Abstract P6-08-10: Prospective study of the impact of the Prosigna™ assay on adjuvant clinical decision-making in women with estrogen receptor-positive, HER2-negative, node-negative breast cancer: A GEICAM study
Authors: Martín Miguel , González-Rivera Milagros , Morales Serafín , de la Haba Juan , González-Cortijo Lucía , Manso Luis , Albanell Joan , González-Martín Antonio , González Sónia , Arcusa Angels , de la Cruz-Merino Luis , Rojo Federico , Vidal Maria , Goicoechea Uxue , Galván Patricia , Caballero Rosalía , Carrasco Eva , Michalopoulos Steven , Hornberger John , Prat Aleix 
Published: May 2015

Abstract
Background: Prosigna™ (PAM50) is a standardized test that measures the expression levels of 50 classifier genes in formalin-fixed paraffin-embedded (FFPE) breast tissue tumor samples. It provides subtype classification based on the fundamental biology of an individual patient’s tumor (referred to as "intrinsic subtyping"), as well as a prognostic score (referred to as "risk of recurrence [ROR] score") that predicts the probability of distant recurrence over 10 years. This decision impact study examines whether the Prosigna™ test influences both physician and patient adjuvant treatment selection, beyond standard immunohistochemistry (IHC) testing.
Methods: The analytic sample was comprised of postmenopausal women with node-negative, estrogen-receptor positive (ER+), HER2 negative (HER2-), early-stage breast cancer with tumors &lt;5 cm (T1-T2). FFPE surgical specimens were analyzed using Prosigna™ in a central laboratory. Patients were classified according to the intrinsic tumor subtype (i.e., Luminal A, Luminal B, HER2-enriched, basal-like) and ROR score (low, intermediate or high risk groups). The primary endpoint was the effect of the Prosigna™ test on oncologists’ treatment recommendations, and the actual treatment received by patients (hormonal therapy [HT], chemotherapy [CT], chemotherapy and hormonal therapy [CHT]). All samples were analyzed in two independent laboratories to measure site-to-site concordance. Prosigna™ subtypes were compared with IHC intrinsic subtypes based on the St. Gallen 2013 criteria (cut-points: PgR≥20% and Ki67≥14%).
Results: A total of 200 patients met eligibility criteria and were enrolled in the study between June 2013 and January 2014. According to Prosigna™ results, intrinsic tumor subtypes of these patients were distributed as follows: 129 Luminal A (64.5%), 66 Luminal B (33.0%), 3 HER2-enriched (1.5%) and 2 basal-like (1.0%). Modifications to the adjuvant treatment recommendations by ROR score can be seen in the following table:
Change in physician pre- to post- Prosigna recommendation Low ROR (N=101), N (%)Intermediate ROR (N=66), N (%)High ROR (N=33), N (%)TOTAL (N=200), N (%)HT to CHT0 (0.0)8 (12.1)10 (30.3)18 (9.0)CHT to HT11 (10.9)9 (13.6)0 (0.0)20 (10.0)TOTAL11 (10.9)17 (25.7)10 (30.3)38 (19.0)
Treatment decisions changed for 19.0% of all patients: 10.0% and 9.0% of patients went from CHT to HT and HT to CHT, respectively. The percentage of patients who received chemotherapy in the low, intermediate and high risk groups was 5%, 36% and 88%, respectively. Both the central and each local laboratory analyzed the samples using IHC. We found 60% concordance between central IHC and Prosigna™ intrinsic subtypes (Kappa=0.2365). Prosigna™ results were consistent across labs (Kappa = 0.89).
Conclusions: The Prosigna™ test can be reliably performed in hospital laboratories to provide useful information beyond standard clinical-pathological variables that oncologists can use to optimize adjuvant treatment decisions in clinical practice. Subtype determined using IHC is not an interchangeable proxy for subtype determined by Prosigna™.
*Two last authors have contributed equally to the study.
Citation Format: Miguel Martín, Milagros González-Rivera, Serafín Morales, Juan de la Haba, Lucía González-Cortijo, Luis Manso, Joan Albanell, Antonio González-Martín, Sónia González, Angels Arcusa, Luis de la Cruz-Merino, Federico Rojo, Maria Vidal, Uxue Goicoechea, Patricia Galván, Rosalía Caballero, Eva Carrasco, Steven Michalopoulos, John Hornberger, Aleix Prat. Prospective study of the impact of the Prosigna™ assay on adjuvant clinical decision-making in women with estrogen receptor-positive, HER2-negative, node-negative breast cancer: A GEICAM study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-10.