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>

scholarly journals Gene Expression Assays for Early-Stage Hormone Receptor–Positive Breast Cancer: Understanding the Differences

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Ana Tablante Nunes ◽  
Deborah E Collyar ◽  
Lyndsay N Harris
Keyword(s):  
Breast Cancer ◽  
Clinical Utility ◽  
Early Stage ◽  
Breast Cancers ◽  
Level Of Evidence ◽  
Hormone Receptor Positive ◽  
Gene Assay ◽  
Show Evidence ◽  
American Society ◽  
Development And Validation

Abstract Biomarkers are frequently used to guide decisions for treatment of early-stage estrogen (ER) and progesterone (PR) receptor–positive (ER/PR+) invasive breast cancers and have been incorporated into guidelines. The American Society of Clinical Oncology (ASCO) 2016 guideline and a 2017 update were recently published to help clinicians use the tests available. ASCO currently recommends five tests that show evidence of clinical utility based on the parameters defined in the guideline. These include the 21-gene assay (Oncotype DX), Prediction of Analysis of Microarray-50 (PAM50), 12-gene risk score (Endopredict), Breast Cancer Index (BCI), and, most recently, the 70-gene assay (Mammaprint). However, discordance is often seen when the results of these gene assays are compared in a particular patient, for a number of reasons: the assays were initially developed to answer different questions, and the molecular makeup of each signature reflects this; the patient populations that were studied also differed and may not reflect the patient being tested; furthermore, the study design and statistical analysis varied between each test, leading to different scoring scales that may not be comparable. In this review, the background on the development and validation of these assays is discussed, and studies comparing them are reviewed. To provide guidance on which test to choose, the studies that support the level of evidence for clinical utility are presented. However, the choice of a particular test will also be influenced by socioeconomic factors, clinical factors, and patient preferences. We hope that a better understanding of the scientific and clinical rationale for each test will allow patients and providers to make optimal decisions for treatment of early-stage ER/PR+ breast cancer.

scholarly journals An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Erica M. Stringer-Reasor ◽  
Jori E. May ◽  
Eva Olariu ◽  
Valerie Caterinicchia ◽  
Yufeng Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Repair ◽  
Pilot Study ◽  
Expression Analysis ◽  
Triple Negative Breast Cancer ◽  
Gene Expression Analysis ◽  
Triple Negative ◽  
Egfr Inhibition ◽  
Link Type

Abstract Background Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Methods A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. Results Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. Trial registration ClinicalTrials.gov, NCT02158507. Registered on 12 September 2014

scholarly journals 10P The clinical actionability of PTEN protein and gene expression analysis in HR- and HER2+ breast cancers

2021 ◽  
Vol 32 ◽  
pp. S25
Author(s):  
N. Fusco ◽  
E. Sajjadi ◽  
K. Venetis ◽  
M. Invernizzi ◽  
D. Gambini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Breast Cancers ◽  
Pten Protein

Gene expression analysis of invasive breast carcinoma yields differential patterns in luminal subtypes of breast cancer

2021 ◽  
pp. 151814
Author(s):  
Ahmed S. Abdelhafiz ◽  
Merhan A. Fouda ◽  
Nahla A. Elzefzafy ◽  
Iman I. Taha ◽  
Omar M. Mohemmed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Carcinoma ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Invasive Breast Carcinoma

scholarly journals Gene expression analysis supports tumor threshold over 2.0 cm for T-category breast cancer

2016 ◽  
Vol 2016 (1) ◽  
Author(s):  
Hiroko K. Solvang ◽  
Arnoldo Frigessi ◽  
Fateme Kaveh ◽  
Margit L. H. Riis ◽  
Torben Lüders ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
T Category

scholarly journals Role of CD4+ CD25+ FOXP3+ regulatory T-cells and human papilloma virus infection in Egyptian Women with breast cancer

2019 ◽  
Author(s):  
Amany Tawfeik ◽  
Ahmed Mora ◽  
Ahmed Osman ◽  
Nabila Elsheikh ◽  
Mohamed Elrefaei
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
High Risk ◽  
Human Papilloma Virus ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Early Stage ◽  
Significant Proportion ◽  
Papilloma Virus ◽  
Egyptian Women

Abstract Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment and blood of breast cancer (BC) patients and may play a key role in the progression of BC. High-risk human papilloma virus (HPV) have a causal role in a significant proportion of cervical, and head, and neck tumors and may play an important role in evoking neoplasia in BC. In this study we assessed the prevalence of CD4+Tregs (CD4+CD25+ FOXP3+ cells) and CD8+T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL) and 20 healthy volunteers (HV). High-risk HPV genotype type 16, 18, and 31 was investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HPV was detected in 4 BC, but in none of BBL patients. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, (p < 0.001). In addition, we observed a significantly higher frequency of CD8+ T cells in peripheral blood of patients with late stage III compared to early stage I and II BC (p = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). In conclusion, CD4+ Tregs may contribute to progression BC in Egyptian women with HPV infection. The potential role CD4+ Tregs as a prognostic or predictive parameter should be analyzed in a larger longitudinal study with sufficient follow-up time.

scholarly journals Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Toshiaki Iwase ◽  
Kenichi Harano ◽  
Hiroko Masuda ◽  
Kumiko Kida ◽  
Kenneth R. Hess ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Analysis ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Gene Expression Analysis
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