For patients diagnosed with ER+ breast cancer and low endocrine sensitivity (a Low SET2,3 index), dose-dense chemotherapy was associated with superior disease-free survival (DFS) and overall survival (OS) outcomes when compared to non-dose-dense regimens.
Houston, TX, June 13 2022 – Delphi Diagnostics Inc. announced today the inclusion of Delphi’s proprietary Sensitivity to Endocrine Therapy test, SET2,3, in an oral presentation entitled “Measurement of endocrine activity (SET2,3TM) related to prognosis and prediction of benefit from dose-dense (DD) chemotherapy in estrogen receptor-positive (ER+) cancer: CALGB 9741 (Alliance)” presented by Dr. Otto Metzger at the American Society for Clinical Oncology (ASCO) Annual Meeting which was held June 3-7 in Chicago, IL.
The data analyzed was from the CALGB 9741 trial, which tested both sequential versus concurrent chemotherapy administration and a conventional dosing interval versus a dose-dense interval. Patients with ER+ breast cancer then received 5 years of adjuvant endocrine therapy. In the CALGB trial, Dose-Dense chemotherapy was associated with improved disease-free survival and overall survival1. However, benefit from dose-dense chemotherapy was only reported in the ER-negative subset of patients2, and this question has since remained unresolved for patients with ER-positive cancer. Previously, the PAM50 intrinsic subtype, and ROR-PT which combines the PAM50 score with tumor size and an additional 9-gene proliferation score, were tested in CALGB 9741 but did not predict benefit from dose-dense chemotherapy in the overall population.3 The investigators obtained permission from the National Cancer Institute to test their SET2,3 assay in the ER-positive population using residual RNA from the prior study of PAM50. Samples from over 600 ER-positive cancers from the CALGB 9741 trial were tested at MD Anderson Cancer Center and sent to a clinical trial statistician for an independent analysis. The investigators were looking to determine if SET2,3 high (i.e., ≥ 2.1) is associated with favorable disease-free survival, to compare the prognostic performance of SET2,3 to PAM50 and ROR-PT, and to determine whether the efficacy of dose-dense chemotherapy depends on SET2,3.
The SET2,3index is a measure of the level of transcriptional activity that is related to estrogen and progesterone receptors (SETER/PR index), which is adjusted for the pre-treatment prognostic characteristics of tumor size, lymph node involvement, and a simple 4-gene molecular subtype. The SET 2,3 Index measures endocrine activity in the tumor, with predicted good prognosis on endocrine therapies when SET2,3 is high.
The authors found that the SET2,3 index was strongly prognostic, independent of ROR-PT (Prosigna), and predicted survival benefits from dense-`dose chemotherapy in pre-and postmenopausal women with ER+ cancer. The predicted benefit from dose-dense chemotherapy was independent of menopausal status and of genomic HER2 status (gene expression level or intrinsic subtype). Evaluating the components of the SET2,3 index, the authors found that the SETER/PR index of endocrine transcriptional activity in the tumor provided most of the predictive information for the benefit from dose-dense chemotherapy in ER+ breast cancer.
The findings suggest the following clinical considerations:
- Patients diagnosed with lymph node-positive ER+ breast cancer and low endocrine sensitivity (a Low SET2,3 index), experienced improved disease-free survival (DFS) and overall survival (OS) outcomes following dose-dense chemotherapy compared to non-dose dense regimens. This result was not affected by menopausal status.
- The state of endocrine activity in breast cancer predicted benefit from dose-dense chemotherapy, whereas measures of tumor burden and proliferation did not.
- Based on this novel finding, the SET2,3 biomarker, particularly its SETER/PR component, should be evaluated in other trials that include contemporary taxane-based chemotherapy regimens and/or dose-intense treatments.
“Our findings can be summarized as follows: SET2,3 identifies patients diagnosed with ER+ breast cancer with significantly lower chances of experiencing disease recurrence; SET2,3 outperformed PAM50 in its ability to predict patient’s outcome and in its ability to identify a subset of patients experiencing greater benefits with dose dense chemotherapy,” said study presenter Otto Metzger, MD, of Dana-Farber Cancer Institute and Alliance for Clinical Trials in Oncology.
Dr. Metzger continued, “Our findings may define a new paradigm by demonstrating that measurement of endocrine transcriptional activity through SET2,3 to be an important factor for predicting benefits of chemotherapy in addition to classic metrics of tumor cell proliferative activity through pathology and proliferation-driven genomic tools. If confirmed by future studies, the biomarker could be the basis for the first test for identifying which of these patients diagnosed with ER+ breast cancer stands to have the best responses to dose-dense chemotherapy.”
“This blinded analysis of the SET2,3 test yielded results that are both clinically and scientifically interesting, demonstrated clinical validity, and illustrated again that the test independently added complementary information to another molecular prognostic test,” said Fraser Symmans, MD, of MD Anderson Cancer Center, and co-inventor of the SET2,3 assay. He added, “We are very grateful to the Breast Cancer Research Foundation and the National Cancer Institute for their support of this project, and to our colleagues in the Alliance for Clinical Trials in Oncology.”
Additional information and details for the presentation at ASCO can be found below:
Title: Measurement of endocrine activity (SET2,3) related to prognosis and prediction of benefit from dose-dense (DD) chemotherapy in estrogen receptor-positive (ER+) cancer: CALGB 9741 (Alliance).
- Abstract Number: 505
- Authors: Otto Metzger, Karla V. Ballman, Jordan Campbell, Minetta C. Liu, Jennifer A. Ligibel, Eveline Chen, Lili Du, W. Fraser Symmans
- Presentation date & time: Oral Abstract Session:Breast Cancer – Local/Regional/Adjuvant; June 7, 2022, 10:45am ET
- Citron M et al. JCO 2003;
- Berry D, et al JAMA 2006
- Liu M et al. npj Breast Cancer 2016.
About Delphi Diagnostics
Delphi Diagnostics Inc. is a Texas-based company with an exclusive worldwide license to commercialize past, present, and future breast cancer diagnostics and intellectual property developed by Dr. Fraser Symmans at MD Anderson Cancer Center. The Sensitivity to Endocrine Therapy test (SET) measures Sensitivity to Endocrine Therapy in all stages of HR+HER- breast cancer. The patent for SET has been granted in the European Union and is verbally allowed in the United States and is pending in five further jurisdictions. The SET test is currently being used in prospective clinical trials. Delphi’s mission is to make the SET test available to breast cancer patients, maximize disease-free survival while minimizing toxicity, and avoid non-beneficial treatments. Delphi recently completed its third capital raise. Investors include several family offices and professional investors, as well as a venture capital fund, DigitalDX Ventures in Silicon Valley. To learn more, visit www.delphi-diagnostics.com
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