Abstract 152P
Background
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.
Methods
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.
Results
The mBRCA1/2 cohort included 81 pts; the DB included 799,986 BC samples. Age at diagnosis was younger in the mBRCA1/2 cohort vs the DB (median [IQR], 56 [47-61.5] vs 60 [51-67] yrs; P<.0001). In the mBRCA1/2 cohort, RS distribution shifted towards the high RS category (Table). Expression of 12 of the 16 cancer genes in the RS assay and the ER, proliferation, and invasion gene group scores differed significantly between the mBRCA1/2 cohort and the DB, all in a direction that contributed to higher RS results (Table). Table: 152P
| mBRCA1/2 carriers N = 81 | Commercial use DB N = 799,986 | P | |
| RS group, % | |||
| 0-10 | 9% | 22% | <.0001 |
| 11-25 | 42% | 62% | |
| 26-100 | 49% | 16% | |
| Gene expression, mean (SD) | |||
| ER group | |||
| ESR | 9.8 (1.4) | 10.0 | NS |
| PGR | 6.3 (1.7) | 7.3 | <.0001 |
| BCL2 | 8.6 (1.0) | 8.5 | NS |
| SCUBE2 | 8.2 (1.8) | 8.8 | .0023 |
| Group score | 8.0 (1.1) | 8.5 | <.0001 |
| Proliferation group | |||
| CCNB1 | 5.9 (0.5) | 5.7 | .0001 |
| KI67 | 7.1 (0.8) | 6.4 | <.0001 |
| STK15 | 6.4 (0.8) | 5.6 | <.0001 |
| SURV | 6.1 (1.1) | 5.0 | <.0001 |
| MYBL2 | 5. 6 (1.0) | 4.5 | <.0001 |
| Group score | 6.2 (0.7) | 5.4 | <.0001 |
| HER2 group | |||
| ERBB2 | 9.1 (0.7) | 9.2 | NS |
| GRB7 | 6.8 (0.7) | 6.7 | .049 |
| Group score | 7.1 (0.7) | 6.9 | NS |
| Invasion group | |||
| STMY3 | 9.8 (1.4) | 10.0 | NS |
| CTSL2 | 4.4 (0. 9) | 3.8 | <.0001 |
| Group score | 7.1 (0.8) | 6.9 | .043 |
| Individual | |||
| CD68 | 9.0 (0.6) | 8.8 | .0070 |
| GSTM1 | 6.9 (1.4) | 7.8 | <.0001 |
| BAG1 | 8.2 (0.6) | 8.5 | .0001 |
Conclusions
mBRCA1/2 carriers are characterized by higher RS results that stem from a distinct gene expression profile of most genes in the RS assay.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Yerushalmi, Kaduri.
Funding
Oncotest, Exact Sciences.
Disclosure
R. 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.