TEST:

EndoPredict®

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.

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.

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.

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.

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.

P=N/A; Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Mar 2023 --> Sep 2023

No abstracts available

The second interim analysis shows that risk assessments and genetic testing are rarely performed at ID in clinical routine in Germany and Austria.

The TEAM pathology study consists of 3284 postmenopausal hormone positive breast cancer patients treated with either exemestane or tamoxifen followed by exemestane. Other clinico-pathologic tools such as Influence 2.0 and CTS-5 have good prognostic ability when compared to Oncotype Dx-trained results and RSClin. >

In this paper, we reviewed the 5 most widely used and studied genomic panel technologies in breast cancer, namely Oncotype DX, MammaPrint, RecurIndex, PAM50, and EndoPredict, according to accessibility and availability. Based on the results of the completed or ongoing clinical studies, we summarized the origin, applicable population, and clinical efficacy of each detection method, and discussed the potential development prospect of detection technology in the future.

By contrast, our results in patients ≥70 are equivocal and suggest that GES should be used with caution in this population. Further development and validation may be needed in this particular setting.

Conclusions This study emphasizes that most drugs are given at fixed dose and the gap in knowledge we have on the efficacy of the novel anti-cancer treatments and the use of GEP and MS according to patient adiposity. As the prevalence of obesity is increasing worldwide, the evaluation of body composition is needed to increase knowledge on optimal use of drugs in clinical practice.

Conclusions Our analysis provides the first vulnerability prediction frame of genomic risk patients assessed by routinely used GES. This underlines the need of caution in interpreting the results of active clinical trials recruiting patients according to genomic risk for the assessment of novel anti-cancer drugs in HR+/HER2- eBC such as NATALEE trial.

P2 | N=100 | Recruiting | Sponsor: Criterium, Inc. | Trial primary completion date: Dec 2022 ➔ Dec 2023

P3; Active, not recruiting --> Completed

Addition of GRSs to PREDICT had limited impact on model fit or treatment received. This analysis does not support widespread adoption of current GRSs based on our implementations of commercial products.

P=N/A; Trial completion date: Mar 2023 --> Jun 2023 | Trial primary completion date: Dec 2022 --> Mar 2023

github.com/UEFBiomedicalInformaticsLab/OnlineLearningBD. Supplementary data are available at Bioinformatics Advances online.

With a median follow-up of 54.1 months (range 8.2-76.6), the 5-year disease-free survival rates of low- and high-risk groups were 100% and 88.9%, respectively (p < 0.001). The EPclin score was associated with recurrences in ER+/HER2- early breast cancer.

Preliminary inter-observer analysis showed a good concordance (≥90%) for IHC4+C scoring on local and central IHC, supporting its technical validity for a real-life use.

Prospective studies on ILC with genomic assays are warranted given the various subtypes of and treatment options for this underestimated, but frequently occurring cancer. Genomic assays can be employed in ILC patients to predict the risk of recurrence and identify those patients who might benefit from chemotherapy in addition to their standard treatment regimen.

"Myriad Genetics...announced multiple presentations of new data at the 2022 San Antonio Breast Cancer Symposium (SABCS), including a spotlight discussion on breast cancer risk prediction....Spotlight discussion highlights how combined risk score may lead to improved breast cancer prevention and screening strategies....Additionally, there will also be poster session (P6-01-24) about an independent EndoPredict study....The study looked at prospective long-term outcome data with EndoPredict for women with early-stage breast cancer."

P=N/A; Active, not recruiting --> Completed | Trial completion date: Oct 2022 --> May 2022 | Trial primary completion date: Sep 2022 --> May 2022

P=N/A | N=2780 | Active, not recruiting | Sponsor: Tata Memorial Centre | Trial completion date: Jul 2022 --> Dec 2022

Several prospective and retrospective studies have investigated the correlation between gene expression risk score from core needle biopsy before neoadjuvant therapy and the likelihood of 1) clinical and pathological response to neoadjuvant chemotherapy and endocrine therapy, 2) conservative surgery after neoadjuvant chemotherapy and endocrine therapy, and 3) survival following neoadjuvant chemotherapy and endocrine therapy. The purpose of this review is to provide an overview of the potential clinical utility of the main commercially available gene expression panels (Oncotype DX, MammaPrint, EndoPredict, Prosigna/PAM50 and Breast Cancer Index) in the neoadjuvant setting, in order to better inform decision making for luminal BC beyond the exclusive contribution of clinico-pathological features.