Efficacy of adjuvant chemotherapy schedules for breast cancer according to body mass index: results from the phase III GIM2 trial

Abstract

Background: The phase III GIM2 trial showed improved disease-free survival (DFS) and overall survival (OS) with adjuvant dose-dense (DD) as compared with standard-interval (SI) chemotherapy in women with node-positive early-stage breast cancer (BC). This exploratory analysis aimed to investigate the benefit of different schedules according to body mass index (BMI) in this trial.

Patients and methods: This analysis explored the efficacy, in terms of DFS and OS, of different chemotherapy schedules according to BMI. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used.

Results: Out of 2091 patients enrolled, 1925 with known baseline BMI were randomized in the DD versus SI comparison and therefore included in this analysis: 31.6% were overweight and 19.3% obese. Overweight and obesity were significantly associated with postmenopausal status, pT >2, and pN >2 tumors. After a median follow-up of 15.0 years (interquartile range 8.4-16.3 years), multivariable Cox survival models demonstrated no association of different BMI categories on DFS [adjusted hazard ratio (adjHR) 0.96, 95% confidence interval (CI) 0.80-1.15 and adjHR 1.11, 95% CI 0.91-1.35 for overweight and obese patients, respectively, compared to patients with normal BMI] or OS (adjHR 0.90, 95% CI 0.71-1.14 and adjHR 1.18, 95% CI 0.92-1.52 for overweight and obese patients, respectively). No significant interaction was found between BMI and treatment schedule in terms of DFS (P_{for interaction} = 0.56) or OS (P_{for interaction} = 0.19). The survival benefit of DD chemotherapy was observed irrespective of different BMI categories, with a more pronounced benefit for overweight and obese patients.

Conclusion: In node-positive BC patients, DD schedule should be considered the preferred schedule irrespective of BMI.

Keywords: body mass index; breast cancer; chemotherapy; dose-dense.

Figure 1

DFS (A) and OS (B) according to BMI category (unadjusted and adjusted analysis). Adjustment made for treatment, age, histology, pT, pN, grade, receptors, and HER2. BMI, body mass index; CI, confidence interval; DFS, disease-free survival; HER2, human epidermal growth factor receptor 2; OS, overall survival.

Figure 2

DFS benefit of chemotherapy schedule in normal weight (A), overweight (B) and obese (C) patients. BMI, body mass index; CI, confidence interval; DD, dose-dense; DFS, disease-free survival; HR, hazard ratio; SI, standard-interval.

Figure 3

OS benefit of chemotherapy schedule in normal weight (A), overweight (B) and obese (C) patients. BMI, body mass index; CI, confidence interval; DD, dose-dense; HR, hazard ratio; OS, overall survival; SI, standard-interval.

Figure 4

DFS (A) and OS (B) according to BMI category in patients with luminal tumors (unadjusted and adjusted analysis). Adjustment made for treatment, age, histology, pT, pN, and grade. BMI, body mass; CI, confidence interval; DFS, disease-free survival; HR, hazard ratio; OS, overall survival.