scholarly journals miRNA Expression Profiles in Luminal A Breast Cancer—Implications in Biology, Prognosis, and Prediction of Response to Hormonal Treatment

2020 ◽  
Vol 21 (20) ◽  
pp. 7691
Author(s):  
Erik Kudela ◽  
Marek Samec ◽  
Lenka Koklesova ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mirna Expression ◽  
Early Stage ◽  
Expression Profiles ◽  
Classification Systems ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Altered Expression ◽  
Cancer Subtypes

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.

scholarly journals Genomic Signatures in Luminal Breast Cancer

Breast Care ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. 355-365
Author(s):  
Julian Puppe ◽  
Tabea Seifert ◽  
Christian Eichler ◽  
Henryk Pilch ◽  
Peter Mallmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Throughput Sequencing ◽  
Early Stage ◽  
Intrinsic Subtype ◽  
Luminal Breast Cancer ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Molecular Tests ◽  
Immunohistochemical Markers

Background: Breast cancer is a very heterogeneous disease and luminal breast carcinomas represent the hormone receptor-positive tumors among all breast cancer subtypes. In this context, multigene signatures were developed to gain further prognostic and predictive information beyond clinical parameters and traditional immunohistochemical markers. Summary: For early breast cancer patients these molecular tools can guide clinicians to decide on the extension of endocrine therapy to avoid over- and undertreatment by adjuvant chemotherapy. Beside the predictive and prognostic value, a few genomic tests are also able to provide intrinsic subtype classification. In this review, we compare the most frequently used and commercially available molecular tests (OncotypeDX®, MammaPrint®, Prosigna®, EndoPredict®, and Breast Cancer IndexSM). Moreover, we discuss the clinical utility of molecular profiling for advanced breast cancer of the luminal subtype. Key Messages: Multigene assays can help to de-escalate systemic therapy in early-stage breast cancer. Only the Oncotype DX® and MammaPrint®test are validated by entirely prospective and randomized phase 3 trials. More clinical evidence is needed to support the use of genomic tests in node-positive disease. Recent developments in high-throughput sequencing technology will provide further insights to understand the heterogeneity of luminal breast cancers in early-stage and metastatic disease.

scholarly journals Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

2019 ◽  
Vol 7 (21) ◽  
pp. 3534-3539
Author(s):  
Nada A. S. Alwan ◽  
Furat N. Tawfeeq
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Significant Difference

BACKGROUND: Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour. AIM: To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions. PATIENTS AND METHODS: The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes. RESULTS: The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement. CONCLUSION: The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

scholarly journals PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
S. Bonin ◽  
D. Pracella ◽  
R. Barbazza ◽  
I. Dotti ◽  
S. Boffo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Expression Profiles ◽  
Mrna Level ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Expression Levels ◽  
Node Involvement

Lymph node metastatic involvement persists to be among the most important predictors of recurrence and survival in breast carcinoma (BC). This study is aimed at investigating possible gene expression differences in primary BC between patients with or without lymph node involvement at the time of diagnosis. In a retrospective study, we investigated the potential prognostic role of 9 candidate biomarkers at the mRNA level in a cohort of 305 breast cancer patients, 151 lymph node-negative (LN-) and 154 lymph node-positive (LN+) individuals. The analyzed genes belonged to the RAS pathway (RAF1, ERBB2, PIK3CB, AKT1, AKT2, and AKT3), RB pathway (RB1 and CDK2), and cellular differentiation (KRT8). Their expression profiles were investigated by RT-qPCR and were correlated to immunohistochemically based molecular subtypes and BC clinical and pathological features. The differential expression of several genes in the primary tumor tissue was related to the LN involvement. Some of those genes, including PIK3CB, RB1, and AKT3, were more expressed in LN- BC patients, while some others, notably ERBB2 and AKT1, in LN+ ones. Among the candidate biomarkers, the expression levels of AKT isoforms influenced also patients’ survival rates. In detail, higher expression levels of AKT1 and AKT2 negatively influenced overall patients’ survival, and in particular, AKT2 expression levels defined a group of luminal B BC patients with shorter cancer-specific survival. On the contrary, longer cancer-specific survival was recorded in luminal A BC patients with higher expression levels of AKT3. That finding was also confirmed by Cox multivariate analysis. The same AKT3 resulted to be a possible candidate predictive biomarker for Tamoxifen response. In conclusion, our study highlighted the complex regulation of the PI3K/AKT pathway in BC and its differences in BC patients with and without lymph node involvement.

Metastatic Behavior of Breast Cancer Subtypes

2010 ◽  
Vol 28 (20) ◽  
pp. 3271-3277 ◽  
Author(s):  
Hagen Kennecke ◽  
Rinat Yerushalmi ◽  
Ryan Woods ◽  
Maggie Chon U. Cheang ◽  
David Voduc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Metastases ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Breast Cancer Subtypes ◽  
Early Stage Breast Cancer ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Metastatic Sites

Purpose Prognostic and predictive factors are well established in early-stage breast cancer, but less is known about which metastatic sites will be affected. Methods Patients with early-stage breast cancer diagnosed between 1986 and 1992 with archival tissue were included. Subtypes were defined as luminal A, luminal B, luminal/human epidermal growth factor receptor 2 (HER2), HER2 enriched, basal-like, and triple negative (TN) nonbasal. Distant sites were classified as brain, liver, lung, bone, distant nodal, pleural/peritoneal, and other. Cumulative incidence curves were estimated for each site according to competing risks methods. Association between the site of relapse and subtype was assessed in multivariate models using logistic regression. Results Median follow-up time among 3,726 eligible patients was 14.8 years. Median durations of survival with distant metastasis were 2.2 (luminal A), 1.6 (luminal B), 1.3 (luminal/HER2), 0.7 (HER2 enriched), and 0.5 years (basal-like; P < .001). Bone was the most common metastatic site in all subtypes except basal-like tumors. In multivariate analysis, compared with luminal A tumors, luminal/HER2 and HER2-enriched tumors were associated with a significantly higher rate of brain, liver, and lung metastases. Basal-like tumors had a higher rate of brain, lung, and distant nodal metastases but a significantly lower rate of liver and bone metastases. TN nonbasal tumors demonstrated a similar pattern but were not associated with fewer liver metastases. Conclusion Breast cancer subtypes are associated with distinct patterns of metastatic spread with notable differences in survival after relapse.

MicroRNA involvement in the pathogenesis and management of breast cancer

2009 ◽  
Vol 62 (5) ◽  
pp. 422-428 ◽  
Author(s):  
S M Khoshnaw ◽  
A R Green ◽  
D G Powe ◽  
I O Ellis
Keyword(s):  
Breast Cancer ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Treatment Strategies ◽  
Molecular Classification ◽  
Mature Mirnas ◽  
Protein Coding ◽  
Cancer Subtypes ◽  
Mirna Expression Profiles ◽  
Regulatory Functions

MicroRNAs (miRNAs) are a highly abundant class of endogenous small non-coding RNAs (18–25 nucleotides in length) that regulate gene expression by targeting protein-coding mRNAs post-transcriptionally. miRNAs have been implicated in cancer development and progression. As miRNAs and their regulatory functions are further revealed, the more the importance of miRNA-directed gene regulation is emphasised. In the human genome, 695 mature miRNAs have been identified, although computational calculation predicts that this may increase to >1000. Deregulation of miRNA expression profiles is thought to be implicated in the pathogenesis of many human cancers including breast tumours. Breast cancer subtypes are observed to have deranged miRNA expression signatures, which makes miRNAs important targets for developing a novel molecular classification of breast cancer and opening avenues for more individualised treatment strategies for patients with breast cancer.

scholarly journals Quantitative Mammographic Density Measurements and Molecular Subtypes in Chinese Women with Breast Cancer

2020 ◽  
Author(s):  
Yuan Tian ◽  
Jennifer L Guida ◽  
Hela Koka ◽  
Er-Ni Li ◽  
Bin Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mammographic Density ◽  
Chinese Women ◽  
Statistical Tests ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

Abstract Background Studies investigating associations between mammographic density (MD) and breast cancer subtypes have generated mixed results. We previously showed that having extremely dense breasts was associated with the HER2-enriched subtype in Chinese breast cancer patients. Methods In this study, we re-evaluated the MD-subtype association in 1,549 Chinese breast cancer patients, using VolparaDensity software to obtain quantitative MD measures. All statistical tests were two-sided. Results Compared to women with luminal A tumors, women with luminal B/HER2- (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.04-1.38, p = 0.01), luminal B/HER2 + (OR = 1.22, 95% CI: 1.03-1.46, p = 0.03), and HER2-enriched tumors (OR = 1.30, 95% CI: 1.06-1.59, p = 0.01) had higher fibroglandular dense volume. These associations were stronger in patients with smaller tumors (&lt;2cm). In contrast, the triple negative subtype was associated with lower non-dense volume (OR = 0.82, 95% CI: 0.68-0.99, p = 0.04), and the association was only seen among older women (&gt;50 years old). Conclusion Although biological mechanisms remain to be investigated, the associations for the HER2-enriched and luminal B subtypes with increasing MD may partially explain the higher prevalence of luminal B and HER2+ breast cancers previously reported in Asian women.

scholarly journals Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

2019 ◽  
Vol 115 (3/4) ◽  
Author(s):  
Kathleen A. Grant ◽  
Ettienne J. Myburgh ◽  
Elizabeth Murray ◽  
Fredrieka M. Pienaar ◽  
Martin Kidd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Early Stage ◽  
Single Gene ◽  
Gene Profiling ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Treatment Groups ◽  
Combined Use ◽  
Microarray Gene

Immunohistochemistry (IHC) is routinely used to approximate breast cancer intrinsic subtypes, which were initially discovered by microarray analysis. However, IHC assessment of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, is a poor surrogate of molecular subtype. Therefore, MammaPrint/BluePrint (MP/BP) microarray gene expression profiling is increasingly used to stratify breast cancer patients into different treatment groups. In this study, ER/PR status, as reported by standard IHC and single-gene mRNA analysis using TargetPrint, was compared with molecular subtyping to evaluate the combined use of MP/BP in South African breast cancer patients. Pathological information of 74 ER/PR positive, HER2 negative tumours from 73 patients who underwent microarray testing, were extracted from a central breast cancer genomics database. The IHC level was standardised by multiplying the intensity score (0–3) by the reported proportion of positively stained nuclei, giving a score of 0–300. Comparison between mRNA levels and IHC determination of ER/PR status demonstrated a significant correlation (pless than 0.001) for both receptors (ER: 0.34 and PR: 0.54). Concordance was shown in 61 (82%) cases and discordance in 13 (18%) of the 74 tumours tested. Further stratification by MP/BP identified 49 (66.2%) Luminal A, 21 (28.4%) Luminal B and 4 (5.4%) Basal-like tumours. Neither IHC nor TargetPrint could substitute BP subtyping, which measures the functional integrity of ER and can identify patients with false-positive tumours who are resistant to hormone therapy. These findings support the implementation of a pathology-supported genetic testing approach combining IHC and microarray gene profiling for definitive prognostic and predictive treatment decision-making in patients with early stage breast cancer. Significance: Single-gene genomic oestrogen and progesterone receptor reporting adds limited additional information to the molecular stratification of breast cancer tumours and does not supersede the immunohistochemistry results. Neither single-gene genomic mRNA nor immunohistochemistry reporting of oestrogen and progesterone receptor status can replace the combined use of MammaPrint/BluePrint genomic molecular subtyping. Reliable distinction between Luminal A and B type tumours is not possible using immunohistochemistry or single-gene genomic mRNA assessment of oestrogen/progesterone and HER2 receptor status. Combining immunohistochemistry and microarray gene profiling enables the identification of endocrine treatment resistant hormone-positive tumours lacking ERα function (Basal-like), despite positive expression at the protein and single-gene RNA level.

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