孕期乳腺癌（PrBC）是一种罕见的疾病，以其侵袭性的临床行为而闻名。肿瘤浸润淋巴细胞（TILs）的存在已经被证明对这些患者的预后产生显著影响。尽管肿瘤的某些生物特性可能因妊娠阶段而异，但对PrBC肿瘤微环境中免疫景观的动态了解甚少。因此，在本研究中，我们的目标是全面了解孕期乳腺癌诊断的孕龄与肿瘤微环境组成之间的关系。我们选取了来自我们机构的108例PrBC病例，并根据妊娠期将其分类。对所有病例，根据国际TILs工作组的建议，对TILs进行了分析，并通过CD4、CD8和forkhead box P3（FOXP3）的免疫组化进行亚型分型。使用IHC 22C3 pharmDx试剂盒检测PD-L1，并根据组织中细胞阳性分数（CPS）进行测试，阳性值的截断值为≥10。统计分析采用Fisher检验和卡方检验，并针对多重比较进行适当的调整，采用逻辑回归模型和基于Kaplan-Meier方法的生存分析。随着妊娠期的推移，G3不分化肿瘤的比例增加（第一孕期，n = 25，56.8％；第二孕期，n = 27，69.2％；第三孕期，n = 21，87.5％；p = 0.03）。组织学亚型以及激素受体（HR）和HER2状态在不同孕期没有显示出显著变化。在HR+/HER2-亚型中，早期孕期的肿瘤中高/中度TILs的比例较高，与FOXP3表达类似（TILs：第一季度，n = 10，35.7％；第二季度，n = 2，10.5％；第三季度，n = 0； p = 0.02；FOXP3：第一季度，n = 10，40％；第二季度，n = 3，15.8％；第三季度，n = 0； p = 0.03）。我们队列的中位随访时间为81个月。在乳腺癌诊断后发生复发的患者中，第一孕期患者PD-L1阴性的比例更高，与无疾病复发的患者不同（n = 9，100％与n = 9，56.3％； p = 0.03；激素治疗和n = 9，100％与n = 7，53.9％； p = 0.02；化疗）。在生存结果方面，三个孕期之间没有统计学上显著的差异。HR+/HER2- PrBC的TME动态根据孕龄而异，这表明在后期孕龄中免疫耐受性的表达可能解释了该阶段诊断出的肿瘤的增加侵袭性。Copyright © 2023 Sajjadi, Venetis, Ivanova, Noale, Blundo, Di Loreto, Scarfone, Ferrero, Maggi, Veronesi, Galimberti, Viale, Peccatori, Fusco and Guerini-Rocco.

Breast 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.n = 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.The 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.The 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.Copyright © 2023 Sajjadi, Venetis, Ivanova, Noale, Blundo, Di Loreto, Scarfone, Ferrero, Maggi, Veronesi, Galimberti, Viale, Peccatori, Fusco and Guerini-Rocco.