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 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 Endocrine Therapy in Premenopausal Hormone Receptor–Positive Breast Cancer

2016 ◽  
Vol 12 (11) ◽  
pp. 1148-1156 ◽  
Author(s):  
Amye J. Tevaarwerk ◽  
Kari B. Wisinski ◽  
Ruth M. O’Regan
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Systemic Therapy ◽  
Hormone Receptor ◽  
Randomized Trials ◽  
Early Stage ◽  
Premenopausal Women ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Systemic therapy for premenopausal women with hormone receptor–positive breast cancer has evolved in the last 5 years, but critical questions remain. Recent randomized trials have demonstrated a benefit for the addition of ovarian suppression to endocrine therapy in patients with breast cancers considered to be at high risk for recurrence, whereas those with lower-risk cancers seem to have a favorable outcome with tamoxifen alone. Two large randomized trials have demonstrated a benefit for extending adjuvant tamoxifen beyond 5 years. Currently the choice of systemic therapy is selected empirically but molecular profiling may, in the near future, provide a more conclusive means of selecting an endocrine therapeutic approach for premenopausal patients. Given that a significant subset of hormone receptor–positive cancers are intrinsically resistant to endocrine agents, as well as the finding that inhibiting cyclin-dependent kinases 4 and 6 and mammalian target of rapamycin appears to potentially reverse this resistance in patients with metastatic disease, evaluation of these agents in the early-stage setting is ongoing.

Hormonal Therapy for the Treatment of Postmenopausal Breast Cancer Patients

2008 ◽  
Vol 21 (1) ◽  
pp. 36-45
Author(s):  
Rebecca E. Greene ◽  
Vivian Tsang
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Hormonal Therapy ◽  
Early Stage ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Receptor Modulator

Breast cancer is the most common cancer diagnosed and the second leading cause of cancer-related death in women. The majority of breast cancers diagnosed in postmenopausal women are hormone receptor positive and involve therapy with hormonal agents. Tamoxifen, a selective estrogen-receptor modulator, has been the mainstay of hormonal therapy since the 1970s. The more recent approval and success of aromatase inhibitors, such as anastrozole, letrozole, and exemestane, have seen these agents move to the front line of therapy for postmenopausal women with hormone-positive breast cancer in the adjuvant and metastatic settings. Fulvestrant, a selective estrogen receptor— downregulator, provides an additional hormonal therapy with a novel mechanism of action. This article reviews the current literature available regarding the use of these agents for postmenopausal women with early stage or advanced breast cancer.

Neratinib for the treatment of early-stage, hormone receptor-positive, HER2-overexpressed breast cancer

2020 ◽  
Vol 16 (17) ◽  
pp. 1165-1177
Author(s):  
Yolanda Jerez ◽  
Blanca Herrero ◽  
Marta Arregui ◽  
Blanca Morón ◽  
Miguel Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Future Directions ◽  
Her2 Positive Breast Cancer ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

HER2-positive breast cancer accounts for 18–20% of all breast cancers. Despite significant advances and the currently available adjuvant treatments for management of the disease, approximately 25% of HER2-positive early-stage breast cancer patients show relapse and die. Neratinib is an irreversible tyrosine kinase inhibitor. Multiple studies have reported its significant antitumor activity in metastatic HER2-positive breast cancer. It is administered orally and has also been tested in the adjuvant setting. In this article, we present a comprehensive review of the pharmacokinetics and pharmacodynamics of neratinib as well as its clinical efficacy, with an emphasis on early HER2-positive breast cancer and suggestions for future directions for neratinib research.

scholarly journals Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women

2009 ◽  
Vol 1 ◽  
pp. CMT.S9 ◽  
Author(s):  
Monica Milani ◽  
Gautam Jha ◽  
David A. Potter
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Estrogen Receptor ◽  
Hormone Receptor ◽  
Early Stage ◽  
Breast Cancers ◽  
Adjuvant Setting ◽  
Hormone Receptor Positive ◽  
Menopausal Women ◽  
Post Menopausal

The majority of breast cancers express the estrogen receptor and depend on estradiol (E2) for their growth. Hormonal therapy aims at depriving estrogen signaling either by using selective estrogen receptor modulators (SERM)–-that interfere with the binding of E2 to its receptor (ER)–-or aromatase inhibitors (AI)–-that block the aromatase-dependent synthesis of E2. While SERMs are recommended for both pre- and post-menopausal patients, AIs are indicated only for post-menopausal patients. For the past 20 years, the SERM tamoxifen has been considered the “gold standard” for the treatment of hormone receptor positive breast cancers. However, tamoxifen's role is now challenged by third generation AIs, such as anastrozole, which exhibit greater efficacy in the adjuvant setting in several recently reported trials. This review will focus on anastrozole's mechanism of action, dosing, pharmacology, pharmacokinetics, and clinical applications. It will briefly discuss the clinical trials that determined anastrozole's efficacy in the treatment of advanced breast cancer (ABC) and in the neo-adjuvant setting. Finally, it will present the clinical trials that established anastrozole as a frontline agent in the treatment of post-menopausal women with hormone receptor positive early breast cancer.

A new digital classification schema to detect treatment variances and enable value-based payment reforms.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 28-28
Author(s):  
Andrew Pecora ◽  
Eric V Schultz ◽  
Kelly Choi ◽  
William Kea ◽  
Augie Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Performance Status ◽  
Treatment Strategies ◽  
Community Setting ◽  
Cost Ratio ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Episodes Of Care

28 Background: Value based payment reforms which improve the outcome to cost ratio (paying for outcomes not for services) require detailed information on both elements. Although the digitalization of medicine via the EHR may facilitate data collection, the imprecise ICD9 and ICD10 schemas hinder analysis (eg: all breast cancers are ICD9 174.9). A more precise classification schema that accounts for biologic variances to allow analysis (and reduction) of treatment variances is needed. Methods: We have developed a digital classification (COTA Nodal Address) based on known clinically relevant prognostic variables. (eg: breast cancer variables include stage, tumor size, hormone status, her2 neu status, etc.). The digital classification also accounts for therapy status (neoadjuvant vs adjuvant, etc.) and line (1st or 2nd treatment, etc.). Results: Using breast cancer as an example, there are > 2975 unique CNA phenotypes that encompass prognostic and treatment status variables. However, in a series of 1204 patients in a community setting only 114 CNAs have been utilized, suggesting biologic disequilibrium. Two phenotypes accounted for the top 25% of cases, 6 for the top 50% and 16 for the top 75%. Early stage, small tumor, hormone receptor positive were most common. The CNA classification uncovered treatment variances among patients with similar phenotypes. In an ongoing episodes of care payment program, young breast cancer patients with early stage, good performance status, hormone positive, her2 neu negative, very small tumors (with similar extended attributes) received varying adjuvant treatment strategies (hormone alone 46% , non-anthracycline 35%, anthracycline chemotherapy 4%, observation 1%). Conclusions: Unlike ICD9/10 systems, a digital classification schema that precisely segregates cancers into unique cohorts based on complete biologic characteristics can rapidly identify behavioral variances at scale that drive differences in outcomes and costs. Using the breast cancer model, we have noted demographic disequilibrium in cancer presentations (potentially a factor of both biology and screening practices) and major variances in treatment strategies (with impact on outcomes/ costs).

scholarly journals Deep learning from HE slides to predict the clinical benefit from adjuvant chemotherapy in hormone receptor-positive breast cancer

2020 ◽  
Author(s):  
Soo Youn Cho ◽  
Jeong Hoon Lee ◽  
Jai Min Ryu ◽  
Jeong Eon Lee ◽  
Eun Yoon Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Early Stage ◽  
Oncotype Dx ◽  
Hormone Receptor Positive ◽  
Gene Assay ◽  
Positive Breast Cancer

Abstract Background: The predictive value of adjuvant chemotherapy for early-stage hormone receptor-positive breast cancer has been only validated by a 21-gene expression assay. We hypothesized that deep-learning prediction from HE images, called Lunit-SCOPE, is a potential prognostic and predictive biomarker of adjuvant chemotherapy.Methods: We retrospectively collected HE slides from 1153 de-identified breast cancer patients at the Samsung Medical Center (SMC) in order to develop a deep-learning algorithm called Lunit-SCOPE. The histological parameters from 255 patients, deciphered by Lunit-SCOPE, were trained to predict the recurrence score (RS) using the 21-gene assay from Oncotype DX. We validated the model’s performance using the recurrence survival of 898 patients and The Cancer Genome Atlas (TCGA) cohort, and examined related biological functions through RNA sequence data.Results: The histologic parameter-based RS prediction model predicted the oncotype DX score (R2=0.96) and the recurrence survival analysis on the validation (p<0.01) and TCGA cohort (p<0.01), where the most important variables were the nuclear grade and the mitotic cells in the cancer epithelium. Of the 85 patients classified as the high-risk group, 72 patients who received adjuvant therapy had a significantly better survival (p<0.01). The functions of the top 300 highly correlated genes with a predicted RS were enriched for cell cycle, nuclear division and cell division. Of the 21-genes from the Oncotype DX, the predicted RS had positive correlations with the proliferation category genes and was negatively correlated with the prognostic genes in the estrogen category.Conclusion: An integrative analysis using Lunit-SCOPE predicts a high risk of recurrence and those who would benefit from adjuvant chemotherapy for early-stage hormone-positive breast cancer.

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

Sign in / Sign up

Export Citation Format

Share Document