Abstract PS15-18: Clinical utility of genomic testing for early stage breast cancer patients treated with APBI brachytherapy
Authors: Diaz Roberto , Mills Matthew N , Nanda Ronica H , Stout Lisa L , Dube Scott , Altoos Taghrid A , Wilson Jason P , Allen Kathleen G , Baginski Jolanta L , Blumencranz Peter W 
Published: February 2021

Background: Adjuvant radiation after breast conserving surgery (BCS) remains the standard of care for management of patients with early-stage breast cancer (ESBC). Whole breast irradiation (WBI) after lumpectomy for ESBC has demonstrated a 50% reduction in the 10-year rate of recurrence (ROR). NSABP B-39 determined that accelerated partial-breast irradiation (APBI) was effective at reducing the ROR by treating ESBC directly at the tumor bed and that a rigorous course of WBI may not be necessary in select patients. In this study, we determined the impact of genomics and tumor biology on the decision to escalate or de-escalate therapies and on subsequent outcomes beyond anatomic staging for APBI patients. Methods: This analysis included 91 patients with biopsy confirmed invasive ESBC treated with BCS followed by APBI intracavitary brachytherapy at a dose of 34.0 Gy in 10 fractions from 2007 to 2018 who received either MammaPrint (MP) or Oncotype DX (ODx) testing. Clinicopathological risk assessment was performed using MINDACT criteria for clinical guidelines to classify patients as either clinical low risk (CLR) or clinical high risk (CHR). MP stratified patients into either MP Low Risk (MLR) or MP High Risk (MHR). ODx was used with TAILORx-defined cutoffs to stratify patients into either ODx Low Risk (OLR), which is women &gt;50 years of age with HR+, HER2-negative, node-negative breast cancer, Recurrence Score (RS) of 0 to 25 or ODx High Risk (OHR), RS 26-100. If both methods were concordant, the genomic test could not be determined to have impacted the treatment decision. Clinical utility was established in discordant cases when the genomic test guided treatment. Differences in overall survival (OS) were assessed by Kaplan Meier analysis and log-rank test. Relevant clinical data was abstracted from the electronic medical record. Results: Patients (n=91) were 60% CLR and 40% CHR. Of the CLR patients with MP testing, 36% reclassified as MHR; 25% of these (3/12) omitted chemotherapy (CT) despite the discordant result, one of whom (33%) had a local recurrence within 0.25 years of follow-up (FU). Of CHR patients, 54% were MHR, 62% of whom received CT in line with the CHR/MHR result. Of the CHR patients who reclassified as MLR (46%), 91% omitted CT from treatment plans, in alignment with MP results. There were no distant or local recurrences or deaths to date in these groups. About 96% of CLR patients were OLR with 2 events (BC related death). One patient that reclassified as OHR omitted CT despite a discordant CLR/OHR result and has not had a recurrence within 3.9 years of FU. Of the CHR patients who reclassified as OLR (83%), 90% omitted CT in alignment with ODx results; 22% of whom had distant metastases and subsequent death within 1.1 years of FU. Conclusion: 9/11 (82%) of Oncotype discordant patients followed the genomic test recommendation, of whom 22% could not safely do so without impairing outcome. 19/23 (83%) of MammaPrint discordant patients all safely followed this genomic test recommendation. These data suggest that the addition of a genomic signature may allow de-escalation of radiotherapy to APBI even in select high risk patients, provided they follow the systemic therapy recommended by the genomic test result.

CLR/MLR (n=21)CHR/MLR (n=11)CLR/MHR (n=12)CHR/MHR (n=13)Followed MP YES21 (100%)10 (91%)9 (75%)8 (62%)Followed MP NO01 (9%)3 (25%)5 (38%)EVENT001 LRR03-year OS (95% CI)100%100%100%100%CLR/OLR (n=23)CHR/OLR (n=10)CLR/OHR (n=1)CHR/OHR (n=2)Followed ODx YES19 (83%)9 (90%)02 (100%)Followed Odx NO4 (17%)1 (10%)1 (100%)0EVENT2 Deaths at 6.3 and 7.9 years2 Deaths at 0.5 and 1.7 years01 Death at 6.5 years(RS 21 & 25)(RS 17 & 23)(RS 32)3-year OS (95% CI)100%77.8% (36.5-93.9)100%100%

Citation Format: Roberto Diaz, Matthew N Mills, Ronica H Nanda, Lisa L Stout, Scott Dube, Taghrid A Altoos, Jason P Wilson, Kathleen G Allen, Jolanta L Baginski, Peter W Blumencranz. Clinical utility of genomic testing for early stage breast cancer patients treated with APBI brachytherapy [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 PS15-18.