scholarly journals Incorporating Genomic and Genetic Testing into the Treatment of Metastatic Luminal Breast Cancer

Breast Care ◽  
2021 ◽  
pp. 1-7
Author(s):  
Sabine Grill ◽  
Evelyn Klein
Keyword(s):  
Breast Cancer ◽  
Personalized Medicine ◽  
Disease Management ◽  
Molecular Subtype ◽  
Individual Treatment ◽  
Luminal Breast Cancer ◽  
Genomic Testing ◽  
Integral Component ◽  
New Challenges

<b><i>Background:</i></b> Treatment of patients with luminal metastatic breast cancer (MBC) has become even more complex over the last few years as molecular profiling has begun to alter disease management. It is well accepted that MBC is not curable but is treatable. Today we are able to prolong progression-free survival and partly overall survival with targeted and more individual treatment strategies adjusted according to the molecular subtype. <b><i>Summary:</i></b> Genetic and genomic testing has become therapeutically relevant in luminal MBC and is therefore an integral component within the treatment spectrum. By now, germline testing of <i>BRCA</i>1 and <i>BRCA</i>2 and somatic testing for <i>PIK3CA</i> mutations are inevitable elements in disease management and the current state of the art in luminal MBC patients. Furthermore, testing of <i>ESR1</i> resistance mutation, <i>ERBB2</i> mutation, microsatellite instability, and neurotrophic tyrosine receptor kinase (NTRK) gene fusion (mainly in secretory breast cancer) has recently gained increasing attention. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities. The following review summarizes current developments in genetic and genomic testing in luminal MBC. <b><i>Key Messages:</i></b> In luminal MBC genomics have become an integral component within the spectrum of oncological treatment establishing novel therapeutic facilities. Further developments in treatment personalization adjusted according to the molecular subtype should become increasingly important in order to enhance the progress of de-escalation of chemotherapy in luminal MBC. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities.

scholarly journals Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

CNS Oncology ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. CNS65
Author(s):  
Leonor Fernandes ◽  
Leonor Vasconcelos de Matos ◽  
Débora Cardoso ◽  
Marlene Saraiva ◽  
Renata Medeiros-Mirra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Leptomeningeal Carcinomatosis ◽  
Luminal Breast Cancer ◽  
Leptomeningeal Disease ◽  
Targeted Agents ◽  
Published Evidence ◽  
Cns Activity ◽  
Evidenced Based

Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

scholarly journals (Radio)Theranostic Patient Management in Oncology Exemplified by Neuroendocrine Neoplasms, Prostate Cancer, and Breast Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 39
Author(s):  
Irina Velikyan
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Nuclear Medicine ◽  
Personalized Medicine ◽  
Patient Management ◽  
Neuroendocrine Neoplasms ◽  
Medicine Development ◽  
Oncological Patients

The role of nuclear medicine in the management of oncological patients has expanded during last two decades. The number of radiopharmaceuticals contributing to the realization of theranostics/radiotheranostics in the context of personalized medicine is increasing. This review is focused on the examples of targeted (radio)pharmaceuticals for the imaging and therapy of neuroendocrine neoplasms (NENs), prostate cancer, and breast cancer. These examples strongly demonstrate the tendency of nuclear medicine development towards personalized medicine.

scholarly journals Breast Cancer in Young Women: Status Quo and Advanced Disease Management by a Predictive, Preventive, and Personalized Approach

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1791 ◽  
Author(s):  
Erik Kudela ◽  
Marek Samec ◽  
Peter Kubatka ◽  
Marcela Nachajova ◽  
Zuzana Laucekova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Personalized Medicine ◽  
Disease Management ◽  
Young Women ◽  
Screening Tools ◽  
Molecular Signature ◽  
Young Females ◽  
Preventive And Personalized Medicine ◽  
Personalized Approach ◽  
And Personalized Medicine

Why does healthcare of breast cancer (BC) patients, especially in a young population, matter and why are innovative strategies by predictive, preventive, and personalized medicine (PPPM) strongly recommended to replace current reactive medical approach in BC management? Permanent increase in annual numbers of new BC cases with particularly quick growth of premenopausal BC patients, an absence of clearly described risk factors for those patients, as well as established screening tools and programs represent important reasons to focus on BC in young women. Moreover, "young" BC cases are frequently "asymptomatic", difficult to diagnose, and to treat effectively on time. The objective of this article is to update the knowledge on BC in young females, its unique molecular signature, newest concepts in diagnostics and therapy, and to highlight the concepts of predictive, preventive, and personalized medicine with a well-acknowledged potential to advance the overall disease management.

scholarly journals The role of ultrasonographic findings to predict molecular subtype, histologic grade, and hormone receptor status of breast cancer

2015 ◽  
Vol 21 (6) ◽  
pp. 448-453 ◽  
Author(s):  
Filiz Celebi ◽  
Kezban Nur Pilanci ◽  
Cetin Ordu ◽  
Filiz Agacayak ◽  
Gul Alco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Molecular Subtype ◽  
Hormone Receptor Status ◽  
Histologic Grade ◽  
Receptor Status

scholarly journals MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000937
Author(s):  
Annalisa Petrelli ◽  
Sara Erika Bellomo ◽  
Ivana Sarotto ◽  
Franziska Kubatzki ◽  
Paola Sgandurra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Endocrine Therapy ◽  
Molecular Subtype ◽  
Molecular Taxonomy ◽  
Endocrine Resistance ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Luminal Breast Cancer ◽  
Luminal A

PurposeOverexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer.MethodsmiR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype.ResultsBaseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype.ConclusionsOur findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer.

scholarly journals Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 995 ◽  
Author(s):  
Shristi Bhattarai ◽  
Sergey Klimov ◽  
Karuna Mittal ◽  
Uma Krishnamurti ◽  
Xiaoxian Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Good Prognosis ◽  
Prognostic Role ◽  
Primary Tumors ◽  
Total N

Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients’ prognosis. Methods: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. Results: AR status shows population-specific patterns of association with patients’ overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.

scholarly journals PREDICTIVE RELAPSE MODEL IN PATIENTS WITH LUMINAL HER2-NEGATIVE BREAST CANCER

2020 ◽  
pp. 61-73
Author(s):  
M.Kh. Torosyan ◽  
T.V. Shevchenko ◽  
V.V. Rodionov ◽  
Yu.G. Savinov ◽  
Yu.A. Veryaskina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Model ◽  
Prognostic Index ◽  
Cancer Recurrence ◽  
Disease Stage ◽  
Luminal Breast Cancer ◽  
Her2 Overexpression ◽  
Ki 67 ◽  
Expression Levels

Luminal HER2-negative breast cancer (BC) detected at early stages is characterized by a relatively favorable course. However, in some cases, there may be a relapse of the disease regardless of the treatment. The aim of the study was to identify predictors of recurrence of primary resectable luminal HER2-negative breast cancer. Materials and Methods. The authors examined biopsies of patients’ breast tumors (n=158) with luminal HER2-negative breast cancer, stage T1-2N0-1M0, as well as anamnestic data of patients. All women were divided into 2 groups: with disease recurrence within the next 5 years after surgery (n=53) and relapse-free patients (n=105). Macroscopic tumor characteristics, its malignancy, total malignancy score, Nottingham prognostic index, Ki-67, expression of receptors for estrogen and progesterone and their influence on relapse were studied. The authors analyzed expression levels of miRNA (miRNA-21, miRNA-221, miRNA-222, miRNA-155, miRNA-205, miRNA-20a, miRNA-125b, miRNA-146b, miRNA-200a) in tumor tissues. Statistical data processing was performed using Statistica 7 (StatSoft Inc., USA) and MedCalc (version 15.2) software. Results. Comparative analysis of miRNA expression levels between groups of patients with recurrent breast cancer (n=21) and relapse-free patients (n=20) revealed a statistically significant increase in the expression levels of miRNA-21, miRNA-205, miRNA-146b, and miRNA-200a in the group with recurrent disease. The authors established the predictive role of the ratios of the expression levels of potentially oncogenic and tumor suppressive miRNA-21/miRNA-155 and miRNA-21/miRNA-205, as well as the role of miRNA-20a in breast cancer recurrence in combination with Ki-67, disease stage, and primary tumor size. Based on the data obtained, they developed a prognostic model to determine the recurrence of primary operable luminal HER2-negative breast cancer. Conclusion. The created prognostic model allows to clearly stratify the prognosis of primary operable luminal HER2-negative breast cancer. Keywords: primary resectable luminal breast cancer without HER2 overexpression, recurrence prognosis, miRNA. Люминальный HER2-негативный рак молочной железы (РМЖ), выявленный на ранних стадиях, характеризуется относительно благоприятным течением. Однако в ряде случаев возникает рецидив заболевания независимо от проведенного лечения. Цель исследования – выявить предикторы рецидивирования первично операбельного люминального HER2-негативного РМЖ. Материалы и методы. Исследовались биоптаты опухолей молочной железы пациенток (n=158) с люминальным HER2-негативным РМЖ стадии T1-2N0-1M0, а также анамнестические данные пациенток. Все женщины были разделены на 2 группы: с рецидивом заболевания в течение последующих 5 лет после проведения операции (n=53) и с безрецидивным течением (n=105). Изучены макроскопические характеристики опухоли, степень злокачественности, суммарный балл злокачественности, Ноттингемский прогностический индекс, Ki-67, экспрессия рецепторов к эстрогену и прогестерону и их влияние на возникновение рецидива. Проведен анализ уровней экспрессии миРНК (миРНК-21, миРНК-221, миРНК-222, миРНК-155, миРНК-205, миРНК-20а, миРНК-125b, миРНК-146b, миРНК-200a) в тканях опухолей. Статистическая обработка данных произведена с помощью программ Statistica 7 (StatSoft Inc., США) и MedCalc (версия 15.2). Результаты. Сравнительный анализ уровней экспрессии миРНК между группами пациенток с рецидивом РМЖ (n=21) и безрецидивным течением (n=20) выявил статистически значимое повышение уровней экспрессии миРНК-21, миРНК-205, миРНК-146b и миРНК-200a в группе с рецидивом заболевания. Установлена предсказывающая роль соотношений уровней экспрессии потенциально онкогенных и онкосупрессорных миРНК-21/миРНК-155 и миРНК-21/миРНК-205, а также роль миРНК-20a в возникновении рецидива РМЖ в сочетании с Кi-67, стадией заболевания, размером первичной опухоли. На основе полученных данных разработана прогностическая модель определения рецидива первично операбельного люминального HER2-негативного РМЖ. Выводы. Созданная прогностическая модель позволяет четко стратифицировать прогноз первично операбельного люминального HER2-негативного РМЖ. Ключевые слова: первично операбельный люминальный рак молочной железы без гиперэкспрессии HER2, прогноз рецидива, миРНК.

scholarly journals Dermatan Sulfate Affects Breast Cancer Cell Function via the Induction of Necroptosis

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 173
Author(s):  
Grzegorz Wisowski ◽  
Adam Pudełko ◽  
Krystyna Olczyk ◽  
Monika Paul-Samojedny ◽  
Ewa M. Koźma
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Dermatan Sulfate ◽  
Variable Structure ◽  
Structural Features ◽  
Luminal Breast Cancer ◽  
Binding Properties

Dermatan sulfate (DS) is widespread in the extracellular matrix (ECM) of animal tissues. This glycosaminoglycan is characterized by a variable structure, which is reflected in the heterogeneity of its sulfation pattern. The sulfate groups are responsible for the binding properties of DS, which determine an interaction profile of this glycan. However, the detailed role of DS in biological processes such as the neoplasm is still poorly understood. The aim of the study was to assess the effects of the structural variants of DS on breast cancer cells. We found that DS isoforms from normal and fibrotic fascia as well as from intestinal mucosa were able to quickly induce oxidative stress in the cytoplasm and affect the mitochondrial function in luminal breast cancer cells. Moreover, the variants caused the necroptosis of the cells most likely via the first of these mechanisms. This death was responsible for a reduction in the viability and number of breast cancer cells. However, the dynamics and intensity of all of the DS variants-triggered effects were strongly dependent on the cell type and the structure of these molecules. The most pronounced activity was demonstrated by those variants that shared structural features with the DS from the tumor niche.

scholarly journals Tumorigenic and Metastatic Role of CD44−/low/CD24−/low Cells in Luminal Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1239 ◽  
Author(s):  
Rajeev Vikram ◽  
Wen Cheng Chou ◽  
Shih-Chieh Hung ◽  
Chen-Yang Shen
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Diagnostic Tools ◽  
Breast Cancer Cell Lines ◽  
Luminal Breast Cancer ◽  
Cancer Subtypes ◽  
Tumorigenic Potential ◽  
Mcf 7

Cells with high CD44 but low CD24 expression (CD44high/CD24−/low) and high aldehyde dehydrogenase activity (ALDHbr) are widely considered to be drivers of metastasis, therapy resistance and tumor recurrence in breast cancer. However, the role of the CD44high/CD24−/low and ALDHbr phenotypes in identifying tumorigenic cells in breast cancer remains controversial due to the discrepancy in their distribution and tumorigenic potential in intrinsic breast cancer subtypes. In this study, we analyzed the cells expressing these markers in six different breast cancer cell lines representing major breast cancer subtypes (T47D, MCF-7, BT-474, AU-565, Hs578T and MDA-MB-231). CD44high/CD24−/low, ALDHbr and CD44−/low/CD24−/low cell populations were isolated by flow cytometry and analyzed for hallmark stem cell characteristics of differentiation, migration, invasiveness and metastasis using in vitro and in vivo techniques. Our results demonstrate that the CD44−/low/CD24−/low cell population, which is enriched in luminal cell lines (T47D, MCF-7 and BT-474), possesses metastatic and tumorigenic properties. We also show that, contrary to previous claims, the expression of the ALDH1 isoform ALDH1A1 does not affect the tumorigenic potential of cell lines with high ALDH activity (BT-474 and AU-565). Further transcriptomic and clinical studies are needed to determine the potential of these markers as early diagnostic tools and treatment targets.

scholarly journals A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

Oncogene ◽  
2015 ◽  
Vol 34 (36) ◽  
pp. 4777-4790 ◽  
Author(s):  
S Castillo-Lluva ◽  
L Hontecillas-Prieto ◽  
A Blanco-Gómez ◽  
M del Mar Sáez-Freire ◽  
B García-Cenador ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Cancer Development ◽  
Luminal Breast Cancer ◽  
Breast Cancer Development ◽  
Postlactational Involution
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