Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer

Area of Science:

• Oncology
• Translational Research
• Biomarker Development

Background:

• Chemotherapy benefit varies in node-positive, estrogen receptor-positive (ER+) breast cancer.
• The Sensitivity to Endocrine Therapy (SET2,3) test measures endocrine transcriptional activity.
• Identifying patients who benefit from specific chemotherapy regimens is crucial.

Purpose of the Study:

• To report 12-year outcomes of the C9741 trial.
• To evaluate the SET2,3 test's ability to predict benefit from dose-dense chemotherapy.
• To identify patient subgroups most likely to benefit from dose-dense chemotherapy.

Main Methods:

• 1,973 patients were randomized to dose-dense or conventional chemotherapy.
• Cox models estimated hazard ratios for disease-free survival (DFS) and overall survival (OS).
• SET2,3 was tested on RNA samples from 682 ER+ cancers.

Main Results:

• Dose-dense chemotherapy improved DFS by 23% and OS by 20% overall.
• Benefits were observed in both ER+ and ER-negative subsets.
• Low SET2,3 status predicted improved outcomes with dose-dense chemotherapy, indicating benefit from low endocrine activity.

Conclusions:

• Adjuvant dose-dense chemotherapy provides sustained long-term benefits for node-positive breast cancer.
• The SET2,3 test identified ER+ breast cancer patients who benefit from dose-dense chemotherapy.
• Benefit was predicted by low endocrine activity, not tumor burden, subtype, or menopausal status.