Abstract PD5-03: TransNEOS: Validation of the oncotype DX recurrence score (RS) testing core needle biopsy samples from NEOS as predictor of clinical response to neoadjuvant endocrine therapy for postmenopausal estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer patients
Authors: Yamamoto Y , Iwata H , Masuda N , Fujisawa T , Toyama T , Kashiwaba M , Ohtani S , Taira N , Sakai T , Hasegawa Y , Nakamura R , Akabane H , Shibahara Y , Sasano H , Yamaguchi T , Sakamaki K , Chao C , McCullough D , Sugiyama N , Ohashi Y 
Published: February 2018

Abstract
Background: Neoadjuvant therapy for locally advanced breast cancer has the potential to improve surgical therapeutic outcomes without sacrificing the survival advantages of adjuvant therapy. However, determining whether ER+ patients (pts) will respond to neoadjuvant (NA) chemotherapy (CT) or hormone therapy (HT) can be difficult. Not all ER+ pts respond to NACT, while response to NAHT can vary across ER+ pts. Thus, the ability to select pts more likely to benefit from NAHT would represent progress in clinical management of breast cancer. NEOS is a randomized phase III study assessinglong-term prognosis of ER+ primary breast cancer with/without adjuvant CT following NAHT (UMIN 000001090, http://www.umin.ac.jp/). We used archived core biopsy tumor samples from the NEOS study to validate the RS result as a predictor of clinical response and its association with successful breast conserving surgery (BCS) in pts treated with 6 months of NAHT.
Methods: NEOS enrolled 904 postmenopausal pts with ER+, HER2-, clinically node negative (cN0) breast cancer to evaluate whether adjuvant CT was necessary for pts who responded to NAHT. In this current study, we enrolled pts with tumors ≥2cm from the NEOS study. Biopsy samples of 333 pts were assessed for the Oncotype DX assay. Response to NAHT was recorded as complete/partial response (CR/PR), or stable/progressive disease (SD/PD).
Primary endpoint of this study was to evaluate clinical response (CR/PR) to NA letrozole between pts with low (&lt;18) and high (≥31) RS result. Secondary endpoints include evaluating the relationships between clinical response and continuous RS results, and other covariates including age, tumor size, grade, Ki67 by IHC, ER and PR single gene scores, and ER and proliferation gene group scores by RT-PCR.
Results: The analysis included 294 pts with median age of 63 yrs, median tumor size of 25mm, and 66% were nuclear grade 1. 156 (53.0%), 83 (28.6%) and 54(18.4%) cases were low, intermediate, and high RS groups by Oncotype DX, respectively. Six (2%), 126 (42.8%), 149 (50.3%), 13 (4.4%) cases experienced CR, PR, SD, PD as clinical response, respectively, similar to that of all NEOS pts. Clinical response rate was 54%, 42% and 22% in low, intermediate, and high RS groups, respectively. The proportion of pts with clinical response was significantly higher in the low RS group vs the high RS group (p&lt;0.001). In univariate analyses, continuous RS was significantly associated with clinical response (p&lt;0.001), along with ER (p=.02), PR (p&lt;0.001), and ER gene group score (p&lt;0.001). Other covariates were not associated with clinical response.
Conclusion: The Oncotype DX RS test in core biopsy samples is validated as a predictive assay for clinical response of NAHT in postmenopausal, ER+/HER2-, cN0, primary early breast cancer pts. Further results on the association of RS results with BCS outcomes following NAHT will be presented. These results when combined with previously published data on RS in NACT studies help guide pts with ER+, HER2- breast cancer with NAHT vs NACT treatment options to maximize clinical response.
Citation Format: Yamamoto Y, Iwata H, Masuda N, Fujisawa T, Toyama T, Kashiwaba M, Ohtani S, Taira N, Sakai T, Hasegawa Y, Nakamura R, Akabane H, Shibahara Y, Sasano H, Yamaguchi T, Sakamaki K, Chao C, McCullough D, Sugiyama N, Ohashi Y. TransNEOS: Validation of the oncotype DX recurrence score (RS) testing core needle biopsy samples from NEOS as predictor of clinical response to neoadjuvant endocrine therapy for postmenopausal estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer patients [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 PD5-03.