Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial.

PURPOSE: To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. METHODS AND MATERIALS: The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. RESULTS: We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P = .005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P = .02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. CONCLUSION: Our analysis of the BIG 02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks.

Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer.

AIM: Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials. PATIENTS AND METHODS: 2887 patients were randomly assigned in a 2×2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. RESULTS: After a median follow-up of 10.1years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR)=0.91, 95% confidence interval (CI)=0.81-1.04; P=0.16 and HR=0.88, 95% CI=0.76-1.03; P=0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR=0.86, 95% CI=0.72-1.03; P=0.10). In oestrogen receptor (ER)-positive tumours with Ki67⩾14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P=0.03, test for interaction=0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR=0.79, 95% CI=0.63-1.01; P=0.05 and HR=0.76, 95% CI=0.57-1.01; P=0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P=0.01). CONCLUSION: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.

The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial.

BACKGROUND: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. PATIENTS AND METHODS: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI >or= 30 kg/m2. RESULTS: In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34; P = 0.013). Estimated 5-years DFS was 75.9% for nonobese and 70.0% for obese patients (HR 1.20; P = 0.041). Ina multivariate model, obesity remained an independent prognostic factor for OS and DFS. CONCLUSIONS: In this study,obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed.