On December 12, 2024 Agendia, Inc., reported it will be presenting new data highlighting MammaPrint and BluePrint utility in guiding treatment decisions for patients with early-stage breast cancer (Press release, Agendia, DEC 12, 2024, View Source [SID1234649093]). The findings will be presented in two spotlight presentations and two posters at the San Antonio Breast Cancer Symposium 2024 (SABCS), on Wednesday, December 11th and Thursday, December 12th.

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One poster spotlight, titled "Association of MammaPrint with gene expression pathways predictive of resistance to cyclin-dependent kinase inhibition," presented by Adam Brufsky, MD, PhD, Professor and Associate Chief of Hematology and Oncology at UPMC Hillman Cancer Center, examined 5,657 patients with early-stage HR+HER2- tumors enrolled in the ongoing prospective, observational FLEX Trial (NCT03053193). The analysis evaluated the correlation between MammaPrint and gene expression patterns associated with Retinoblastoma (Rb) loss-of-function and CDK4 independent cellular proliferation to identify which MammaPrint Risk categories may be resistant to CDK4/6 inhibition.

A linear correlation was observed between increasing MammaPrint Risk and increasing Rb loss-of-function gene expression, suggesting that MammaPrint High 2 tumors have the highest probability of CDK4/6 resistance. Additionally, MammaPrint High 2 tumors were most likely to exhibit high cell proliferation independent of CDK4 activity (43.0%), in comparison to Ultra Low (0.1%), Low (0.5%), and High 1 (1.8%) tumors (p < 0.001). These data provide the first evidence for the utility of a commercially available signature to potentially predict resistance to CDK4/6 inhibition and help patients receive more targeted and individualized therapies.

The second poster spotlight, titled "MammaPrint and BluePrint Predict Pathological Response to Neoadjuvant Chemotherapy in Patients with HR+HER2- Early-Stage Breast Cancer Enrolled in FLEX," presented by Joyce O’Shaughnessy, MD, National Principal Investigator of the FLEX Study, Director, Breast Cancer Research, Baylor University Medical Center, Texas Oncology and the Sarah Cannon Research Institute in Dallas, TX, evaluated MammaPrint and BluePrint in predicting pathological response to neoadjuvant chemotherapy among 457 HR+HER2- breast cancer patients enrolled in FLEX.

Rates of Pathological Response (PR), including pathological Complete Response (pCR) and minimal residual cancer burden (RCB-I), were highest in High 2 Basal (43.4%) and Luminal B (21.4%) tumors, with High 2 tumors overall showing better PR rates (32.7%) compared to High 1 tumors (9.5%). Multivariate analysis indicated that only MammaPrint High 2 was significantly associated with likelihood of PR, after adjusting for clinical confounders. Overall, MammaPrint and BluePrint proved effective in predicting neoadjuvant chemosensitivity in HR+HER2- breast cancer, which may enable downstaging and improve overall outcomes.

"The findings from these two studies highlight the ability of genomic testing using MammaPrint and BluePrint to predict patient response to therapies like chemotherapy, and may be able to predict benefit from CDK4/6 inhibitors," said Dr. O’Shaughnessy. "The ongoing data that continues to be generated through FLEX is building evidence that these tests may help unlock optimal treatment plans based on the patient’s tumor biology."

Abstracts Accepted as Posters

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine – Biology is Still King (Rahman, R., et al.)
A pooled analysis was conducted on 404 clinical T3 breast cancer patients from the NBRST, FLEX, and MINT trials undergoing neoadjuvant chemotherapy. MammaPrint (MP) and BluePrint (BP) subtyping showed higher pathological complete response (pCR) rates across all MP High Risk subtype tumors (Basal (32.5%, HER2 53.7%, Luminal B 8.6%) compared to MP Low Risk Luminal A subtype tumors (0% pCR). Menopausal status, nodal status, and grade were not significant predictors of pCR response. High Risk tumors had significantly higher pCR rates, suggesting MammaPrint Low Risk, cT3 tumors are unlikely to achieve pCR to neoadjuvant chemotherapy, suggesting these patients may avoid neoadjuvant chemotherapy despite their large tumor size.

FLEX: A Real-World Evidence, Full Transcriptome Study in 30,000 Patients with Early-Stage Breast Cancer (Maganini, R., et al.)
The FLEX Study, a large, multi-center, real-world evidence, whole transcriptome, observational breast cancer study (NCT03053193), has grown substantially since its launch in April 2017. With more than 17,000 patients enrolled across 100 sites in the US and around the world, FLEX includes over 40 sub-studies in several topics. Participants are of all racial and ethnic backgrounds with stage I, II, or III early-stage breast cancer, aiming for a representative data set. The study has produced more than 10 clinical evidence pieces on diversity and includes 1,377 self-identified Black, 530 Latin American/Hispanic, and 353 Asian and Pacific Islanders, making FLEX the most diverse study on EBC patients to date.

"These data significantly enhance our understanding of MammaPrint and BluePrint’s growing clinical applications," said William Audeh, MD, MS, Chief Medical Officer at Agendia. "Our findings reinforce the importance of precision medicine, as it allows us to tailor treatment strategies, including neoadjuvant chemotherapy consideration, incorporating immunotherapies, and potentially sparing patients from the harms of unnecessary chemotherapy. As we continue to gather data from studies like FLEX, we are solidifying the role of these genomic assays in guiding personalized treatment decisions for breast cancer patients."

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