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The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy.

ABSTRACT: PURPOSE:Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR+/HER2- breast tumors. EXPERIMENTAL DESIGN:HR+/HER2- breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8+ cells, CD68+ cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed. RESULTS:Ninety-six patients were analyzed from two cohorts (n = 55, Dana-Farber cohort; n = 41, MD Anderson cohort). sTIL, CD8, and PD-L1 on tumor cells were higher in tumors with basal PAM50 intrinsic subtype. Higher levels of tissue-based lymphocyte (sTIL, CD8, PD-L1) and macrophage (CD68) markers, as well as gene expression markers of lymphocyte or macrophage phenotypes (NanoString or CIBERSORT), correlated with favorable response to neoadjuvant chemotherapy, but not with improved distant metastasis-free survival in these cohorts or a large gene expression dataset (N = 302). In paired pre-/postchemotherapy samples, sTIL and CD8+ cells were significantly decreased after treatment, whereas expression analyses (NanoString) demonstrated significant increase of multiple myeloid signatures. Single gene expression implicated increased expression of immunosuppressive (M2-like) macrophage-specific genes after chemotherapy. CONCLUSIONS:The immune microenvironment of HR+/HER2- tumors differs according to tumor biology. This cohort of paired pre-/postchemotherapy samples suggests a critical role for immunosuppressive macrophage expansion in residual disease. The role of macrophages in chemoresistance should be explored, and further evaluation of macrophage-targeting therapy is warranted.

SUBMITTER: Waks AG

PROVIDER: S-EPMC6677598 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy.

Waks Adrienne G AG Stover Daniel G DG Guerriero Jennifer L JL Dillon Deborah D Barry William T WT Gjini Evisa E Hartl Christina C Lo Wesley W Savoie Jennifer J Brock Jane J Wesolowski Robert R Li Zaibo Z Damicis Adrienne A Philips Anne V AV Wu Yun Y Yang Fei F Sullivan Amy A Danaher Patrick P Brauer Heather Ann HA Osmani Wafa W Lipschitz Mikel M Hoadley Katherine A KA Goldberg Michael M Perou Charles M CM Rodig Scott S Winer Eric P EP Krop Ian E IE Mittendorf Elizabeth A EA Tolaney Sara M SM

Clinical cancer research : an official journal of the American Association for Cancer Research 20190506 15

<h4>Purpose</h4>Hormone receptor-positive/HER2-negative (HR<sup>+</sup>/HER2<sup>-</sup>) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR<sup>+</sup>/HER2<sup>-</sup> breast tumors.<h4>Experimental design</h4>HR<sup>+</su ...[more]

PMID: 31061067

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Project description:ImportanceRace disparities persist in breast cancer mortality rates. One factor associated with these disparities may be differences in symptom burden, which may reduce chemotherapy tolerance and increase early treatment discontinuation.ObjectivesTo compare symptom burden by race among women with early-stage breast cancer before starting chemotherapy and quantify symptom differences explained by baseline characteristics.Design, setting, and participantsA cross-sectional analysis of symptom burden differences by race among Black and White women with a diagnosis of stage I to III, hormone receptor-positive breast cancer who had a symptom report collected before chemotherapy initiation in a large cancer center in the southern region of the US from January 1, 2007, through December 31, 2015. Analyses were conducted from November 1, 2019, to March 31, 2021. Blinder-Oaxaca decomposition was used, adjusting for baseline sociodemographic and clinical characteristics.Main outcomes and measuresFour symptom composite scores with a mean (SD) of 50 (10) were reported before starting chemotherapy (baseline) and were derived from symptom items: general physical symptoms (11 items), treatment adverse effects (8 items), acute distress (4 items), and despair (7 items). Patients rated the severity of each symptom they experienced in the past week on a scale of 0 to 10 (where 0 indicates not a problem and 10 indicates as bad as possible).ResultsA total of 1338 women (mean [SD] age, 54.6 [11.6] years; 420 Black women [31.4%] and 918 White women [68.6%]) were included in the study. Before starting chemotherapy, Black women reported a statistically significantly higher (ie, worse) symptom composite score than White women for adverse effects (44.5 vs 43.8) but a lower acute distress score (48.5 vs 51.0). Decomposition analyses showed that Black patients' characteristics were associated with higher symptom burden across all 4 scores. However, these differences were offset by relatively greater, statistically significant, unexplained physical, distress, and despair symptom reporting by White patients.Conclusions and relevanceIn this study, before starting chemotherapy, Black patients with early-stage breast cancer reported significantly higher burden for symptoms that may be exacerbated with chemotherapy and lower distress symptoms compared with White patients. Future studies should explore how symptoms change before and after treatment and differ by racial/ethnic groups and how they are associated with treatment adherence and mortality disparities.

Dataset Information

The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy.

Publications

The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy.

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