Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013

Abstract

Purpose The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in Translational Breast Cancer Research Consortium (TBCRC) 013. Patients and Methods TBCRC 013 was a multi-center prospective registry evaluating the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From 07/2009–04/2012, 127 patients from 14 sites were enrolled; 109 patients (86%) had pre-treatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with 21-gene RS using log-rank, Kaplan-Meier, and Cox regression. Results Median patient age was 52 years (21–79); the majority were hormone receptor positive/HER2 negative (72 [66%]) or hormone receptor positive/HER2 positive (20 [18%]). At a median follow-up of 29 months, median TTP was 20 months (95% CI 16–26) and median survival was 49 months (95% CI 40–NR). RS were generated for 101 (93%) primary tumor samples; 22 (23%) low risk (<18), 29 (28%) intermediate risk (18–30); and 50 (49%) high risk (≥31). For all patients, RS was associated with TTP (p=0.01) and 2-year OS (p=0.04). In multivariate Cox models among estrogen receptor positive/HER2 negative patients (n=69), RS was independently prognostic for TTP (hazard ratio 1.40, 95% CI 1.05–1.86, p=0.02) and 2-year OS (hazard ratio 1.83, 95% CI 1.14–2.95, p=0.013). Conclusion The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER positive/HER2 negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in clinical management of this patient subset.

The 21-gene recurrence score — biology remains at the forefront

“…Indeed, the exploratory analysis suggested that, among the patients who received endocrine therapy, the outcomes were worse for those with high RS compared with those with low or intermediate RS. The median TTP for patients who received endocrine therapy was 15 months in the high-RS group compared with not reached and 25 months in the low-RS and intermediate-RS groups, respectively (P = 0.007) whereas, for patients who received chemotherapy, no difference in outcomes was observed among RS groups (P = 0.61) 3 . Thus, the authors speculated that a high-RS might be a predictor of resistance to endocrine therapy in patients with ER-positive metastatic breast cancer 3 .…”

“…Klein and colleagues 10 have developed a series of algorithms, the 'Magee equations' , to predict the 21-gene RS using only standard histopathological features that have high concordance, particularly in the low-risk and high-risk groups. These equations might help to determine the best course of initial therapy, not only for patients in geographical areas with limited resources, but also for those with advanced-stage disease -a setting described by King and colleagues 3 . In an era of burgeoning oncology costs, the current data 3,4 suggest that expenditure can be reduced by using the 21-gene assay to avoid administering unneces sary chemotherapy.…”

“…In the TBCRC 013 study, King et al 3 undertook a prospective registry to evaluate the role of median TTP was not reached in the patients with a low RS who were treated with endocrine therapy, compared with a median TTP of 15 months in those with high RS 3 . Indeed, the exploratory analysis suggested that, among the patients who received endocrine therapy, the outcomes were worse for those with high RS compared with those with low or intermediate RS.…”

“…In 109 patients, the 21-gene RS was calculated based on analysis of tissue from the breast primary tumour; the time to first progression (TTP) and 2-year overall survival were subsequently correlated with the RS. With a median follow-up duration of 29 months, the median TTP was 20 months (95% CI 16-26 months) and the median overall survival was an impressive 49 months (95% CI 40 months-not reached) 3 . For the entire cohort, a high RS was negatively associated with TTP and 2-year overall survival (P = 0.010 and P = 0.035 for patients with low and intermediate RS, respectively).…”

“…For the entire cohort, a high RS was negatively associated with TTP and 2-year overall survival (P = 0.010 and P = 0.035 for patients with low and intermediate RS, respectively). Patients with ER-positive, HER2-negative disease (n = 69) represented the population of greatest interest in this study; 71% of these patients received first-line endocrine therapy, whereas the remaining 29% received frontline chemotherapy 3 . The proportion of the ER-positive, HER2-negative patient group with a low (<18), intermediate (18-30) and high (≥31) RS was 32%, 38% and 30%, respectively 3 , closely mirroring the RS distribution in popu lations of patients with early stage breast cancer 1 .…”