TEST:

MammaPrint

We used this methodology to compare GCNN+LRP to GCNN+SHAP and to more classical ML-based feature selection approaches. Utilizing a large breast cancer gene expression dataset we show that, while feature selection with SHAP is useful in applications where selected features have to be impactful for classification performance, among all studied methods GCNN+LRP delivers the most stable (reproducible) and interpretable gene lists.

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 study demonstrates an increasing trend in use of pretherapy genomic profiling over time, which is consistent with observed clinical trends. Over 50% of patients underwent upfront surgery when pretherapy genomic profiling was used to guide decision-making, who would have otherwise been offered neoadjuvant chemotherapy. We observed de-escalation of breast specific surgery in more patients with pretherapy genomic profiles.

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.

The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment.

Participants must not have received any prior treatment for their current breast cancer, including chemotherapy, immunotherapy, biologic, or hormonal therapy, and must be candidates for doxorubicin, paclitaxel, and durvalumab therapy. Summary Statement This study activated on 10/30/2023. As of December 31, 2023, there had been five patients registered to MammaPrint screening step, all of whom did not to go on to randomization due to ineligible MammaPrint status.

P2; Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Sep 2029 | Trial primary completion date: Jan 2024 --> Sep 2024

P=N/A; N=300; Not yet recruiting; Sponsor:Precise Dx, Inc.

Supported by Agendia. Overview: During this symposium, Jaime Alberty MD, FACS (Breast Surgeon) and William Audeh MD, MS (Medical Oncologist & Chief Medical Officer at Agendia) will discuss the latest data and share case studies leveraging MammaPrint® + BluePrint® gene expression profiling to optimize treatment plans for patients with Early-Stage ER+ Breast Cancer.

P=Obs | N=25,000 | FLEX (NCT03053193) | Sponsor: Agendia | "Agendia, Inc., announced today it will share new data from the ongoing prospective, observational FLEX Trial (NCT03053193) in two poster presentations at the 41st Annual Miami Breast Cancer Conference (MBCC), taking place March 7 – 10th, 2024...The first poster....Results showed that patients with MP High 2 tumors, including Luminal B and Basal subtypes, are more likely to achieve a pCR in response to AC-T, while the addition of anthracycline to the therapy regimen does not appear to improve pCR rates for patients with MP High 1, Luminal B-type tumors."

These results suggest that a subset of high risk HR+HER2- breast cancers is highly sensitive to immunotherapy, and by using a specific and sensitive selection strategy patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (i.e., pCR rate > 65-70%). ImPrint, an FDA IDE-enabled assay currently being further evaluated in I-SPY2, may represent the way to identify patients for IO that best balances likely benefit vs risk of serious immune-related adverse events.

Implementing Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system.

P3; Trial completion date: Dec 2027 --> Mar 2028

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

The prediction accuracy exceeded 90% in several subgroups, with the highest prediction accuracy of 95.7% in the subgroup that met Ki-67 <20 and HG 1~2 and premenopausal status. Our machine learning-based predictive model has the potential to complement existing MGAs in ER+/HER2- breast cancer.

P2 | N=67 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2023 ➔ Dec 2024

Findings suggest ME3 would have more accurately predicted chemotherapeutic response over MP. While both methods identified the cases with significant responses to chemotherapy, MP overpredicted the number of cases that would benefit. Therefore, ME3 may represent a more accurate, accessible, and cost-effective way to predict response to NA chemotherapy.

The customized 19-gene assay has a high concordance with MammaPrint in predicting recurrent risk and evaluating effects of adjuvant chemotherapy, especially in the low- and medium-risk groups that can be exempted from chemotherapy. A larger cohort is warranted to further validate this assay.

No abstracts available

"Agendia®, Inc., announced...that the first patient to use MammaPrint® as an enrollment biomarker for the DEBRA Trial is to be enrolled. The Phase III NRG Oncology De-Escalation of Breast Radiation (DEBRA) Trial (NCT04852887), is a clinical study looking at safely reducing the use of breast radiation after lumpectomy for people with low-risk, early-stage breast cancer."

Sponsored by Leram Genoma

An increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease.

The CLEVER trial provides proof-of-principle that therapeutic targeting of dormant BC is feasible and active in eliminating DTCs by targeting dormancy-specific mechanisms. Follow up for recurrence and survival is ongoing.

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

This exploratory analysis of the MINDACT trial estimated an 8-year low LRR rate of 3.2% after BCS. The 70-gene signature was not independently predictive of LRR perhaps because of the low number of events observed and currently cannot be used in clinical decision making regarding LRR. The overall low number of events does provide an opportunity to design trials toward de-escalation of local therapy.

P2; Trial completion date: Mar 2028 --> Dec 2028 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: Dec 2024 --> Dec 2028

A transforming growth factor β signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

The combined model incorporating clinicopathologic and MRI features showed potential in predicting the low MammaPrint risk group, and may support decision-making in clinical settings with limited access to MammaPrint.

The Ang/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

The high GET risk results can be predicted using traditional clinicopathological factors: tumor size, progesterone receptor, histological grade, HER2, and Ki-67. These results will be useful for treatment decision-making among clinically high-risk patients with HR-positive/HER2-negative and node-positive disease, helping to identify patients to whom the GET assay may not apply.

P2; This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial.

In this study, we identified the clinical and genetic characteristics of ER + /PR- breast cancer patients in China. Distinct PR statuses indicated different biological processes of ER + breast cancer and survival outcomes. Future treatment strategies may need to be tailored for ER + /PR- patients.

P3; Initiation date: Jul 2024 --> Nov 2023

P3; Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> Jul 2024

To our knowledge, we are the first to establish easy-to-use nomograms to predict the individualized binary (high vs low) and the quartile categorized (ultra-high, high, low and ultra-low) risk classification of 70-GS test with fair performance, which might provide information for treatment choice for those who have no access to the 70-GS testing.

More robust analysis of these two populations needs to be performed to confirm the presented data. TABLE 1 - Profile of high genomic risk AGEMA-BRA

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.

Table 1. Characteristics of patients and tumor according to risk (AGEMA-BRA)

These data demonstrate MammaPrint and BluePrint utility to predict the likelihood of achieving pCR after NCT in HR+HER2- ESBC. Although both MP High Risk groups exhibit chemosensitivity, High 2 tumors have higher chemosensitivity than High 1 tumors. MP High 2 status can be utilized to identify ER+ patients who are the most likely to experience pathologic downstaging and pCR after NCT.

In a database of patients with EBC of whom 98% did not develop metastasis within 5 years, we observed in a small series of chemotherapy naïve patients with early DR and UHL-defined clinical low-risk tumors, that nearly half had a genomically high risk of distant metastasis. Albeit numerically higher than the matched-control group, this observation was not significant and would warrant a larger sample size and power to confirm these results. Genomic versus Clinical Risk by MyMammaprint.com

This is the first study to investigate the distribution of Response Predictive Subtypes in ILC, which will be beneficial to optimize the treatment selection for patients with early-stage HR+/HER2- ILC. Though the percentage of ImPrint+ is lower in ILC, this study revealed a small subset of patients in ILC with potential response to Immunotherapy. Furthermore, these results underscore the heterogeneity of ILC tumors and generate further hypotheses to investigate the immune cell abundance in ILC compared to IDC and correlate immune cell abundance to ImPrint status.