Abstract PD4-08: Does genomic recurrence score predict for ipsilateral breast tumor recurrence after breast conservation therapy?
Authors: Richman Adam H , Patel Ankur K , Soran Atilla , Diego Emilia J , McAuliffe Priscilla F , Johnson Ronald R , Brufsky Adam , Gorantla Vikram , Steiman Jennifer , Lee Joanna S , Beriwal Sushil 
Published: February 2021

Purpose/ObjectivesGene profiling Recurrence Score (RS) assays are commonly used to identify patients with hormone receptor (HR) positive, HER-2 negative invasive breast cancer (IBC) who might benefit from systemic chemotherapy. More recently, the 21-gene recurrence score assay has been found to correlate with locoregional recurrence (LRR) after mastectomy (SWOG) or lumpectomy (NSABP). In the NSABP analysis, risk of ipsilateral breast tumor recurrence (IBTR) was not correlated with RS and was high in patients younger than 50 years of age irrespective of genomic score. However, tumor bed radiotherapy (RT) boost was not utilized in these protocols. The purpose of this study is to determine if RS predicts for IBTR or LRR in women treated with modern breast conserving therapy (BCT) using RT boost and optimal systemic treatment.

Materials/MethodsWe performed a retrospective review of patients with HR positive, HER-2 negative IBC who underwent gene profile testing and were treated at our institution with BCT and sentinel lymph node biopsy (SLNB) from 2013 to 2017. Both node negative and node positive patients were included. The Oncotype® 21-gene recurrence score assay was used in 84%, Mammaprint® in 12%, and Prosigna® in 4%. 97% received hormonal therapy (HT), 18% chemotherapy (CHT), 58% hypofractionated RT, and 96% a surgical bed RT boost. IBTR and LRR were measured from the end of local treatment to IBTR or LRR, with death or last follow up date as censoring events. The Kaplan-Meier method was used to estimate event-time probabilities for the above endpoints. Predictors of IBTR/LRR were analyzed using log rank tests between groups and with Cox regression for continuous variables. P-values &lt;0.05 were considered significant.

Results 686 evaluable patients were identified with median follow-up of 50 months (Interquartile range [IQR] 36-64 months). Median age was 61 years (IQR 53-68 years). 76% had invasive ductal carcinoma, 64% grade 2 disease, and 18% positive SLNB. RS of any type was low in 60% of patients and intermediate or high in 40%. Four-year IBTR was 0.2% (95% Confidence Interval [CI] 0.0-0.6%) for any low risk RS and 1.6% (95% CI 0.0 - 3.2%) for intermediate or high-risk RS (p = 0.01). Tumor grade was also predictive for IBTR (p &lt; 0.01), but age &lt; 50 was not (p = 0.4). For patients younger than 50, four-year IBTR was 0.9% (95% CI 0.0 - 2.6%) and not affected by RS (p = 0.231). On multivariate analysis, grade remained a significant predictor for IBTR (p = 0.04), but RS did not (p = 0.08). Four-year LRR was 0.5% (95% CI 0.0-1.3%) in patients with a low risk RS and 3.8% (95% CI 1.3-6.3%) in those with intermediate or high risk (p &lt; 0.01). Grade (p &lt; 0.01) and pathologic tumor size (p &lt; 0.01) were also correlated with LRR, although only RS (HR 5.14, 95% CI 1.02-25.9, p = 0.047) and pathologic tumor size on (HR 1.05, 95% CI 1.01- 1.09, p = 0.02) remained significant on multivariate analysis. Of the 125 patients with positive SLNB, 47% were treated with high tangents and 42% with comprehensive regional nodal irradiation. For node positive patients, LRR was not correlated with low versus intermediate or high RS (p = 0.07). However, if intermediate risk Oncotype scores were grouped with low risk Oncotype and Mammaprint scores, then LRR was 0.0% for low and intermediate risk and 9.1% for high risk (p &lt; 0.01).

ConclusionsIn this large single institution study, RS did not predict for IBTR in patients with HR positive, HER-2 negative invasive breast cancer in any age group treated with BCT utilizing a surgical bed RT boost and optimal systemic treatment. High RS did predict for high LRR because of higher regional recurrences and can be used as a guide to add comprehensive RT for node positive patients after BCT.

Citation Format: Adam H Richman, Ankur K Patel, Atilla Soran, Emilia J Diego, Priscilla F McAuliffe, Ronald R Johnson, Adam Brufsky, Vikram Gorantla, Jennifer Steiman, Joanna S Lee, Sushil Beriwal. Does genomic recurrence score predict for ipsilateral breast tumor recurrence after breast conservation therapy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-08.