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Supplemental Figures and Tables from Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer

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posted on 2023-03-31, 19:43 authored by Anosheh Afghahi, Natasha Purington, Summer S. Han, Manisha Desai, Emma Pierson, Maya B. Mathur, Tina Seto, Caroline A. Thompson, Joseph Rigdon, Melinda L. Telli, Sunil S. Badve, Christina N. Curtis, Robert B. West, Kathleen Horst, Scarlett L. Gomez, James M. Ford, George W. Sledge, Allison W. Kurian

Supplemental Figure 1. Patient inclusion and exclusion criteria. TNBC: triple negative breast cancer; ALC: absolute lymphocyte count; nSES: neighborhood socioeconomic status. Supplemental Figure 2a and 2b. Association between minimum lymphocyte count (as percentage of total white blood cell count and absolute value) and stromal tumor infiltrating lymphocytes (sTILs), N=77. Figure 2a. sTILs were correlated with minimum % lymphocyte (p=0.02). Figure 2b. sTILs did not have a significant correlation with minimum absolute (abs) lymphocytes (p=0.36) Supplemental Figure 3. Comparison between Absolute Lymphocyte Count (ALC) and percent peripheral lymphocytes Supplemental Figure 4. Distribution of Absolute Lymphocyte Count (ALC) measures at baseline, defined as ALC value measured within the first three months of breast cancer diagnosis. Supplemental Figure 5. Distribution of minimum Absolute Lymphocyte Count (ALC) values at any time point Supplemental Figure 6. Distribution of overall minimum Absolute Lymphocyte Count (ALC) over time Supplemental Table 1. Multivariable analysis of predictors of lymphopenia (absolute lymphocyte count [ALC] <1K/�L; n=747); statistically significant variables are in bold font. Supplemental Table 2. Multivariable analysis of the association between minimum absolute lymphocyte count (ALC) and breast cancer-specific mortality using complete case analysis (n=747) †Supplemental Table 3. Multivariable analysis of the association between minimum absolute lymphocyte count (ALC) and breast cancer-specific mortality using multiple imputation methods Supplemental Table 4. Multivariable analysis of the association between minimum ALC and OM with RT temporal consideration (n=747) Supplemental Table 5. Multivariable analysis of the association between minimum ALC and BCM with RT temporal consideration (n=747) Supplemental Table 6. Multivariable analysis of the association between minimum ALC and OM with neutropenia temporal consideration (n=747) Supplemental Table 7. Multivariable analysis of the association between minimum ALC and BCM with neutropenia temporal consideration (n=747) Supplemental Table 8. Multivariable analysis of the association between minimum percent lymphocyte count and overall mortality using complete case analysis (n=532). Supplemental Table 9. Multivariable analysis of the association between minimum percent lymphocyte count and breast-cancer specific mortality using complete case analysis (n=532)

Funding

Susan and Richard Levy Gift Fund

Suzanne Pride Bryan Fund for Breast Cancer Research

Breast Cancer Research Foundation

Susan G. Komen for the Cure Foundation

Jan Weimer Junior Faculty Chair in Breast Oncology

Regents of the University of California's California Breast Cancer Research Program

Stanford University Developmental Research Fund

BRCA Foundation

NCI's Surveillance, Epidemiology, and End Results Program

NIH CTSA

California Department of Health Services

Cancer Prevention Institute of California

Centers for Disease Control and Prevention's National Program of Cancer Registries

History

ARTICLE ABSTRACT

Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer–specific mortality (BCM) and overall mortality (OM) in TNBC.Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts.Results: A total of 1,463 stage I–III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16–0.35] and BCM (HR = 0.19; CI, 0.11–0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy.Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment. Clin Cancer Res; 24(12); 2851–8. ©2018 AACR.