A new genomic test designed to measure the endocrine sensitivity of estrogen receptor–positive breast cancer has the potential to identify patients diagnosed with the disease who could benefit more from dose-dense chemotherapy—a regimen in which chemotherapy is administered more frequently than usual—as compared to non–dose-dense regimens. These findings will be presented by Metzger et al at the 2022 ASCO Annual Meeting (Abstract 505).
The investigators found that women with estrogen receptor–positive breast cancer that scores low for a biomarker called SET2,3 (indicating endocrine resistance) benefited far more from dose-dense chemotherapy than patients with higher scores. The results applied to premenopausal as well as postmenopausal women.
If confirmed by future studies, the biomarker could be the basis for the first test capable of identifying patients diagnosed with estrogen receptor–positive breast cancer who stand to have the best responses to dose-dense chemotherapy, said study presenter Otto Metzger, MD, of Dana-Farber Cancer Institute.
Study Background and Results
The SET2,3 (sensitivity to endocrine therapy) index measures the activity of genes involved in estrogen and progesterone receptor signaling and excludes genes related to cell proliferation. A high SET2,3 score indicates higher endocrine sensitivity and the potential to derive greater benefits from adjuvant endocrine therapy.
For the new study, researchers conducted SET2,3 testing on 682 tumor samples from women with estrogen receptor–positive breast cancer who participated in the CALGB 9471 clinical trial, which compared dose-dense chemotherapy schedules to conventional schedules.
They found that patients with highly endocrine-sensitive tumors—and high SET2,3 scores—lived longer before their disease returned (85.6% vs 69% at 5 years, and 77.7% vs 58.2% at 10 years) and lived longer overall (95.3% vs 84.6% at 5 years and 86.9% vs 65.9% at 10 years) than patients with less sensitive tumors. They further found that SET2,3 was a far better indicator of a patient’s prognosis than an often-used genomic test of tumor cell proliferation named PAM50. The investigators then explored whether SET2,3 could fill the need for a test to identify patients with estrogen receptor–positive breast cancer who are likely to derive a greater magnitude of benefit with dose-dense chemotherapy following surgery for operable breast cancer.
Dr. Metzger noted that these findings highlight the importance of evaluating endocrine sensitivity to estimate prognosis and potentially tailor therapies for patients facing a breast cancer diagnosis.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
