Abstract P3-08-43: Comprehensive analysis of lymphopenia in large-scaled early and metastatic breast cancer database cohort
Authors: Kim Jee Hung , Kim Min Hwan , Kim Gun Min , Park Byeong-Woo , Cho Young Up , Kim Seung Il , Park Seho , Park Hyung Seok , Kim Ji Ye , Chung Hyun Cheol , Paik Soonmyung , Sohn Joohyuk 
Published: March 2020

Abstract
Background: Lymphopenia is frequently observed in advanced cancer patients even before initiation of systemic anti-cancer treatment. The aim of this study is to investigate the pre-treatment lymphopenia as a prognostic factor for breast cancer specific survival (BCSS), distant recurrence free survival (DRFS) in patients with early breast cancer (EBC) and overall survival (OS), OS2 (from diagnosis with stage IV to death) with metastatic breast cancer (MBC) in large-scaled early and metastatic breast cancer database cohort.
Methods: We reviewed demographic, clinical, pathologic, and survival data from Yonsei Breast Cancer Center Registry. In large scaled database, 5252 patients who underwent surgery with stage I-III EBC at the Yonsei Cancer Center between 2006 and 2015 were included and 1481 patients who were newly diagnosed de novo or recurrent MBC were included. The pre-treatment lymphocyte count was obtained from complete blood count (CBC) assay before the initiation of any treatment. Lymphopenia was defined as an absolute lymphocyte count (ALC) &lt; 1000/mm3. Clinicopathologic factors, such as human epidermal growth factor 2 (HER2) receptor, hormone receptor (HR) status and metastatic site, were reviewed. To evaluate the prognostic factors, Kaplan-Meier, log-rank, and Cox regression analysis were performed.
Results: Of 5211 eligible EBC patients, 2690 (51.6%) stage I and 1857 (35.6%) stage II patients was included. De novo and recurrent MBC patients were 260 (31.0%) and 576 (69.0%). The incidences of pre-treatment lymphopenia were 3.0% (154/5211) in EBC and 14.5% (121/836) in MBC: 10 (3.9%) in de novo stage IV and 117 (19.3%) in recurrent stage IV. There was no difference in pre-treatment lymphopenia incidence among histologic subtypes in EBC cohort, but it was significantly higher in triple negative breast cancer (TNBC) in MBC. EBC patients with HBsAg positive showed higher incidence of pre-treatment lymphopenia than HBV negative patients (7.3% vs. 2.9%, p=0.003). In MBC cohort, patients with early distant recurrent (less than 2 year) disease (35.8%, p&lt;0.001), HER2-negative (39.7%, p&lt;0.001), liver & brain metastasis (25.7%, p=0.028 & 30.5%, p=0.024) and without adjuvant endocrine therapy (25.8%, p&lt;0.001) were higher incidence of pre-treatment lymphopenia. In EBC cohort, pre-treatment lymphopenia would not prognostic factor in DFRS, OS and BCSS. However, in MBC cohort, pre-treatment lymphopenia group showed a significant difference in overall survival compared to normal lymphocyte count group (mOS2 19.7 vs 40.1 months, p&lt;0.0001). In de novo stage IV MBC, there is no survival difference in baseline lymphopenia as in EBC cohort. In contrast, in recurrent stage IV MBC, pre-treatment lymphopenia group showed poor survival regardless to previous exposure to neo/adjuvant chemotherapy (mOS2 in naïve chemotherapy group: lymphopenia vs no lymphopenia 19.7 vs 73.2months (p&lt;0.001); mOS2 in previous chemotherapy group: 18.2 vs 35.7months, (p&lt;0.001)). In multivariate Cox regression analysis, pre-treatment lymphopenia (HR 1.59; 95% CI 1.25-2.03; p&lt;0.001), early recurrent (&lt;2 years) (HR 1.61; 1.27-2.04; p&lt;0.001), visceral metastases (HR 1.48; 1.12-1.95; p=0.005), and TNBC subtype (HR 1.85; 1.37-2.49; p&lt;0.001) were independent prognostic factors for OS2 in recurrent stage IV MBC.
Conclusions: In this large-scaled and retrospectively analyzed a dataset, we showed highest incidence of pre-treatment lymphopenia in recurrent MBC, not affected by previous chemotherapy exposure. Pre-treatment lymphopenia was a significant poor prognostic factor in recurrent stage IV MBC, but not in EBC or de novo stage IV MBC.
Citation Format: Jee Hung Kim, Min Hwan Kim, Gun Min Kim, Byeong-Woo Park, Young Up Cho, Seung Il Kim, Seho Park, Hyung Seok Park, Ji Ye Kim, Hyun Cheol Chung, Soonmyung Paik, Joohyuk Sohn. Comprehensive analysis of lymphopenia in large-scaled early and metastatic breast cancer database cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-43.