Compared with the standard interval adjuvant chemotherapy, dose-dense schedule is proved to increase disease-free survival (DFS) in node-positive early breast cancer (EBC) patients (pts). To date, GIM2 is the only trial supporting the role of dose-dense chemotherapy in pts with hormone receptor-negative (HR-) or hormone receptor-positive tumours (HR+) (Del Mastro et al. Lancet 2015). To further refine the evidence of treatment effect in the HR+ subgroup, a composite index of risk was developed including clinico-pathological features.
The randomized phase III GIM2 trial enrolled 2091 pts with node-positive EBC (primary endpoint: DFS). A continuous, composite measure of treatment benefit was determined from a Cox model incorporating potential predictive factors (age: 25-40/41-55/56-71; histological grade: 1 + 2/3; HR status: positive/negative; ki-67 levels: ≤20%/>20%). Subpopulation treatment effect pattern plot methodology was used to reveal differential treatment effects on DFS according to composite index. The study analyzed the cohort of pts with HER2- (N = 1127) disease with a special focus on HR+ disease (N = 980).
On average, the magnitude of benefit with dose dense chemotherapy versus standard chemotherapy widely varied according to composite measure of specific features. In the HER2- subgroup, the highest benefit was observed in pts with G3, HR-, >10 positive nodes, age 20% (hazard ratio for DFS 0.57, 95% CI 0.35-0.94). Notably, among pts with HR+ disease, the following clinic-pathological characteristics conferred the highest benefit: G3, ≥4 positive nodes, age ≥56 yrs, ki-67 > 20% (hazard ratio for DFS 0.66, 95% CI 0.38-1.15).
Composite risk evaluation and corresponding subpopulation treatment effect pattern plot methodology suggest that benefit of dose dense adjuvant chemotherapy is not confined to triple negative EBC.
Clinical trial identification
Legal entity responsible for the study
Gruppo Italiano Mammella
All authors have declared no conflicts of interest.