Abstract P3-11-10: Prosigna prognostic signature in pN1mi, estrogen receptor-positive breast cancer:the pN categorization impacts the BC risk stratification

Abstract

Background Several validated molecular subtyping tests for breast cancer based on gene expression profiling are now routinely used in clinical practice.The Prosigna® breast cancer (BC) prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The assay uses the 50-gene expression profile, weighted together with clinical variables, to generate a risk category and numerical score. The score is reported on a 0-100 scale, for hormone receptor positive BC. Prosigna test results classified tumors according to intrinsic subtypes (Lum A, Lum B, HER2-enriched, basal-like) and ROR risk groups (low risk, 0-40; intermediate risk, 41-60; and high risk, 61-100). For node-positive patients, the weight given to the node status is similar when considering pN1mi ([0.2-2mm]) or pN1 (>2mm, 1-3 positive lymph nodes). Our aim was to characterize the Prosigna test classification of the pN1mi subgroup in the French national registry for molecular signatures in ER+ BC. Methods Since 2018, four French laboratories using Prosigna test in clinical practice retrospectively implement a national registry for molecular prognostic signatures in ER+ BC. We analyzed the pN1mi subgroup with regards to their clinico-pathological characteristics, Prosigna test results and ROR risk score. Using the definition formula of the prosigna algorithm, we could calculate a hypothetical score if the pN1mi has been considered as pN0 and redefine risk categories for pN1mi breast cancers. Results The database included 886 tests performed in routine practice, including 91 (10.3%) pN1mi. The pN1mi BC were ER+ HER2- (88/91, 96.7%), invasive carcinoma of no special type in 81/91 (89%), with a median tumor size of 23 mm (range 12-60). Among these, the median ROR score was 44, and 51/91 tumors (56%) were classified as LumA tumors, 34/91 (41%) as LumB, two asHER2-enriched and one as basal-like. Interestingly, the probability of distant recurrence was 26% if pN1mi BC were considered as N+ but lowered to 10% if considered as pN0. Among the different molecular subtypes, the change from pN1 top N0 has different weight: in Lum A tumors, the switch in the probability of distant recurrences was 13 to 6% according to pN categorization of the pN1mi BC, and the median ROR score moved from 27 to 6 with 15/51(29%) of Lum A tumors considered as high risk if pN1 but only 1/51 if pN0; 31/51 (61%) versus 14/51 (27.5%) were in the intermediate risk group, and only 5/51 (10%) versus 34 (67%) in the low risk group. For LumB tumors, the switch in the probability of distant recurrences was 29% to 17% according to pN categorization and and the median ROR score moved from 60 to 15 with 36/37(97.3%) of Lum B tumors considered as high risk if pN1but only 13/37(35%) ifp N0; 1/37 versus 20/37 (54%) were in the intermediate risk group, and none of the 37 LumB versus 1 in the low risk group. Conclusion With regards to Prosigna test in pN1mi BC - and the persistent debate as to whether they should bear the same weight as pN1 pN0 tumors - categorization in ROR risk group is likely to be impacted by the node factor weight, and more importantly among Lum B tumors. Citation Format: Charafe-Jauffret E, Duprez-Paumier R, Berghian A, Penault-Llorca F, Dauplat MM, Boucraut A, Cohen M, Houvenaeghel G, Maroc C, Pradines A, Cayre A, Etancelin P, Lacroix-triki M. Prosigna prognostic signature in pN1mi, estrogen receptor-positive breast cancer:the pN categorization impacts the BC risk stratification [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-10.