Abstract P1-07-16: Retrospective analysis of oncotype DX recurrence score (RS) and discordance in patients with node-negative, ER+ breast cancer with recurrence
Authors: Zimmerman BS , Cascetta KP , Ru M , Eggert L , Molot MC , Nayak A , Bleiweiss I , Tiersten A 
Published: February 2018

BACKGROUND: Oncotype RS is a 21-gene assay used to predict the likelihood of distant recurrence and benefit of chemotherapy in patients with node-negative, tamoxifen treated breast cancer. We developed a database to determine tumor recurrence rates and identify cases of discordance between Oncotype RS and tumor grade (TG). Our goal was to recognize patients with discordant tumors who had breast cancer recurrence and to understand the implications for patient management.

METHODS/RESULTS: We analyzed patient and tumor characteristics from 704 breast cancer patients between 2006-2016. Of these patients, there were thirteen recurrences (n=13), or 1.9% recurrence rate at a median follow-up of 4.2 years. When stratified by RS, recurrence rates were 1%, 2.4% and 4.3% in low, intermediate and high-risk groups respectively. Of the 13 patients who recurred, 31% had a low RS (&lt;18), 54% had an intermediate RS (18-30) and 15% had a high RS (&gt;31). The median RS was 23 and median age at time of recurrence was 55 years (62% postmenopausal). Tumor characteristics at time of recurrence were notable for: 77% metastatic, 23% locally recurrent, 85% PR positive, 69% moderately-differentiated (MD) and 31% poorly-differentiated (PD). No well-differentiated (WD) tumors recurred.

We defined Oncotype discordance as either 1-step or 2-step difference between Oncotype risk group (low, intermediate, high) and tumor grade (WD, MD, PD). Prior studies have demonstrated 7-19% “2-step discordance” between TG and RS (i.e. PD tumors with low-risk RS or WD tumors with high-risk RS). Of the 13 recurrences in our database, 46% were at least 1-step discordant, compared with 64.3% in our overall database. Among these recurrences, we compared discordant versus concordant tumors using two-sided T-tests. We found that fewer patients were treated with systemic chemotherapy in the discordant group (p=0.045), which was statistically significant. Among discordant patients, only one received chemotherapy, though all displayed MD or PD tumor grade. Discordant tumors tended to have lower RS (mean 17 vs. 27, p=0.34) and tended to be larger (mean 1.88cm vs. 1.33cm), however this was not statistically significant (p=0.84). Notably, the two largest tumors were both discordant. There were no significant differences in terms of age, Oncotype ER/PR score or mitotic count.

CONCLUSION: Although the sample size of recurrent patients is small, our data may suggest that patients with discordant tumors of low-risk Oncotype RS but higher TG may be receiving inadequate treatment (i.e. no chemotherapy). In addition to RS, other factors such as discordance, TG and tumor size should perhaps be considered when determining treatment plans.

Characteristics of Breast Cancer Recurrences in Oncotype DX DatabaseSubject #Age (years)Oncotype RSTumor GradeDiscordancePath PR%Tumor Size (cm)Chemotherapy14111MDY600.9N25811MDY1001.7N35713MDY301.0N45515MDY902.7N56122MDN301.5Y64522MDN901.8Y75323MDN00.9N83324MDN951.4Y96324PDY802.9U104129MDN801.1Y116530PDY102.1Y124933PDN01.6Y136135PDN51.0YMD=moderately-differentiated, PD=poorly-differentiated, Y=Yes, N=No, U=Unknown

Citation Format: Zimmerman BS, Cascetta KP, Ru M, Eggert L, Molot MC, Nayak A, Bleiweiss I, Tiersten A. Retrospective analysis of oncotype DX recurrence score (RS) and discordance in patients with node-negative, ER+ breast cancer with recurrence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-16.