PD06-01: Molecular Classification with 21 Gene Assay (Oncotype DX®) Shows in 196,967 ER Positive Patients High Frequency of Low Recurrence Score [LRS] in Both Node Positive (N+) and Negative (N-) Breast Cancer (BrCa) Cohorts. Definition of Chemoresistance Based on LRS with Cost and Guideline Implications.

Abstract

Abstract BACKGROUND : Key retrospective analyses have shown no benefit from adjuvant CT [CT] in ER+, N-ve and N+ve BrCa pts with LRS by Oncotype DX assay. (For N-ve, hazards [RR] = 1.31, 95% C.I.: 0.46, 3.78 (Paik et.al., 2006); for N+ve, RR=1.01, 95% C.I.: 0.54, 1.93 (Albain et.al. 2009)]. LRS (RS<18) can therefore be equated to CT resistance (CTRES). OBJECTIVES : 1. To determine the frequency of CTRES determined by Oncotype DX in the Genomic Health database of ER+, N-ve and N+ve pts. 2. To estimate the net cost savings resulting from avoidance of CT for CTRES pts, based on universal Oncotype DX testing in ER+ pts being considered for CT. METHODOLOGY STEP 1 : Oncotype DX results were analyzed according to nodal status in the 196,967 ER+ tumor samples for CT candidates submitted to Genomic Health between Jan 2007 - Apr 2011. STEP 2 : We then calculated the $ cost saved, result of Oncotype DX, assuming: i. of new BrCa pts, 42% could be candidates Oncotype DX and CT (ER+, high risk N-ve; and all ER+ N+ve) ii. either 50% or 100% CT avoidance — according to oncology practice — among LRS cases, estimating the CT cost/pt = $15,000 US; and Oncotype DX cost/pt = $4,000 US. RESULTS — STEP 1 LRS based on Oncotype DX was more prevalent in N+ pts (chi sq p <0.0001) RESULTS — STEP2 ; CT Cost [in millions, USD] / 1,000 newly diagnosed cases who are CT and Oncotype DX condidates, of whom 50% [conservative estimates] will have LRS Thus, in USA, with 225,000 new BrCa pts / year, and 94 500 [42%] candidates for Oncotype DX, over 47,250 pts will have LRS, with overall savings of $330.8 mil/year with 100% CT avoidance. In Canada, with 25,000 estimated new BrCa pts/year, corresponding savings will be $46.2 mil/year. CONCLUSIONS: 1. Low RS status, presently the most reliable CTRES biomarker, is expressed with higher frequency among N+ve (59%) vs N-ve (54%) ER+ breast cancer pts. 2. If all eligible cases had the Oncotype DX test, and all with LRS would avoid CT, close to 50,000 pts in USA, and over 5,200 in Canada will be spared ineffective CT and associated toxicity / year, with hundreds of million dollars saved each year. 3. On principles of ethics and economy, these data suggest that until new research refines the molecular classification of BrCa for higher efficacy, and with lower cost and more practical access: a. universal OncotypeDx testing for pts should be performed for all ER+ breast cancer pts candidates for CT; b. management guidelines should be changed to avoid CT in all LRS pts, irrespective of nodal status; c. until prospective randomized trials confirm CT benefit among LRS pts, its use should be considered investigational. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD06-01.