TEST:

EndoPredict®

No abstract available

P2, N=100, Not yet recruiting, 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.

Unfavorable subtypes have shown a significantly higher-risk result of MGT, and patients with unfavorable types of breast cancer and high-risk MGT results have exhibited the worst prognosis. Consequently, we can suggest that MGT can be used as a prognosis evaluation tool for certain special subtypes of breast cancer and further utilized to aid in treatment decisions.

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.

Conclusion These results support the use of multigene assays to guide treatment decisions in node-negative HR+/HER2- early-stage breast cancer to improve treatment outcomes, and also result in substantial net cost savings from a societal perspective. The prediction of chemotherapy benefit using the Oncotype DX test resulted in substantially higher cost savings and improved breast cancer outcomes.

We identified 4 biologically driven HR+, HER2- ILC groups describing tumor microenvironment heterogeneity. Of note, two of the three groups associated to worse disease outcome were related to metabolism, highlighting the importance of such process in ILC biology and in the future development of new treatment strategies. Moreover, the prognostic power of our index has the potential to refine the assessment of the risk of relapse in ILC.

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.

The development and validation process of each tool was also briefly introduced. It is expected that the consensus will help guide and standardize the clinical use of multigene testing tools and further improve the level of precise treatment for EBC.

P2; N=530 --> 1100 | Trial primary completion date: Feb 2030 --> Aug 2028

704 of 938 pts enrolled between 10/2020 and 09/2022 had ≥6 months follow-up, and 624 pts were evaluable for analysis. Median age was 68 years, 92% were postmenopausal, and 39% presented with de novo ABC whereas 61% had relapse from EBC. Gene expression tests at ID, to predict benefit of adjuvant chemotherapy have been performed in just 3% (Oncotype DX in 50%, Endopredict in 44% and Mammaprint in 6%, respectively).

Even after 5 years of adjuvant endocrine therapy, patients with hormone receptor-positive breast cancer have a significant risk for late recurrence, including distant metastases, that might be prevented with longer durations of endocrine therapy. However, the added toxicity and variable benefit derived from extended endocrine therapy make optimal patient selection crucial. Genomic assays are in development to risk-stratify patients for late recurrence and determine efficacy of extended endocrine therapy, with the aim to help guide extended endocrine therapy decisions for clinicians and individualize treatment strategies for patients.

Ki67 and tumor size seem to be the only significant predictors of high-risk EndoPredict®. The nomogram based on our data provided a graphical representation of the predicted probability of the need for chemotherapy and could be used as an additional tool to aid in clinical decision-making.

P2; Recruiting --> Active, not recruiting

In these cases, favorable clinicopathological features often modify the EPClin index. Here, the Ki67 index is a more reliable marker of the genomic profile.

The establishment of criteria used to perform molecular tests in BC patients needs to be standardized, and the tests should be performed in specialized laboratories. Test centralization and reimbursement are fundamental to be able to compare the outcome of patients treated or not with chemotherapy in addition to hormone therapy to verify data from clinical randomized studies in a real-world setting.