Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis

Frontiers in Oncology

Oncology

Concetta Blundo¹  Paolo Veronesi²  Giuseppe Viale³  Elena Guerini-Rocco³  Elham Sajjadi³  Konstantinos Venetis³  Nicola Fusco³  Viviana E. Galimberti⁴  Stefano Ferrero⁵  Mariia Ivanova⁶  Fedro A. Peccatori⁷  Eugenia Di Loreto⁸  Giovanna Scarfone⁸  Stefania Maggi⁹  Marianna Noale⁹ 

[1] Breast Surgery Unit, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Milan, Italy;Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy;Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy;Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy;Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy;Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy;Division of Pathology, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Milan, Italy;Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy;Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy;Fertility and Procreation Unit, Division of Gynecologic Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy;Gynecology Unit, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Milan, Italy;Neuroscience Institute Aging Branch, National Research Council (CNR), Padua, Italy;

关键词: breast cancer during pregnancy;    pregnancy-associated breast cancer;    PD-L1;    Foxp3;    tumor microenvironment;    breast cancer;    tumor-infiltrating lymphocytes (TILs);   

DOI  :  10.3389/fonc.2023.1116569

 received in 2022-12-05, accepted in 2023-07-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundBreast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME.Methodsn = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher’s and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan–Meier method.ResultsThe proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2– subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome.ConclusionThe TME dynamics of HR+/HER2− PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.

【 授权许可】

Unknown   
Copyright © 2023 Sajjadi, Venetis, Ivanova, Noale, Blundo, Di Loreto, Scarfone, Ferrero, Maggi, Veronesi, Galimberti, Viale, Peccatori, Fusco and Guerini-Rocco