Molecular characterization by the 21-gene breast cancer (BC) Recurrence Score (RS) test of BRCA1/2 mutation carriers (mBRCA1/2) versus the general BC patient (pt) population

BackgroundThe RS assay is a validated test used to guide treatment decisions in ER+ HER2-negative early-stage BC. We compared RS distribution and expression of the single genes/gene groups within this assay between mBRCA1/2 carriers ER+ HER2-negative BC pts vs the general BC pt population undergoing RS testing.MethodsThis retrospective cohort study included consecutive female ER+ HER2-negative BC pts with germline mBRCA1/2 who were RS-tested in 2004-2015. Their RS and gene expression data were compared to the commercial use database (DB) described by Jakubowski et al (J Surg Oncol. 2020;122:611). Chi-square test and 1-sample t-test were used to compare RS distribution and single gene/gene group scores, respectively, between the cohort and the DB.ResultsTable: 152PmBRCA1/2 carriers N = 81Commercial use DB N = 799,986PRS group, %0-109%22%<.000111-2542%62%26-10049%16%Gene expression, mean (SD)ER groupESR9.8 (1.4)10.0NSPGR6.3 (1.7)7.3<.0001BCL28.6 (1.0)8.5NSSCUBE28.2 (1.8)8.8.0023Group score8.0 (1.1)8.5<.0001Proliferation groupCCNB15.9 (0.5)5.7.0001KI677.1 (0.8)6.4<.0001STK156.4 (0.8)5.6<.0001SURV6.1 (1.1)5.0<.0001MYBL25. 6 (1.0)4.5<.0001Group score6.2 (0.7)5.4<.0001HER2 groupERBB29.1 (0.7)9.2NSGRB76.8 (0.7)6.7.049Group score7.1 (0.7)6.9NSInvasion groupSTMY39.8 (1.4)10.0NSCTSL24.4 (0. 9)3.8<.0001Group score7.1 (0.8)6.9.043IndividualCD689.0 (0.6)8.8.0070GSTM16.9 (1.4)7.8<.0001BAG18.2 (0.6)8.5.0001 Open table in a new tab ConclusionsmBRCA1/2 carriers are characterized by higher RS results that stem from a distinct gene expression profile of most genes in the RS assay.Legal entity responsible for the studyYerushalmi, Kaduri.FundingOncotest, Exact Sciences.DisclosureR. Yerushalmi: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Medison, MSD, AstraZeneca, Eli Lilly; Financial Interests, Personal, Principal Investigator: Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Role: Roche, Novartis, Medison, AstraZeneca, Gilead, Eli Lilly, Pfizer. S. Paluch-Shimon: Financial Interests, Personal, Advisory Role: Roche, Novartis, Eli Lilly, Gilead, MSD, Pfizer, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Exact Sciences, NanoString, Novartis; Financial Interests, Personal, Speaker’s Bureau, And travel: Roche; Financial Interests, Personal, Speaker’s Bureau, and travel: Pfizer. L. Soussan-Gutman: Financial Interests, Personal, Full or part-time Employment: Oncotest, Genomic Health. F.L. Baehner: Financial Interests, Personal, Full or part-time Employment: Exact Sciences; Financial Interests, Personal, Stocks/Shares: Exact Sciecnes. H. Voet: Financial Interests, Personal, Advisory Role: BioInsight. A. Bareket-Samish: Financial Interests, Personal, Writing Engagements: Exact Sciences, Can-Fite BioPharma Ltd, Pfizer, Oncotest, Teva. L. Kaduri: Financial Interests, Personal, Research Grant: Hoffman la roche; Financial Interests, Personal, Principal Investigator: Eli Lilly , Bayer , Novartis . All other authors have declared no conflicts of interest. BackgroundThe RS assay is a validated test used to guide treatment decisions in ER+ HER2-negative early-stage BC. We compared RS distribution and expression of the single genes/gene groups within this assay between mBRCA1/2 carriers ER+ HER2-negative BC pts vs the general BC pt population undergoing RS testing. The RS assay is a validated test used to guide treatment decisions in ER+ HER2-negative early-stage BC. We compared RS distribution and expression of the single genes/gene groups within this assay between mBRCA1/2 carriers ER+ HER2-negative BC pts vs the general BC pt population undergoing RS testing. MethodsThis retrospective cohort study included consecutive female ER+ HER2-negative BC pts with germline mBRCA1/2 who were RS-tested in 2004-2015. Their RS and gene expression data were compared to the commercial use database (DB) described by Jakubowski et al (J Surg Oncol. 2020;122:611). Chi-square test and 1-sample t-test were used to compare RS distribution and single gene/gene group scores, respectively, between the cohort and the DB. This retrospective cohort study included consecutive female ER+ HER2-negative BC pts with germline mBRCA1/2 who were RS-tested in 2004-2015. Their RS and gene expression data were compared to the commercial use database (DB) described by Jakubowski et al (J Surg Oncol. 2020;122:611). Chi-square test and 1-sample t-test were used to compare RS distribution and single gene/gene group scores, respectively, between the cohort and the DB. ResultsTable: 152PmBRCA1/2 carriers N = 81Commercial use DB N = 799,986PRS group, %0-109%22%<.000111-2542%62%26-10049%16%Gene expression, mean (SD)ER groupESR9.8 (1.4)10.0NSPGR6.3 (1.7)7.3<.0001BCL28.6 (1.0)8.5NSSCUBE28.2 (1.8)8.8.0023Group score8.0 (1.1)8.5<.0001Proliferation groupCCNB15.9 (0.5)5.7.0001KI677.1 (0.8)6.4<.0001STK156.4 (0.8)5.6<.0001SURV6.1 (1.1)5.0<.0001MYBL25. 6 (1.0)4.5<.0001Group score6.2 (0.7)5.4<.0001HER2 groupERBB29.1 (0.7)9.2NSGRB76.8 (0.7)6.7.049Group score7.1 (0.7)6.9NSInvasion groupSTMY39.8 (1.4)10.0NSCTSL24.4 (0. 9)3.8<.0001Group score7.1 (0.8)6.9.043IndividualCD689.0 (0.6)8.8.0070GSTM16.9 (1.4)7.8<.0001BAG18.2 (0.6)8.5.0001 Open table in a new tab ConclusionsmBRCA1/2 carriers are characterized by higher RS results that stem from a distinct gene expression profile of most genes in the RS assay. mBRCA1/2 carriers are characterized by higher RS results that stem from a distinct gene expression profile of most genes in the RS assay.