TEST:

BluePrint

High rates of discordances between BP and clinical factors/IHC were identified in this Black patient population. Reclassification sometimes affected treatment decisions, leading to favorable results such as pCR after NAC. Our findings suggest that genomic profiling at time of CNB could be beneficial for Black patients, as treatment decisions based on reclassifications could potentially improve outcomes.

"Agendia®, Inc...announced...that the company’s 80-gene molecular subtyping assay, BluePrint®, is now included in the latest version of German Gynecological Oncology Group (AGO) guidelines. The assay was added to the list of predictive factors for neoadjuvant chemotherapy decision making."

P=N/A, N=50, Recruiting, Stryker Trauma GmbH | Not yet recruiting --> Recruiting

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."

Chemotherapy-free neoadjuvant regimen with DTP in HER2-enriched EBC showed high pathologic response rates comparable to that with chemotherapy. This DTP regimen may provide an effective, relatively non-toxic, and biologically driven alternative to standard of care chemotherapy in this HER2-enriched subset of EBC.

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

Sponsored by BluePrint Medicines

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.

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.

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.

Our study showed that HER2-low and HER2-0 tumors are clinically and biologically similar. The differences in ERBB2 and low-level genome wide expression detected between HER2-low and HER2-0 should be further investigated to determine how these changes affect tumor biology and treatment benefit. The biological heterogeneity among IHC-defined HER2-negative tumors was better captured by MammaPrint and BluePrint than IHC.

These studies provide a broader understanding of how differential gene expression patterns, identified with MammaPrint and BluePrint, are unique to racial/ethnic groups and can impact treatment outcomes. Overall, the FLEX study strives to use MammaPrint, BluePrint, and newly developed immune signature, ImPrint, along with full transcriptome data to improve precision medicine in early-stage breast cancer.

PILHLE-001, as a single-arm, single-center phase â…¡ trial, enrolled patients with previously untreated HR-positive (ER or PR > 1%) and HER2-low (IHC 2+/FISH negative) invasive EBC (TNM stage II-III) to receive pyrotinib 320mg QD and four Q3W of epirubicin-cyclophosphamide followed by four Q3W of docetaxel. The PILHLE-001 trial first revealed that neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and acceptable toxicity in patients with HR-positive/HER2-low (IHC 2+/FISH negative) EBC, and this regimen warrants further investigation in phase III randomized controlled trials.

This is a randomized phase II study that will evaluate the anti-tumor effect of capecitabine compared to physician's choice endocrine therapy as second line therapy for adult ( >18 years) patients with non-Luminal A HR+/HER2- metastatic or unresectable locoregional invasive carcinoma (NCT 05693766)...Enrollment opened on June 1, 2023. We anticipate opening the trial at the external sites before the end of 2023.

Previous trials have demonstrated the utility of MammaPrint UltraLow Risk in patients with clinically low risk features. In this large real-world evidence study of patients with early-stage breast cancer, UltraLow Risk tumors can be identified across all clinical categories. Overall, we report a substantial number of premenopausal patients with UltraLow Risk tumors, and these young women would be good candidates for treatment optimization.

Survival outcomes at 3 years were comparable between Black and White patients. MP and BluePrint more precisely stratified tumors resulting in distinct 3- and 10-year outcomes, independent of race, beyond clinical subtype alone. Additionally, the subset of Black patients with Low Risk, Luminal A-Type tumors had excellent 10-year survival outcomes.

There were additional clinical and genomic differences between tumors from Latin and White patients, even when controlling for age, T stage, N stage and clinical subtype. Particularly, there were more type 2 diabetes, BMI obese, BluePrint Basal, and ImPrint Immune Sensitive among Latin patients. In addition, transcriptomic differences between obese Latin and matched White patients were found in Luminal B subgroup that may contribute to the aggressive tumor biology; immunoglobulin genes and immune related pathways were associated with higher expression in Latin patients.

P2 | N=25 | Recruiting | Sponsor: University of Illinois at Chicago

No abstract available

"Agendia, Inc...announced...the publication of the Multi-Institutional Neoadjuvant Therapy MammaPrint Project I (MINT) trial, a prospective study designed to evaluate the utility of molecular profiling alongside traditional pathologic and clinical prognostic factors in predicting the response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC)."

While MM is characterized by a profound loss of DNAm, the DNAm retained in actively transcribed gene bodies suggests a role in expression. MM subtypes have distinct epigenetic programs with the high-risk MS and PR subtypes having divergent epigenetic programs. Higher levels of DNAm in the MS subtype are specific to NSD2 overexpression and may result from excessive H3K36me2 being recognized by the PWWP domains of DNA methyltransferases.

P4; Patients with genomically High Risk tumors, defined by MammaPrint with or without BluePrint, respond better to NCT and have a higher likelihood of nodal downstaging compared with patients with gLuminal A tumors. These genomic signatures can be used to select node-positive patients who are more likely to have nodal downstaging and avoid invasive surgical procedures.

P2; Trial completion date: May 2037 --> Aug 2037 | Initiation date: Jun 2023 --> Sep 2023 | Trial primary completion date: May 2027 --> Aug 2027

Group A breast cancer, which has always been unquestionably diagnosed as HER2 amplification, was more likely to be HER2 negative and derived less benefit from anti-HER2 neoadjuvant chemotherapy. Group A breast cancer should be distinguished from classical HER2-positive breast cancers when assessing HER2 FISH, and a larger cohort of Group A patients should be included in further studies.

In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

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

"At the 2023 ASCO Annual Meeting, Agendia, Inc...will present data that proves MammaPrint can predict chemotherapy sensitivity in women with early-stage, HR+HER- breast cancer. The research examined the clinical utility of MammaPrint’s two High Risk subcategories, High 1 (H1) and High 2 (H2), as an indicator of a woman’s predicted response to chemotherapy and five-year outcomes, in combination with BluePrint’s® molecular subtyping, to guide treatment decisions."

"At the 2023 ASCO Annual Meeting, Agendia, Inc...reinforces its commitment to progressing research of racial disparities in breast cancer through two poster presentations. Building off the research presented at the 2022 annual meeting, which found that BluePrint identifies stark racial disparities among women with HR+HER2- tumors...Agendia will also present a poster on MammaPrint’s ability to predict chemotherapy response in women with high-risk early-stage breast cancer, and an oral presentation on the ability of genomic biomarkers to predict a woman’s response to immunotherapy."

No abstracts available

No abstracts available

the analysis of data and outcomes in the elderly population of the AGEMA-BRA study with high clinical risk, demonstrated limited accuracy and low agreement in the stratification into high and low risk between the profile by IHC and the MP/BP. The use of the genomic platform may have been relevant in risk stratification and outcomes in this population. Studies with a larger sample and longer FU are needed to confirm the usefulness of genetic signatures in the de-escalation of systemic treatment in the elderly population with high clinical risk.

There was discordance between clinical and molecular risk in 38% of our cohort, 20% were cLR/MP and 18% were cHR/MP LR. The decision to give NAC was primarily driven by clinical risk as only 1 patient with cLR/MP HR received NAC. Amongst cHR/MP LR 87% did not get NAC, but this appears to have been a clinical decision as only 7 of these patients had a pre-operative oncology visit at which MP/BP was mentioned.

Unlike HR+HER2- tumors, these data suggest that race may not influence the biology underlying cHER2 tumors. However, there was genomic heterogeneity among cHER2 tumors identified by BluePrint, independent of race. Overall, the rate of BluePrint classification among cHER2 tumors was comparable to NBRST and APHINITY, which demonstrated distinct treatment response and outcome based on BluePrint genomic subtype.

Overall, the FLEX study strives to use full transcriptome data to improve precision medicine in early-stage breast cancer. Clinical trial information: NCT03053193.

Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients...The 1st patient was included in October 2022, initiating the 2-year inclusion period and 10 years FU per patient. Clinical trial information: NCT05297617.

P2; Trial completion date: Aug 2023 --> Feb 2025 | Trial primary completion date: Mar 2023 --> Sep 2024

P2 | N=64 | Recruiting | Sponsor: Sonya Reid | Not yet recruiting ➔ Recruiting

P=N/A; N=1470; Recruiting; Sponsor:West German Study Group

MP/BP also further supported decision to administered NCT in the majority (85%) of patients with MP High Risk. Our findings support the utility of MP/BP in high clinical risk HR+/HER2- EBC to guide neoadjuvant therapy decision and provide further information and confidence to clinicians and patients for shared-decision making.

Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients...The primary endpoint is distant metastasis free survival defined as the time from date of registration to date of 1st event of distant recurrence, death, or 2d primary non-breast invasive cancer. The 1st patient was included in Oct 2022, initiating the 2-year inclusion period.

P2 | N=67 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jan 2022 ➔ Jun 2023