scholarly journals Practical consensus recommendations on management of HR + ve early breast cancer with specific reference to genomic profiling

2018 ◽  
Vol 07 (02) ◽  
pp. 096-101 ◽  
Author(s):  
A. Aggarwal ◽  
A. Vaid ◽  
A. Ramesh ◽  
Purvish M. Parikh ◽  
S. Purohit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Early Breast Cancer ◽  
Early Stage ◽  
Practical Experience ◽  
Specific Reference ◽  
Chemotherapy Response ◽  
Breast Cancers ◽  
Early Stage Disease ◽  
Consensus Recommendations

AbstractBreast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

scholarly journals Practical consensus recommendations on ovarian suppression in early breast cancer (adjuvant)

2018 ◽  
Vol 07 (02) ◽  
pp. 151-155
Author(s):  
M. Singhal ◽  
T. P. Sahoo ◽  
S. Aggarwal ◽  
A. Singhvi ◽  
V. Kaushal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Early Stage ◽  
Practical Experience ◽  
Expert Group ◽  
Ovarian Suppression ◽  
Consensus Recommendations ◽  
New Treatment ◽  
Single Modality

AbstractSubstantial survival benefits exist for patients with early-stage breast cancer who undergo treatment with single-modality ovarian suppression, but its value is uncertain. Expert oncologist discussed to determine whether additional benefits exist with ovarian suppression plus multiple adjuvant therapy which provides a new treatment option that reduces the risk of recurrence in early breast cancer. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

2021 ◽  
Vol 27 (8) ◽  
pp. 2148-2158
Author(s):  
Karolina Edlund ◽  
Katrin Madjar ◽  
Antje Lebrecht ◽  
Bahriye Aktas ◽  
Henryk Pilch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Chemotherapy Response

scholarly journals Practical consensus recommendations regarding the management of HER2 neu positive early breast cancer

2018 ◽  
Vol 07 (02) ◽  
pp. 102-105
Author(s):  
A. Bahl ◽  
R. Singh ◽  
J. Wadhwa ◽  
S. Gupta ◽  
M. Ahmed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Cancer Mortality ◽  
Breast Cancer Mortality ◽  
Practical Experience ◽  
Expert Group ◽  
Over Expression ◽  
Large Group ◽  
Consensus Recommendations ◽  
Prognostic Feature

AbstractOver-expression of HER2 is generally considered to be a negative prognostic feature because it accompanies an increase in breast cancer mortality. However, the development of agents that specifically target HER2 has improved the management of patients with these tumours. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations with regards to the use of these agents and the management of HER2 neu early breast cancer for the benefit of community oncologists.

scholarly journals Prospective Validation of a Genomic Assay in Breast Cancer: The 70-gene MammaPrint Assay and the MINDACT Trial

2019 ◽  
Vol 48 (1) ◽  
pp. 18
Author(s):  
William Audeh ◽  
Lisa Blumencranz ◽  
Heather Kling ◽  
Harsha Trivedi ◽  
Gordan Srkalovic
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
High Risk ◽  
Expression Analysis ◽  
Clinical Utility ◽  
Gene Expression Analysis ◽  
Early Stage ◽  
Significant Proportion ◽  
Breast Cancers ◽  
Gene Assay

<p>MammaPrint was the first genomic assay in breast cancer to be validated with a prospective randomized trial, the MINDACT trial. The 70 gene MammaPrint assay was developed to determine the risk of distant metastasis in early stage breast cancer through gene expression analysis and was the first FDA cleared genomic assay for breast cancer. The assay identifies primary breast cancers likely to metastasize within the first five years of diagnosis and has clinical utility for helping to determine the expected benefit from adjuvant chemotherapy. The MINDACT Trial was the first trial of a genomic assay in breast cancer to provide prospective, randomized evidence of clinical utility for this important clinical question, identifying a significant proportion of patients who could safely forgo chemotherapy within a cohort of patients with high risk clinical characteristics. Nearly half of all patients (46%) who would have been advised chemotherapy according to clinical guidelines were identified genomically by MammaPrint as being low risk and found to have equivalent rates of freedom from metastasis at 5 years with or without chemotherapy. Based upon the MINDACT trial, the ASCO Biomarker Guidelines now approve the use of MammaPrint to inform decisions regarding chemotherapy for women with clinically high-risk ER+ breast cancer, and as the only approved assay for use in women with 1-3 involved lymph nodes. Recent studies suggest information obtained from the 70-gene assay may also help inform decisions regarding endocrine therapy, as well as chemotherapy, targeted therapy and immunotherapy.</p><p><strong>Conclusion. </strong>The power of gene expression analysis in breast cancer, effectively illustrated with MammaPrint in the MINDACT trial, is now being explored through examination of the full transcriptome in breast cancer.</p>

Retrospective analysis of phosphorylation status of the estrogen receptor in patients with early stage disease

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21034-21034 ◽  
Author(s):  
R. F. Swaby ◽  
M. Huang ◽  
K. J. Ruth ◽  
E. A. Ross ◽  
Y. Gong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Early Breast Cancer ◽  
Nuclear Accumulation ◽  
Type I ◽  
Breast Cancers ◽  
Early Stage Disease ◽  
Akt Activation ◽  
Cancer Pathogenesis

21034 Background: The AKT kinase, when phosphorylated to its activated form (pAKT), mediates many proliferative and survival effects of growth factor receptors such as members of the epidermal growth factor receptor (EGFR) family. Overexpression of AKT in breast neoplasms suggests that AKT activation is involved in breast cancer development and/or progression, and contributes to poor outcome. pAKT is frequently upregulated in Her-2/neu positive breast cancers. Activated AKT is able to phosphorylate in vitro serine 167 (pS167) of estrogen receptor alpha (ERa), resulting in ER-mediated transcriptional activity in the absence of estrogen and possibly contributing to tamoxifen resistance in ERa positive breast cancers. In addition, ERa is phosphorylated at S118 (pS118) by MAPK. Thus, it is possible that pAKT- mediated ERa phosphorylation is implicated in tumorigenesis and resistance to treatment with hormonal therapy in patients with breast cancer. Methods: Utilizing commercially available antibodies, IHC analysis of 125 paraffin-embedded, ERa positive, early breast cancer cases, stratified for stage, were tested for pAKT, PTEN, pS167, and pS118. Staining intensity and number of positive cells were assessed by 4 independent graders. Fisher's exact test was used to determine the significance of associations with a two-sided type I error of 5%. Results: Phosphorylation of AKT occurred in approximately one-half of cases. pS167 was phosphorylated in 66% of pAKT positive cases compared to 35% of pAKT negative cases (p<0.0001). When we analyzed nuclear pAKT staining, this association was more pronounced: 76% of pAKT(+) vs. 37% of pAKT(-) (p<0.0001). 69% of pS118(+) cases were pS167(+) compared to only 15% pS167(+) when pS118 was negative (p<0.0001). In approx. 32% of cases pAKT was present in both the cytoplasm and nucleus. 20% of samples had only cytoplasmic pAKT, while in 4% of cases pAKT was nuclear only, supporting the hypothesis that cytoplasmic phosphorylation of AKT may precede nuclear accumulation. Conclusions: Phosphorylation of pS167ERa is significantly associated with AKT activation (especially in the nucleus) in early breast cancer, supporting the hypothesis that these two events may be causally linked and contribute to breast cancer pathogenesis. No significant financial relationships to disclose.

scholarly journals Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer

2021 ◽  
Author(s):  
Eileen E. Parkes ◽  
Kienan I. Savage ◽  
Tong Lioe ◽  
Clinton Boyd ◽  
Sophia Halliday ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Response ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Feasibility Study ◽  
Gene Expression Signature ◽  
Response To Treatment ◽  
Chemotherapy Response ◽  
Response To Neoadjuvant Chemotherapy

Abstract Background The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer. Methods This feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /−taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures. Results DDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13–15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression. Conclusions This study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, “cold” tumours may be effective for immune priming. Trial registration Not applicable (non-interventional study). CRUK Internal Database Number 14232.

scholarly journals Practical consensus recommendations regarding the management of hormone receptor positive early breast cancer in elderly women

2018 ◽  
Vol 07 (02) ◽  
pp. 123-126
Author(s):  
Govind Babu ◽  
A. Goel ◽  
S. Agarwal ◽  
S. Gupta ◽  
P. Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cause Of Death ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Older Patients ◽  
Elderly Women ◽  
Practical Experience ◽  
Expert Group ◽  
Consensus Recommendations ◽  
Hormone Receptor Positive

AbstractBreast cancer is a leading cause of death among women, and its incidence increases with age. Currently the treatment of breast cancer in older patients is almost identical to their younger counterparts. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations for the benefit of community oncologists regarding the management of early breast cancer specifically in elderly women.

scholarly journals Prognostic Significance of Tissue Inhibitor of Metalloproteinase-1 in Breast Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Arunee Dechaphunkul ◽  
Monlika Phukaoloun ◽  
Kanet Kanjanapradit ◽  
Kathryn Graham ◽  
Sunita Ghosh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Prognostic Significance ◽  
Early Recurrence ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Breast Cancers ◽  
Tissue Inhibitor ◽  
Early Stage Disease ◽  
Rna Levels

Introduction. Despite advances in breast cancer systemic treatment, new prognostic and predictive factors are still needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic significance of TIMP-1 in breast cancer.Methods. A single center-based case-control study was applied. Primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1.Results. At the optimized cut-point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.64 (P=0.04), but without significant differences in overall survival (HR 1.29,P=0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0,P=0.92), there was a tendency for short overall survival in patients with high expression (HR 1.41,P=0.21).Conclusions. Our data indicate that elevated TIMP-1 RNA levels are independently prognostic for early recurrence, and there is a tendency for association of high cytoplasmic TIMP-1 protein levels with short survival in primary breast cancer.

Gene Expression Assay in the Management of Early Breast Cancer

2020 ◽  
Vol 27 (17) ◽  
pp. 2826-2839 ◽  
Author(s):  
Roberta Caputo ◽  
Daniela Cianniello ◽  
Antonio Giordano ◽  
Michela Piezzo ◽  
Maria Riemma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Decision Making ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Treatment Decision ◽  
Endocrine Treatment ◽  
Expression Ratio ◽  
Treatment Decision Making ◽  
Low Sensitivity

The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician’s decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).

scholarly journals Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xu Yang ◽  
Geng-Xi Cai ◽  
Bo-Wei Han ◽  
Zhi-Wei Guo ◽  
Ying-Song Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cell Receptor ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Plasma Dna ◽  
Transcription Start Sites ◽  
Response To Chemotherapy

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

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