that metronomic chemotherapy was effective and well tolerated in MBC patients, suggesting it as a valuable treatment option.
Article
Oncology
Magdalena Keller, Katharina Rohlf, Annika Glotzbach, Gregor Leonhardt, Simon Lueke, Katharina Derksen, Oezlem Demirci, Defne Goecener, Mohammad AlWahsh, Joerg Lambert, Cecilia Lindskog, Marcus Schmidt, Walburgis Brenner, Matthias Baumann, Eldar Zent, Mia-Lisa Zischinsky, Birte Hellwig, Katrin Madjar, Joerg Rahnenfuehrer, Nina Overbeck, Joerg Reinders, Cristina Cadenas, Jan. G. G. Hengstler, Karolina Edlund, Rosemarie Marchan
Summary: This study found that EDI3 is highly expressed in ER-HER2+ breast tumors, and its expression and activity are also highest in ER-HER2+ breast cancer cell lines. Silencing HER2 and inhibiting HER2 signaling can decrease EDI3 expression. Silencing EDI3 can selectively decrease cell viability in ER-HER2+ cells. Therefore, EDI3 may be a potential therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2+ breast cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Obstetrics & Gynecology
Volkmar Mueller, Peter A. Fasching, Naiba Nabieva, Tanja N. Fehm, Marc Thill, Marcus Schmidt, Thorsten Kuehn, Maggie Banys-Paluchowski, Erik Belleville, Ingolf Juhasz-Boess, Michael Untch, Hans-Christian Kolberg, Nadia Harbeck, Bahriye Aktas, Elmar Stickeler, Julia Kreuzeder, Andreas D. Hartkopf, Wolfgang Janni, Nina Ditsch
Summary: In premenopausal patients with hormone receptor-positive, HER2-negative breast cancer, adjuvant endocrine therapy presents special considerations in those with ovarian function. Treatment options such as tamoxifen with or without a GnRH analog, and aromatase inhibitors with a GnRH analog are available. Previous chemotherapy affects ovarian function. Aromatase inhibitors (+ GnRH analogs) and GnRH analogs in combination with tamoxifen are indicated for patients at increased risk of recurrence. However, current guidelines lack clear definitions for intermediate or high risk, leading to individualized therapy decisions. Variability exists in the use of aromatase inhibitors + GnRH analogs at national and international levels. This review provides a summary of completed studies, ongoing multigene testing studies, discusses current rationale, and looks towards future questions.
GEBURTSHILFE UND FRAUENHEILKUNDE
(2023)
Article
Medicine, Research & Experimental
Tom Degenhardt, Peter A. Fasching, Diana Lueftner, Volkmar Mueller, Christoph Thomssen, Christian Schem, Isabell Witzel, Thomas Decker, Hans Tesch, Sherko Kuemmel, Christoph Uleer, Rachel Wuerstlein, Oliver Hoffmann, Mathias Warm, Norbert Marschner, Timo Schinkoethe, Ronald E. Kates, Johannes Schumacher, Burkhard Otremba, Matthias Zaiss, Nadia Harbeck, Marcus Schmidt
Summary: This article discusses an important issue in breast cancer treatment, which is medication adherence. The use of an eHealth-based platform to support treatment management and physician-patient interaction can help improve patients' adherence to treatment and quality of life.
Article
Oncology
Christoph Thomssen, Martina Vetter, Eva J. J. Kantelhardt, Christoph Meisner, Marcus Schmidt, Pierre M. M. Martin, Florian Clatot, Doris Augustin, Volker Hanf, Daniela Paepke, Wolfgang Meinerz, Gerald Hoffmann, Wolfgang Wiest, Fred C. G. J. Sweep, Manfred Schmitt, Fritz Jaenicke, Sibylle Loibl, Gunter von Minckwitz, Nadia Harbeck
Summary: The NNBC-3 Europe trial aimed to assess the risk of recurrence in node-negative breast cancer patients and to determine whether taxanes can improve disease-free survival in high-risk patients. The study found that patients with high-risk node-negative breast cancer have a favorable prognosis in the first few years after diagnosis regardless of the type of chemotherapy.
Article
Biochemistry & Molecular Biology
Anne-Sophie Heimes, Natali Riedel, Katrin Almstedt, Slavomir Krajnak, Roxana Schwab, Kathrin Stewen, Antje Lebrecht, Marco Johannes Battista, Walburgis Brenner, Annette Hasenburg, Marcus Schmidt
Summary: The higher immunogenicity of triple-negative breast cancer (TNBC) compared to other subtypes is due to its higher mutational load. In this study, the prognostic significance of tumor-infiltrating plasma cells in TNBC patients was analyzed. The expression of CD38 and Ig kappa C markers was used to evaluate the infiltration of plasma cells. It was found that higher tumor infiltration with CD38-positive plasma cells was associated with longer metastasis-free survival. CD38 was identified as an independent prognostic factor. The nodal status also had a significant impact on prognosis. Higher expression of Ig kappa C was associated with a better outcome, although not statistically significant. The study also showed a correlation between plasma cell infiltration and the BRCA mutation status.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hans-Joachim Lueck, Marcus Schmidt, Tobias Hesse, Oliver Hoffmann, Bernhard J. Heinrich, Tjoung-Won Park-Simon, Eva-Maria Grischke, Rudolf Weide, Harald Mueller-Huesmann, Kerstin Luedtke-Heckenkamp, Dorothea Fischer, Cosima Zemlin, Matthias Koegel, Jane Wu, Helga Schmitz, Christian Engelbrecht, Christian Jackisch
Summary: The study assessed the incidence and severity of peripheral neuropathy (PN) in breast cancer patients treated with eribulin. The rates of any grade and grade ≥3 PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.
Article
Oncology
Herjan J. T. Coelingh Bennink, Iman J. Schultz, Marcus Schmidt, V. Craig Jordan, Paula Briggs, Jan F. M. Egberts, Kristina Gemzell-Danielsson, Ludwig Kiesel, Kirsten Kluivers, Jan Krijgh, Tommaso Simoncini, Frank Z. Stanczyk, Robert D. Langer
Summary: Multiple factors, including reproductive hormones, are associated with a woman's risk of developing breast cancer (BC). This review explores the correlation between ovulatory menstrual cycles (MCs) and BC risk. Variations in MC frequency and interference with MCs through genetics, pathology, and pharmaceutical interventions suggest a strong connection between BC risk and the total number of MCs throughout a woman's lifetime. The presence of MCs significantly increases BC risk, while situations without MCs show a substantial reduction in risk. The hormone progesterone (P4) plays an essential role, as normal breast epithelium is strongly stimulated by P4 during the MC, while estradiol (E2) has minimal effects. The repeated stimulation of breast epithelium by P4 during MCs may contribute to the accumulation of mutations and the development of breast tumors over several decades. This suggests that P4 is a crucial factor in a woman's lifetime BC risk, and that breast tumors arising during hormonal contraception or after menopause are likely the result of the growth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.
BREAST CANCER RESEARCH
(2023)
Review
Oncology
Annika Droste, Marcus Schmidt
Summary: Advanced hormone receptor-positive breast cancer is a common and incurable disease in women. Inhibiting the hormonal growth signals through anti-hormonal therapy offers a potential solution, although drug resistance remains a challenge. Molecularly targeted substances, such as cyclin-dependent kinase inhibitors, improve survival rates and enhance endocrine therapy's effectiveness. Targeting the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin pathway shows promise in overcoming endocrine resistance. Developing new therapies to combat endocrine resistance is an urgent challenge, and this review examines promising approaches.
JOURNAL OF CANCER METASTASIS AND TREATMENT
(2023)
Article
Obstetrics & Gynecology
Marcus Schmidt, Carsten Denkert, Kerstin Rhiem, Thomas Decker, Sibylle Loibl
Summary: This article presents the evidence for personalized therapy of advanced breast cancer and explains the standardized classifications of treatment relevance. The treatment relevance of genomic alterations is assessed by professional societies. Evidence-based personalized medicine can improve the treatment outcomes for metastatic breast cancer patients.
Article
Obstetrics & Gynecology
Josche van der Ven, Valerie Catherine Linz, Katharina Anic, Mona Wanda Schmidt, Amelie Loewe, Slavomir Krajnak, Marcus Schmidt, Stefan Kommoss, Barbara Schmalfeldt, Jalid Sehouli, Annette Hasenburg, Marco Johannes Battista
Summary: This study investigated the clinical management of patients with pelvic high-grade serous carcinoma (HGSC) and its precursor lesion serous tubal intraepithelial carcinoma (STIC) in Germany. The survey showed significant inconsistency in the management of STIC patients, highlighting the need for prospective research to clarify the clinical impact of STIC lesions and their management.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2023)
Article
Obstetrics & Gynecology
Marcus Schmidt
Summary: This article discusses the principles and evidence for vaccination strategies in breast cancer, highlighting their potential to improve patient survival.
Article
Oncology
Thomas Decker, Kerstin Luedtke-Heckenkamp, Luidmila Melnichuk, Nader Hirmas, Kristina Luebbe, Mark-Oliver Zahn, Marcus Schmidt, Carsten Denkert, Ralf Lorenz, Volkmar Mueller, Dirk-Michael Zahm, Christoph Mundhenke, Stefan Bauer, Marc Thill, Peter Seropian, Natalie Filmann, Sibylle Loibl
Summary: This study evaluated the efficacy and safety of adding ribociclib to maintenance endocrine therapy (ET) following palliative chemotherapy in patients with hormone receptor positive/human epidermal growth factor 2 negative metastatic breast cancer. The results showed that the addition of ribociclib significantly prolonged progression-free survival and had a good clinical benefit rate. The safety profile of ribociclib combined with ET was acceptable compared to ET alone.
Review
Obstetrics & Gynecology
Volkmar Mueller, Peter A. Fasching, Naiba Nabieva, Tanja N. Fehm, Marc Thill, Marcus Schmidt, Thorsten Kuehn, Maggie Banys-Paluchowski, Erik Belleville, Ingolf Juhasz-Boess, Michael Untch, Hans-Christian Kolberg, Nadia Harbeck, Bahriye Aktas, Elmar Stickeler, Julia Kreuzeder, Andreas D. Hartkopf, Wolfgang Janni, Nina Ditsch
Summary: For breast cancer patients with existing ovarian function, there are special considerations for adjuvant endocrine therapy. However, there is currently no clear definition of intermediate or high risk patients in national and international guidelines, leading to individualized therapy decisions.
GEBURTSHILFE UND FRAUENHEILKUNDE
(2023)
Article
Obstetrics & Gynecology
Katharina Anic, Jakub Varchola, Mona Wanda Schmidt, Roxana Schwab, Valerie Catherine Linz, Marcus Schmidt, Roland Hardt, Erik Kristoffer Hartmann, Christian Ruckes, Annette Hasenburg, Marco Johannes Battista
Summary: This study evaluated the association between preoperative frailty assessment and in-hospital complications in ovarian cancer patients. The results showed that using the G8 Score for frailty assessment can predict the occurrence of postoperative complications, while other assessment tools cannot. Therefore, standardized preoperative frailty assessment is of great importance for surgical decision-making in elderly cancer patients.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2023)