PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor–Positive Early Breast Cancer

Abstract

Purpose The PAM50-based Prosigna risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR). The value of Prosigna for predicting DR was examined in a comprehensive nationwide Danish cohort consisting of postmenopausal women with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone. Patients and Methods Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were treated with endocrine therapy for 5 years. Primary tumor blocks from 2,740 patients were tested with Prosigna and, after determination of human epidermal growth factor receptor 2 (HER2) status, data from 2,558 hormone receptor-positive/HER2-negative samples were analyzed, including 1,395 node-positive patients. Fine and Gray models were applied to determine the prognostic value of ROR for DR. Results Median follow-up for recurrence was 9.2 years. Twenty-six percent of the node-positive patients were classified as low ROR (n = 359) with a DR risk of 3.5% (95% confidence interval [CI], 1.9% to 6.1%) versus a DR risk of 22.1% (95% CI, 18.6% to 25.8%) at 10 years for patients classified as high ROR (n = 648). Node-negative patients classified as low and high ROR had a risk of DR of 5.0% (95% CI, 2.9% to 8.0%) and 17.8% (95% CI, 14.0% to 22.0%), respectively. Luminal B tumors (n = 947; DR risk, 18.4% [95% CI: 15.7% to 21.3%]) had a significantly worse outcome than luminal A tumors (n = 1,474,;DR risk, 7.6% [95% CI: 6.1% to 9.2%]; P < .001). Conclusion Prosigna ROR score improved the prediction of outcome in this nationwide Danish population. In a real-world setting, Prosigna can reliably identify node-negative patients and a significant proportion of patients with one to three positive nodes who can be spared treatment with adjuvant chemotherapy.

Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer

“…Recent days have seen models using multi-omics data to pursue better accuracy but failed in clinical transformation owing to the limitation of detection technology and standardized criteria. Meanwhile, several multi-gene test panels had already validated good utility by randomized clinical trials and been recommended by NCCN guidelines like the 21-gene test [74], MammaPrint [75] or PAM50 [76] [77]. These results demonstrated better efficacy of predictive models combined with molecular and clinical information than each alone.…”

The clinical database and implementation of treatment guidelines by the Danish Breast Cancer Cooperative Group in 2007–2016

“…Using multivariable fractional polynomials a highly performing prognostic index was constructed [12]. In 2017, risk assessment was further refined by inclusion of molecular subtypes (PAM50) [13].…”

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

“…The power of chemotherapy benefit using the Mammaprint test was tested in the MINDACT trial 2016 . Prediction of prognosis in chemotherapy‐treated patients was validated for the RS in the NASBP B28, PCAS‐01, for Prosigna in the DBCG77B trial . and for Endopredict in the GEICAM/9906 trials .…”

“…21 Prediction of prognosis in chemotherapy-treated patients was validated for the RS in the NASBP B28, PCAS-01, for Prosigna in the DBCG77B trial. 26 and for Endopredict in the GEICAM/9906 trials. 13,29,30 The prognostic power of Mammaprint in untreated patients was validated in the TRANSBIG study.…”