The efficacy of aromatase inhibitors in treating hormone-dependent breast cancer patients has been demonstrated in several clinical trials, where a significant increase in disease-free survival has been shown using third-generation aromatase inhibitors [4–8, 13]. However, as with tamoxifen, resistance to these therapies does develop and patients recur. We recently showed that tamoxifen-treated patients whose tumors were of high genomic grade were associated with a worse outcome than those with a low GGI. However, since the actions of tamoxifen (ER antagonist) and aromatase inhibitors (prevention of estrogen synthesis) are inherently different, we sought in this study to assess whether high GGI levels would also be associated with worse outcome in patients treated with aromatase inhibitors.
Altogether, these results confirm our previous findings, i.e. that the GGI is a good predictor of relapse in ER-positive breast cancer patients . Indeed, this analysis supports the GGI as a good predictor of relapse in the sample of 48 postmenopausal patients with hormone-positive breast cancer of the prospective BIG 1–98 trial with available frozen tissue and suggests that higher values of the GGI are associated with an increase in the hazard of a relapse, with each 10-unit increase in GGI resulting in an approximate 11% increase in the hazard rate. Also considering the GGI as a binary variable defined by the median value, provided evidence for a relationship between high GGI values and increase risk of relapse. Using time-dependent, incident/dynamic, ROC/AUC methodology, estimated AUC values between 73% and 78%, occurring during the first 36 months of enrollment, suggest that the GGI has good predictive ability for relapse, with the best predictive ability occurring at approximately 27 months. However, false-positive rates using the GGI were high, remaining above 40%.
Exploratory subgroup analyses within nodal status or treatment suggest that high values of GGI indicate worse outcomes. When the performance of GGI was compared within nodal status, the hazard of relapse was significantly greater for patients with GGI at or above the median within the subgroup of patients with node-positive disease.
Analyses of GGI performance within treatment assignment were somewhat limited, due to the small number of cases with available samples for patients treated with tamoxifen. Within the subgroup of patients randomized to treatment with letrozole, the hazard of relapse was significantly greater for patients with GGI at or above the median when compared to patients with GGI values below.