On December 10, 2020 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that new 5-year data from the NBRST trial that will be presented in a poster spotlight discussion Thursday, December 10, 2020 from 3:30pm-4:45pm CST at the 2020 San Antonio Breast Cancer Symposium (SABCS 2020) (Press release, Agendia, DEC 10, 2020, View Source [SID1234572627]).
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The poster, entitled 5-year outcomes in the NBRST trial: Preoperative MammaPrint and BluePrint breast cancer subtype is associated with neoadjuvant treatment response and survival, contains the largest data set evaluating a genomic test in the neoadjuvant setting with long-term outcomes. These outcomes demonstrate the predictive and prognostic abilities of MammaPrint and BluePrint, and underpin both assays’ pre-operative utility.
In the 5-year results of the Neoadjuvant Breast Symphony Trial (NBRST), 22% of the tumors evaluated were reclassified from their original clinical subtype into a different molecular subtype by MammaPrint and BluePrint. This reclassification has significant implications for treatment planning, reinforcing the importance of the multi-disciplinary care team having this meaningful information at the earliest point after diagnosis to inform the decision for the timing of surgery and systemic therapy.
Importantly, the reclassification by BluePrint allowed researchers to detect more genomic diversity within pathologically ER+ and HER2 negative breast cancers than previously thought. 18% of those tumors were reclassified as Basal-Type by BluePrint (ER+/Basal) while 44% of pathologically HER2+ tumors were reclassified as Luminal- or Basal-Type by BluePrint. Of note, the response to treatment and longer term outcomes in those reclassified patients were distinctly different and aligned with the subtype identified by BluePrint.
"Genomic classification is uncovering the diversity in these pathologically-defined subsets," said Pat Whitworth, M.D., first author of the spotlight poster and a breast surgical oncologist at the Nashville Breast Center. "If a conventional HER2+ or an ER+/HER2 negative tumor is reclassified as BluePrint Basal-Type, switching to a different treatment approach, such as a HER2-targeted regimen with optimal basal coverage or different timing for surgery, may improve outcomes for those patients. With this extra layer of information, the patient and her care team are able to make important decisions at the very beginning of their journey that will be felt years down the line. Just as important, these patients should be the focus of upcoming trials."
In looking into the genomic makeup of the tumors, BluePrint could further stratify ER+ and HER2+ breast cancers as Luminal- or Basal-Type, which respond differently to treatment and could one day impact how these patients are treated. This observation echoes what was seen in a subanalysis of the APHINITY trial, also part of a spotlight poster discussion at SABCS 2020.
"The finding that a subset of ER+ HER2 negative primary breast cancers has a basal genotype on BluePrint analysis is a novel and very provocative result that compels us to study this further," said Joyce O’Shaughnessy, M.D., Director of the Breast Cancer Research Program for Texas Oncology and the US Oncology Network. "Should the ER+/basal breast cancers be treated as triple negative breast cancers, with platinum-based regimens, capecitabine post-op for residual disease and potentially with preop checkpoint inhibitors? We plan to study preop administration of platinum-based chemotherapy in patients with ER+/basal cancer to determine whether their outcomes parallel those of triple negative basal breast cancers."
Also presented at SABCS 2020 is a supporting poster on the NBRST study, "Molecular subtyping by BluePrint improves prediction of treatment responses and survival outcomes in patients with discordant clinical and genomic classification," which focused on the discordant groups within the 22% of BluePrint reclassifications displayed in the NBRST study. The data showed that molecular subtyping using MammaPrint and BluePrint is additive to pathologic assessment and thus facilitates more informed treatment decisions.
In addition, the supplemental NBRST poster reinforces the importance of genomic testing to further stratify Luminal patients. The data showed that Luminal A-Type patients have excellent outcomes on neoadjuvant endocrine therapy alone, an important consideration during the COVID-19 pandemic, while Luminal B-Type patients need additional systemic treatment.
According to James Pellicane, M.D., Director of Breast Oncology at the Bon Secours Cancer Institute, "These data confirm that BluePrint can be utilized as a tool to determine whether neoadjuvant systemic therapy or surgery followed by adjuvant therapy is the best option for a patient based on the molecular subtype of their breast cancer and its predicted response to therapy. What we’ve seen from NBRST is that certain patients, specifically the Luminal A subtypes, will respond to neoadjuvant endocrine therapy and have good long-term outcomes postoperatively with endocrine therapy alone. Others may respond to neoadjuvant endocrine therapy but because of their more aggressive biology, specifically the Luminal B subtypes, will benefit from cytotoxic chemotherapy in the adjuvant or sometimes in the neoadjuvant setting. As a surgeon, it’s comforting to know that you can triage these patients more effectively, having a better understanding of the biology of their breast cancer and how it will respond to different treatment algorithms and how that response corresponds with their long-term outcome."
These data are part of a large suite of 13 posters, spotlight sessions and an oral presentation on MammaPrint and BluePrint that were accepted to SABCS 2020, and underscore Agendia’s mission to help guide the diagnosis and personalized treatment of breast cancer for all patients throughout their treatment journey.