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William J. Gradishar, MD, FACP, FASCO


Novel Genomic Test May Predict Response to Dose-Dense Chemotherapy in Breast Cancer

By: Julia Fiederlein
Posted: Friday, July 1, 2022

Otto Metzger, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues conducted the CALGB 9471 (Alliance) trial to investigate the clinical utility of SET2,3 in estrogen receptor–positive breast cancer. The findings, which were presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 505), suggested this novel biomarker of endocrine sensitivity has the potential to identify patients who may derive a greater benefit from dose-dense chemotherapy than from conventional schedules.

“SET2,3 measures nonproliferative hormone receptor–related transcription adjusted for a baseline prognosis index derived from tumor size, nodes involved, and a four-gene molecular subtype,” the investigators remarked. “The SET2,3 index was strongly prognostic, independent of [PAM50 risk of recurrence scores tracking tumor proliferation and size (PAM50 ROR-PT)], and predicted survival benefit from dose-dense chemotherapy in premenopausal and postmenopausal women with estrogen receptor–positive cancer.”

SET2,3 testing was performed on 682 tumor samples from women with estrogen receptor–positive breast cancer who were treated with a dose-dense or conventional chemotherapy regimen in the CALGB trial. Patients with high SET2,3 scores seemed to experience significantly higher rates of disease-free survival (5 years: 85.6% vs. 69.0%; 10 years: 77.7% vs. 58.2%) and overall survival (5 years: 95.3% vs. 84.6%; 10 years: 86.9% vs. 65.9%) than those with low scores.

According to the investigators, in multivariate models, SET2,3 remained an independent prognostic variable for disease-free (high vs. low SET2,3 scores: hazard ratio [HR] = 0.46, P < .0001; high vs. low PAM50 ROR-PT scores: HR = 1.22, P = .18) and overall (SET2,3: HR = 0.36, P < .0001; PAM50 ROR-PT: HR = 1.26, P = .16) survival. Patients with low SET2,3 scores appeared to reap survival benefits from dose-dense chemotherapy (disease-free survival: P = .0998; relapse-free survival: P = .042; overall survival: P = .027); this seemed to hold true regardless of menopausal status.

Disclosure: For full disclosures of the study authors, visit

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