PO.TB10.05 · 肿瘤生物学
吸烟与乳腺癌中肿瘤浸润淋巴细胞密度降低相关
Smoking is associated with reduced tumor-infiltrating lymphocyte density in breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
目的：既往研究检验乳腺癌（BC）中吸烟与基质肿瘤浸润淋巴细胞（TIL）之间关系时报告了相互矛盾的发现，从无显著关联到提示吸烟可能改变免疫肿瘤微环境（TME）并可能增加TIL密度的证据不等。本研究旨在阐明吸烟是否与BC中的TIL密度相关。
方法：在前瞻性的南瑞典黑色素瘤（MISS）研究中，对1992年3月1日至2013年10月31日期间诊断为原发浸润性BC的1,276名女性提供了组织微阵列（TMA）。由一名乳腺病理学家成功注释了1,173例（91.9%）肿瘤中TIL的存在，并根据染色TIL的百分比将其分为三类：低（<10%）、中（10-49%）或高（≥50%）。使用Pearson卡方检验和多变量线性回归评估TIL类别与1990-1993年研究纳入时的曾吸烟情况、BC诊断年龄、肿瘤大小、淋巴结状态、组织学分级和三阴性亚型之间的关联。双尾p值<0.05被视为具有统计学意义。
结果：BC诊断时的中位年龄为61岁（四分位距53-69岁）。在评分了TIL的TMA中，839例（71.5%）被分类为低，259例（22.1%）为中，75例（6.4%）为高。吸烟与较低的TIL密度显著相关（p=0.033，校正后趋势P=0.013）。BC诊断年龄与较低的TIL密度呈临界关联（校正后趋势P=0.060）。较高的TIL密度与更大的肿瘤（p<0.001，校正后趋势P=0.023）、更高的组织学分级（p<0.001，校正后趋势P<0.001）和三阴性亚型（p<0.001，校正后趋势P<0.001）相关。淋巴结阳性率在中等组中最高，无线性关联（p=0.006，校正后趋势P=0.57）。
结论：在这个大型前瞻性队列中，吸烟独立地与乳腺癌中显著较低的TIL密度相关，而TIL与其他临床病理因素之间的关联符合预期。这些发现提示吸烟可能对免疫TME产生负面影响，并为吸烟可能改变乳腺癌治疗应答的机制提供了新的见解。有必要开展进一步研究以探讨吸烟对乳腺癌TIL的临床影响。
查看英文原文 English abstract
Purpose: Previous studies examining the relationship between smoking and stromal tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) have reported conflicting findings, ranging from no significant association to evidence suggesting that smoking may modify the immune tumor microenvironment (TME) and potentially increase TIL density. This study aimed to clarify whether smoking is associated with TIL density in BC.
Methods: Within the prospective Melanoma in Southern Sweden (MISS) study, tissue micro arrays (TMAs) were available for 1,276 women diagnosed with a primary invasive BC between March 1, 1992, and October 31, 2013. The presence of TIL was successfully annotated in 1,173 (91.9%) tumors by a breast pathologist and classified into three categories based on the percentage of stained TILS as low (<10%), intermediate (10-49%), or high (≥50%). Associations between TIL categories and ever smoking at study inclusion between 1990-1993, age at BC diagnosis, tumor size, nodal status, histological grade, and triple-negative subtype were assessed using Pearson's Chi² test and multivariable linear regression. Two-tailed p -values <0.05 were considered statistically significant.
Results: Median age at BC diagnosis was 61 years (interquartile range 53-69 years). Of the TMAs with TILs scored, 839 (71.5%) were classified as low, 259 (22.1%) as intermediate, and 75 (6.4%) as high. Smoking was significantly associated with lower TIL density ( p = 0.033, adjusted P trend = 0.013). Age at BC diagnosis showed a borderline association with lower TIL density (adjusted P trend = 0.060). Higher TIL density was associated with larger tumor size ( p < 0.001, adjusted P trend = 0.023), higher histological grade ( p < 0.001, adjusted P trend < 0.001), and triple-negative subtype ( p < 0.001, adjusted P trend < 0.001). Nodal positivity was highest in the intermediate group, with no linear association ( p = 0.006, adjusted P trend = 0.57).
Conclusions: In this large prospective cohort, smoking was independently associated with significantly lower TIL density in breast cancer, while associations between TILs and other clinicopathological factors were as expected. These findings suggest that smoking may negatively influence immune TME and shed new light on a mechanism through which smoking could modify response to breast cancer treatments. Further studies are warranted to explore the clinical impact of smoking on TILs in breast cancer.
利益披露 Disclosure
A. M. Augustinsson, None..
K. Isaksson, None.
A. Kovács,
Roche Received honoraria.
Astra Zeneca Received honoraria.
H. Jernström, None.