TEST:

EndoPredict®

Integrating CR with the Ki-67 index improves prognostic accuracy and provides a cost-effective alternative to the EP test for luminal-type early breast cancer.

Moreover, the implementation of Molecular Tumor Boards further enhances personalized treatment strategies, contributing to improved patient outcomes and survival rates. This review underscores the significance of tailored therapeutic approaches and highlights the dynamic evolution of breast cancer in clinical practice.

While multiple gene expression profiling tests are available, they classify patients differently and are not interchangeable; therefore, their application should be at the clinician's discretion during the decision-making process. It is essential that these tests are not the sole factor in determining the best treatment plan: other clinical considerations and patient preferences should also play a significant role in guiding treatment decisions.

P2, N=1100, Recruiting, SOLTI Breast Cancer Research Group | Trial completion date: Jul 2030 --> Dec 2031 | Trial primary completion date: Aug 2028 --> Oct 2029

All four tests have prognostic ability in LN+ patients. Evidence on predictive benefit is weaker, with equivocal evidence that Oncotype DX may predict chemotherapy benefit in LN+ post-menopausal patients. Use of Oncotype DX leads to fewer patients being recommended chemotherapy.

This study presents, for the first time, the development of a clinically accessible nomogram designed to estimate the probability of obtaining a high-risk result in the EndoPredict® assay. The use of easily available clinicopathological features allows for the optimization of patient selection for the EndoPredict® assay, ensuring that those who would most benefit from undergoing the test are identified.

The clinical behavior of HER2-enriched cancers is dominated by the underlying ER subtype. ER+/HER2-enriched cancers tend to have more indolent course and lesser chemotherapy sensitivity than their ER counterparts.

P2, N=70, Recruiting, Criterium, Inc. | N=100 --> 70 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2027

The study advocates for the integration of genomic tools, particularly the EndoPredict test, in the management of breast cancer in Mexican women for enhanced precision in treatment decisions. Our findings contribute valuable insights to the evolving landscape of breast cancer diagnosis and management in the Mexican population.

The EndoPredict-Dx score accurately predicted the likelihood of infective endocarditis using clinical and laboratory data collected at admission.

Hormonal therapy consisted of letrozole for post-menopausal patients and tamoxifen plus LH-RH agonist for pre/peri-menopausal patients. Neoadjuvant endocrine therapy for 16 weeks changes subtype classification by PAM50 from luminal B to luminal A and the ROR drastically. Greater effects were noted for the combination, not statistically significant, but this warrants further investigation in a larger cohort. There were 3 HER2-enriched cases with poor response, but this was not significant because of the small sample size.

Objective: By analyzing baseline and follow up data from RESCUE, we describe the current (neo)adjuvant treatment landscape for pt with ER+ HER2neg early-stage breast cancer including: type of endocrine agents used, addition of GnRH analogs (GnRHAa)/ovarian function suppression (OFS) to ET in premenopausal pt, use of chemotherapy and use of bone modifying agents (Bisphoshonates or Denosumab) in the adjuvant setting...In these 57 pt, GnRHa/OFS was recommended to be combined with an aromatase inhibitor as initial ET in 15 cases (3,8% of premenopausal pt) and with tamoxifen in 41 cases (10,4% of premenopausal pt)... These real world data show that in spite of existing guideline recommendations for the use of GnRHa/OFS in premenopausal women with early luminal breast cancer at higher risk for relapse, this is not routinely implemented. Therefore, regarding the ET recommendation, this patient cohort might be undertreated. Follow up data on actually received ET (including +/- GnRH) and CTX (including +/- anthracyclines) will be presented in detail.

Consequently, those tests cannot be employed interchangeably. The results emphasize the pressing necessity for further comparative analysis of multi-genomic tests to prevent misclassification of risk class and disease recurrence risk in breast cancer patients.

P2; N=100; Not yet recruiting; Sponsor:Peking University

Total 42 patients. Mean age 58.3 years, 71.4% post-menopausal. Breast conservation was done 47.6%.

This paper reviews evidence for several genomic tests, including Oncotype DX, MammaPrint, Breast Cancer Index, RucurIndex, and EndoPredict, which assist in tailoring adjuvant therapy. Additionally, we explore the role of liquid biopsies in personalizing treatment, emphasizing the importance of considering late relapse risks and potential benefits of extended systemic therapy for HR+/HER2- breast cancer patients.

In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

"Eurobio Scientific...announces the finalisation of its agreement with Myriad Genetics to acquire the EndoPredict genomic test. As part of the agreement announced on 7 May 2024...on 1 August 2024 the Group has completed the acquisition of the second-generation genomic test EndoPredict for breast cancer and the license agreement to distribute the second-generation genomic test Prolaris for prostate cancer from Myriad Genetics. Revenues from these two activities are around €8m on an annual basis, with EBITDA levels in the short and medium term diluting the Group's performance."

Chemotherapy was indicated for those who would not receive it before. It was contraindicated in patients who would previously undergo chemotherapy.

Sponsored by Myriad Genetics

Sponsored by Myriad Genetics

When 0-1 MGA was defined as low-risk and 2-4 MGA as high-risk, the 5-year DRFS was 97.4% for low-risk and 75.5% for high-risk (n=248, n=182, respectively; p=5.5e-11), which was a better prognostic prediction performance than any MGA alone. Discussion By performing Curebest and obtaining microarray data, it was possible to obtain the results of multiple MGAs, and it was suggested that combining each of them may enable more accurate prediction of recurrence

This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.

Among these tests, Prosigna and EndoPredict® have at present been validated only on a prognostic level, while Oncotype Dx, MammaPrint, and BCI hold both a prognostic and predictive role. Oncologists and pathologists engaged in the management of EBC will find in this review a thorough comparison of available genomic assays, as well as strategies to optimize the utilization of the information derived from them.

In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.

P2; Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

"The UK National Institute for Health and Care Excellence (NICE)...recommended three prognostic gene expression tests as tools for guiding adjuvant chemotherapy treatment decisions in an expanded population of early breast cancer patients...In a final guidance, NICE said Myriad Genetics' EndoPredict (which is being sold to Eurobio), Veracyte's Prosigna, and Exact Sciences' Oncotype DX can be used within the National Health Service (NHS) to guide adjuvant treatment for postmenopausal women or men with estrogen receptor-positive, HER2-negative early breast cancer and one to three positive lymph nodes."

"Myriad Genetics, Inc...announced the reorganization of its European operations to better align company resources to its domestic opportunities while continuing to serve key biopharma partners and patients outside the United States."

EndoPredict can guide decisions on adjuvant chemotherapy in early luminal breast cancer. EndoPredict risk stratification is also applicable in premenopausal women.

The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

Furthermore, through attention analysis, we demonstrated the biological significance and clinical relevance of these subpathways in predicting patient outcomes. The source code is available at http://biohealth.snu.ac.kr/software/ExplainableMLKGNN.

Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low risk patients are reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

Our preliminary results suggest that gene expression profiling holds more weight than nodal status in determining adjuvant therapy. Our study is limited by sample size, and data collection is still ongoing. Premenopausal patients were included for the purpose of this report, but ultimately will be evaluated separately from postmenopausal patients, as in other similar studies.

EP using microarray data from FF tissues was useful in predicting distant recurrence risk in luminal breast cancer, and EP might be utilized in microarray data from FFPE tissues.

Pre-treatment tumor FOXC1 mRNA (on qRTPCR) or protein expression (on IHC) + TS + TG presents a uniquely economical alternative solution to multimarker tests like OncotypeDx, Mammaprint or Endopredict, for guiding therapy of patients diagnosed with ER+LN- breast cancer.

Validation of these biomarkers as reliable surrogate endpoints can also lead to a revolution in the clinical trial designs, and potentially avoid the need for repeated tissue biopsies in the surveillance of disease response. Further validation and guidelines for biomarker use will be instrumental in helping standardize the use of NET.

ctDNA+ patients underwent systemic staging with imaging and randomized to continuation of adjuvant therapy versus switching to fulvestrant plus palbociclib if there was no evidence of distant metastatic disease. ctDNA surveillance of ER+/HER2- breast cancers during adjuvant endocrine therapy indicate 8.3% detection rate at patient level and 3.4% at assay level. Serial screening increases detection rates as 23% of positive ctDNA tests occurred after an initial negative result. 83% of ctDNA+ patients had true molecular relapse without imaging detectable metastatic disease.

P2; Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

ENDOPREDICT PROVED TO BE AN EFFECTIVE THERAPEUTIC DECISION TOOL, WITH FAVORABLE PROGNOSTIC POWER IN WOMEN WITH BREAST CANCER TREATED WITH HORMONOTHERAPY ALONE.

P=N/A; Active, not recruiting --> Completed

Pre-treatment tumor FOXC1 mRNA or protein expression (assessed using qRT-PCR or routine immunohistochemistry (IHC), respectively, when combined with TS and TG presents a unique and economical alternative solution to multimarker gene panel tests like OncotypeDx®, Mammaprint® or Endopredict®, for guiding therapy of patients diagnosed with ER+LN- breast cancer in resource challenged settings. Such an approach to identify elevated risk of recurrence in patients diagnosed with ER+LN- breast cancer and prevent the same by guiding adjuvant endocrine + chemotherapy decisions, could help to extend recurrence-free and overall survival. Such an approach merits testing in real world ER+LN- patient cohorts in resource-challenged settings to help support implementation of this FOXC1-driven predictive biomarker strategy in the clinic.

In comparison to IDC, the variants of ILC with favorable prognosis show lower rates of high-risk results in MGT, while the variants of ILC with poor prognosis do not differ significantly from IDC. For patients who diagnosed the variants of ILC with poor prognosis, MGT could be useful for prognosis prediction or treatment decision-making.