Abstract 4852: High brain relapse rates in stage III triple negative inflammatory breast cancer are independent of systemic therapy
Authors: Nasrazadani Azadeh , Kai Megumi , Layman Rachel , Valero Vicente , Saleem Sadia , Debeb Bisrat G. , Lucci Anthony , Sun Susie X. , Bopparaju Swetha , Murphy Hope E. , Alexander Angela , Marx Angela N. , Stauder Michael C. , Lim Bora , Woodward Wendy A. 
Published: March 2024

Abstract
Background - Inflammatory breast cancer (IBC) is an aggressive subtype of invasive breast carcinoma that confers a comparatively poorer prognosis owing to consistently observed inferior responses to systemic therapies as compared to non-IBC cases. Triple negative (TN) breast cancer which is characterized by lack of estrogen receptor (ER) and progesterone receptor (PR) expression, as well as by lack of HER2 amplification portends particularly poor outcomes including high rates of brain failure. Here we reviewed our prospective IBC registry data for contemporary TNIBC patients to assess current outcomes and brain failure risk in the context of standard neoadjuvant immunotherapy.
Methods - Given the change to the inclusion of pembrolizumab in addition to chemotherapy in the neoadjuvant setting in 2020, we reviewed records from 2016-2023 for Stage III TNIBC patients who presented to MD Anderson Cancer Center (MDACC) prior to receiving other therapy. TNIBC was defined as ER &lt;1%, PR &lt;1%, HER2 IHC 0/1+ or ISH-. N = 38. We examined PCR and brain mets as first failure by regimen (KN522, ACT, AC/TC) and compared using descriptive statistics. Log rank statistic was used to compare overall survival (OS) by PCR. Patients with stage III TNIBC who started the KN522 regimen achieved a pCR rate of 35% (N= 20) and pCR was less frequent in postmenopausal KN522 patients (1/7 PCRs. P = 0.016). Among this cohort, 20% of patients experienced relapse in the CNS as a site of first failure including two patients who achieved a PCR, and 25% had any brain failure at a median follow up post-surgery of 8M. Among 9 patients treated with AC/T 22% achieved pCR with 22% brain metastasis relapse rate as site of first failure and 33% overall was observed at a median follow up of 14M post-surgery. In 9 patients receiving AC/TC, the PCR was 44% and any brain relapse rate was 22%, 1/2 was a site of first failure, median follow up 38M. Despite similarities in brain relapse rates, achieving pCR nonetheless correlated with improved overall survival, P &lt; 0.05. For comparison, among 11 stage IV TNIBC patients treated with neoadjuvant systemic therapy pre-KN522, median follow up 22M from initial diagnosis, 6/11 patients developed brain involvement, 5/6 as a site of first failure. Given small numbers it is difficult to compare PCR by regimen, however we note the PCR in KN522 is lower than expected, and the rate of brain metastases particularly as a site of first failure is consistently high across regimens regardless of PCR. It is critical to consider brain penetrance of neoadjuvant systemic therapies, brain staging and even prophylaxis of brain metastasis in patients with non-metastatic and metastatic TNIBC. Current efforts are ongoing to determine molecular signatures which may aid in prognostication and potentially study design to incorporate prophylactic therapies with the overarching goal of improving outcomes in patients with triple negative IBC.
Citation Format: Azadeh Nasrazadani, Megumi Kai, Rachel Layman, Vicente Valero, Sadia Saleem, Bisrat G. Debeb, Anthony Lucci, Susie X. Sun, Swetha Bopparaju, Hope E. Murphy, Angela Alexander, Angela N. Marx, Michael C. Stauder, Bora Lim, Wendy A. Woodward. High brain relapse rates in stage III triple negative inflammatory breast cancer are independent of systemic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4852.