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542 Background: Opioid-induced immunomodulation may be of particular importance in triple negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and outcomes in a large TNBC cohort. Methods: Consecutive patients with stage I-III primary TNBC treated between 03/2010 and 12/2016 were identified from our prospectively maintained database. Total intraoperative opioid dose was extracted from anesthetic records and converted to oral morphine milligram equivalents (MME) (10 MME = 50 mcg fentanyl IV). Univariable and multivariable (MVA) Cox proportional hazards analysis (adjusting for relevant clinicopathological features, (neo)adjuvant therapy, anesthesia technique and morbidity score), were performed to quantify the association between opioid exposure and recurrence-free survival (RFS) and overall survival (OS). Results: 1143 patients were included. Median age was 54 years (IQR 45, 64). 911 (80%) had ductal histology, 359 (31%) had nodal metastases, and 1070 (94%) were poorly differentiated. 781 (68%) received adjuvant chemotherapy and 313 (27%) received neoadjuvant chemotherapy. 525 (46%) received total intravenous anesthesia and 618 (54%) had general anesthesia. Median intraoperative opioid dose was 30 MME (IQR 20, 60). 5-year RFS was 81% (95% CI 79%-84%), 5-year OS was 86% (95% CI 84%-88%). In MVA, higher opioid administration was associated with favorable RFS but did not significantly affect OS (Table). Conclusions: Our study is the first to directly evaluate intraoperative opioid administration in TNBC and suggests a protective effect on RFS. Future work will focus on elucidating the underlying mechanism for this effect, including possible modulation of endogenous opioid signaling pathways and immunologic correlates. [Table: see text]

592 Background: Checkpoint inhibition (CPI) combined with local strategies that cause local tumor destruction, such as cryo may augment tumor specific immunity and improve survival. We previously demonstrated in 18 ESBC patients (pts) that pre-operative (pre-op) cryo with ipilimumab (ipi) is not only safe but also generates robust local and systemic immune responses (NCT01502592). Given the added activity of dual CPI in other tumors, we undertook a second pilot study of pre-op ipi/nivolumab (nivo)/cryo to confirm the safety of this combination and the impact on immune biomarkers. Methods: In both pilot studies, eligible pts had operable ≥1.5cm invasive HER2 negative ESBC. CPI was administered 8-15d prior to, and cryo was performed 7-10d prior to, standard-of-care (SOC) surgery. Toxicity evaluation continued for 12wks after drug administration. Blood for immune correlates was obtained at baseline, cryo, surgery and 2-4 weeks thereafter. Tumor samples were obtained at cryo and surgery. Flow-cytometry of peripheral lymphocytes was compared to previously reported ipi/cryo responses. Results: After a median follow-up of 66 months all 18 ESBC ipi/cryo pts, including 3 TNBC pts, are recurrence free. In the ipi/nivo/cryo study, the safety primary endpoint was met when 5 pts underwent SOC surgery without delay. Ipi/nivo/cryo was well tolerated overall. One pt on an aromatase inhibitor had grade 4 liver toxicity 8 weeks after surgery. One pt, 3 weeks after her SOC surgery, developed grade 1 hyperthyroidism, preventing a secondary axillary dissection from proceeding as scheduled. Robust activation of peripheral CD4+ and CD8+ T cells peaked at week 2 post ipi/nivo with the majority of activated CD8+ T cells expressing PD1. Comparing the correlatives of the ipi/nivo/cryo study with the prior ipi/cryo study, we observed higher expression of activation markers (Ki-67, ICOS, CTLA-4, LAG-3) on peripheral T cells and downregulation of suppressor cells. Conclusions: Ipi/cryo-treated pts, including 3 TNBC pts, remain recurrence free after > 5y. Combining cryo with ipi/nivo preop is feasible, safe, and associated with greater T cell activation than ipi/cryo alone. These results informed an ongoing randomized phase 2 study of pre-op ipi/nivo/cryo versus SOC in women with residual TNBC after neoadjuvant chemotherapy (NCT03546686). Clinical trial information: NCT02833233.

TPS1101Background: Available in vitro chemosensitivity models are time consuming, difficult to scale and fail to recapitulate the complexities of the tumor microenvironment. As a result, ASCO advis...

TPS3098Background: Regulatory T cells (Treg) are a subset of CD4 T cells that preserve immune homeostasis by the establishment and maintenance of peripheral tolerance. This suppressive function how...

1019 Background: Whether ECE mandates ALND in patients with ≤2 positive sentinel nodes (SN) is controversial. ACOSOG Z11 excluded patients with matted nodes, but did not comment on microscopic ECE. In a prospective, consecutive series of patients, we sought to determine if ECE correlates with the number of positive axillary lymph nodes (LN) and if ECE ≤2mm clinically differs from ECE >2mm. Methods: In 8/2010 an institutional treatment algorithm based on the Z11 results was prospectively applied to consecutive patients having BCS. ALND was performed for ≥3 +SNs. The approach to ECE was not specified. Characteristics of patients with and without ECE were compared with Fisher’s exact test and the Wilcoxon rank sum test. Results: From 8/10-11/12, 2157 invasive breast cancer patients had BCS; 381 had LN metastasis, 287 met Z11 selection criteria, and ALND was avoided in 242 (84%). ECE was present in 111 (39%), of whom 23% had ≥3 +SNs (vs 2% without ECE; p2mm ECE; median of 1 additional +LN in each group. Seven or more additional +LNs were seen in 6 patients with >2mm ECE; 1 patient with ≤2mm ECE had 6 additional +LNs, the remainder had ≤3. Conclusions: The presence of ECE was associated with ≥3 +SNs and the need for ALND. Only a minority of patients with ≤2mm of ECE had ≥3 +SNs, and nodal disease at ALND in this group was limited, suggesting that ≤2mm ECE may not be an indication for ALND. [Table: see text]