TEST:

BluePrint

(early data and active trial) Who may benefit from the addition of anthracycline to their chemotherapy regimen (AC-T/TC)? Who may benefit from extended endocrine therapy?

(early data and active trial) Who may benefit from the addition of anthracycline to their chemotherapy regimen (AC-T/TC)? Who may benefit from extended endocrine therapy?

We selected 108 CLL patient samples with genetic annotation and exposed them ex-vivo to small-molecule inhibitors used clinically (ibrutinib/BTKi, duvelisib/PI3Ki, trametinib/MEKi, everolimus/mTORi, selinexor/XPO1i) or targeting key signaling pathways (compound 26/TLRi, MK2206/AKTi, nutlin-3a/MDM2i, IBET872/BETi) for 48h. In conclusion, the addition of targeted pathway perturbations to the GEP of primary CLL samples can greatly enhance the potential for molecular and functional classification of disease and subgroups. Our study provides a blueprint to use perturbed omics profiling and interaction testing to link disease drivers to pathway activation and function.

Finally, consistent with DNA hypomethylation reflecting the proliferative history of MM, the PR subtype had the most pronounced DNA hypomethylation. Notably, the PR subtype had reduced DNAm at E2F1 motifs and E2F1 exclusively bound unmethylated regions of the genome, suggesting the DNAm restricts the proliferative program of high-risk MM.

No abstract available

No abstract available

Among patients with high molecular-risk HR+/HER2- EBC, the MP-High2, BP-Basal-type, and ImPrint positive signatures identified a partially overlapping subset of patients who were more likely to achieve pCR in response to neoadjuvant chemotherapy +/- targeted agents or immunotherapy compared to patients with MP-High1, BP-Luminal-type, and ImPrint negative disease. I-SPY2.2 is incorporating the use of these biomarkers to molecularly define specific patient populations and optimize treatment selection.

We performed surgery, postoperative radiotherapy, and hormonal therapy in a breast cancer patient with vascular EDS without major complications.

"Agendia, Inc. today announced that it has obtained certification from the European Union (EU) In Vitro Diagnostic Medical Device Regulation (IVDR) for three products, including its MammaPrint FFPE Microarray, BluePrint FFPE Microarray, and MammaPrint and BluePrint NGS Kit. These products are classified as Class C under this regulation."

These mutations impact cancer onset age and severity, underscoring the need for targeted testing and screening. The current study enhances cancer detection, prevention, and cure strategies.

MammaPrint and BluePrint classification highlights racial disparities in the distribution of distinct High Risk molecular subtypes among HR+HER2- early BC. However, survival at 3 years was driven by molecular subtype, independent of race, after controlling for potential confounders. These data highlight the importance of tumor genomic testing to inform treatment decisions as we strive to reduce racial survival disparities among Black females with BC.

Patients with Luminal Low-Risk breast cancer had a long-term benefit from 2 years of adjuvant tamoxifen up to 20 years beyond primary diagnosis. No significant benefit was seen for Ultralow or Luminal High-Risk patients. This highlights the importance of extended follow-up to understand treatment benefit and the importance of individualized management for ER-positive patients.

The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.

Sponsored by Agendia NV

Early-stage HR-positive breast carcinomas have low TIL levels regardless of the recurrence risk, molecular subtype, and HER2- low status. These cancers are markedly enriched by HER2-low phenotype, which might have therapeutic implications due to the recently approved anti-HER2 antibody-drug conjugate.

P2 | N=28 | Recruiting | Sponsor: University of Illinois at Chicago | Not yet recruiting ➔ Recruiting

P2 | N=28 | Not yet recruiting | Sponsor: University of Illinois at Chicago

P=Obs | N=25,000 | FLEX (NCT03053193) | Sponsor: Agendia | "Agendia, Inc. today announced it will present new data on the 3-year outcome of patients with hormone receptor-positive (HR+), HER2-negative early-stage breast cancer when treated with two different chemotherapy regimens at the 2024 Annual American Society of Clinical Oncology (ASCO) Meeting, taking place in Chicago, IL. on May 31st, 2024....Results showed that patients with MammaPrint H1 Luminal B-Type tumors demonstrated similar 3-year outcomes when treated with either TC (97.1%) or AC-T (95.3%), suggesting that patients who are classified as H1 may be able to avoid the toxicity of an anthracycline. However, patients with MammaPrint H2 Luminal B-Type tumors demonstrated a significantly higher relapse-free survival when treated with AC-T (97.7%) than with TC alone (86.4%). These findings indicate that MammaPrint H2 tumors benefit from the addition of an anthracycline to their adjuvant chemotherapy regimen."

These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.

"Agendia, Inc., announced today that new data on its comprehensive genomic tests will be presented at the American Society of Clinical Oncology Annual Meeting (ASCO), taking place May 31st – June 4th, 2024, in Chicago, Illinois....The two abstracts that have been selected by ASCO for oral discussion will 1) feature an investigation of underlying biology that mediates immune therapy response and, 2) will provide an evaluation of the MammaPrint Index and 3-year recurrence-free interval in patients treated with CT, with and without anthracycline. Both presentations utilize whole transcriptome data from the prospective, observational real-word evidence FLEX Study (NCT03053193)."

Our study showed a high rate of discordance between clinical and genomic risk, a rate of 49% between clinical high-risk and genomic high-risk patients, highlighting the importance of these assays in the decision-making of breast cancer patients. This represents the first cohort to evaluate MammaPrint+BluePrint in a Latin American population. A noteworthy result was identifying a significant proportion of our cohort as low-risk through genomic assay, sparing them from the toxic effects and expenses associated with chemotherapy.

Here, the association of MP index and 3-year (yr) Recurrence-Free Interval (RFI) was evaluated in pts with HR+HER2-, genomically High Risk Luminal B-Type EBC treated with taxane and cyclophosphamide (TC) vs anthracycline + TC (AC-T)... These data show that among pts with Luminal B-Type tumors, MP H2 have significantly worse 3-yr RFI than pts with MP H1 tumors when treated with TC. This further supports ongoing research demonstrating the significant benefits of anthracycline-based CT for treating H2 Luminal B-Type tumors. Conversely, MP H1 tumors do not appear to benefit from the addition of anthracycline to CT regimen.

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

These findings are consistent with the poor clinical outcomes previously reported for PPBC. Increased frequency of MP High 2 tumors and immune biology indicate that PPBC might benefit from adding immunotherapy, to be explored in future trials.

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.

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.

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.

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.

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.

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.

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