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雄激素受体和肿瘤浸润淋巴细胞与三阴性乳腺癌骨转移的相关性

Association of androgen receptor and tumour-infiltrating lymphocytes with bone recurrence in triple-negative breast cancer.

作者信息

Ilenič Petra, Herman Ajda, Langerholc Erik, Gazić Barbara, Šeruga Boštjan

机构信息

University Medical Centre Ljubljana, Zaloška cesta 2, Ljubljana, Slovenia.

Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.

出版信息

J Bone Oncol. 2023 Dec 23;44:100518. doi: 10.1016/j.jbo.2023.100518. eCollection 2024 Feb.

Abstract

BACKGROUND

As compared to endocrine responsive breast cancer bone is less frequent site of distant recurrence in triple-negative breast cancer (TNBC). A biomarker which predicts bone recurrence would allow a more personalized treatment approach with adjuvant bisphosphonates in TNBC. Here we hypothesised that tumour expression of androgen receptor (AR) is associated with bone recurrence in TNBC.

MATERIALS AND METHODS

Patients with operable TNBC who were treated at the Institute of Oncology Ljubljana between 2005 and 2015 and developed distant recurrence were included into our study. Nuclear expression of AR in the tissue of primary tumours was determined immunohistochemically by using the Androgen Receptor (SP107) Rabbit Monoclonal Antibody. We applied a logistic regression model to test the association between expression of AR and development of bone metastases. The model was adjusted for selected known prognostic factors and possible confounders in TNBC, including the level of the stromal tumour-infiltrating lymphocytes (sTILs).

RESULTS

At recurrence 45 (45 %) out of 100 patients presented with bone metastases. Additionally, seven (7 %) developed bone metastases metachronously. AR was expressed in primary tumours of 35 (35 %) women and 19 (54.3 %) developed bone recurrence. In 25 (25 %) patients sTILs were absent. Neither the proportion of AR positive cancer cells (OR = 1.00; 95 % CI 0.96-1.03; p = 1.00) nor the intensity of AR positive reaction (OR = 0.71; 95 % CI 0.02-21.4; p = 1.00) were significantly associated with bone recurrence. However, women with at least mild level of the sTILs were at significantly lower risk for bone recurrence as compared to those without any sTILs (OR = 0.01; 95 % CI < 0.01-0.08; p = 0.01).

CONCLUSIONS

Expression of AR is not significantly associated with the development of bone metastases in TNBC. However, patients with absent sTILs in their primary tumours are highly susceptible for recurrence in the bone and might particularly benefit from adjuvant bisphosphonates.

摘要

背景

与激素受体阳性乳腺癌相比,骨转移在三阴性乳腺癌(TNBC)中作为远处复发部位的情况较少见。一种能够预测骨转移复发的生物标志物将有助于为TNBC患者提供更具个性化的辅助双膦酸盐治疗方案。在此,我们假设雄激素受体(AR)的肿瘤表达与TNBC的骨转移复发相关。

材料与方法

纳入2005年至2015年间在卢布尔雅那肿瘤研究所接受治疗且发生远处转移的可手术TNBC患者。采用雄激素受体(SP107)兔单克隆抗体,通过免疫组织化学方法检测原发肿瘤组织中AR的核表达。我们应用逻辑回归模型来检验AR表达与骨转移发生之间的关联。该模型针对TNBC中选定的已知预后因素和可能的混杂因素进行了校正,包括基质肿瘤浸润淋巴细胞(sTILs)水平。

结果

在复发时,100例患者中有45例(45%)出现骨转移。此外,7例(7%)患者出现异时性骨转移。35例(35%)女性的原发肿瘤中表达AR,其中19例(54.3%)发生骨转移复发。25例(25%)患者不存在sTILs。AR阳性癌细胞比例(OR = 1.00;95%CI 0.96 - 1.03;p = 1.00)和AR阳性反应强度(OR = 0.71;95%CI 0.02 - 21.4;p = 1.00)均与骨转移复发无显著相关性。然而,与无任何sTILs的患者相比,sTILs至少为轻度水平的女性发生骨转移复发的风险显著降低(OR = 0.01;95%CI < 0.01 - 0.08;p = 0.01)。

结论

AR表达与TNBC骨转移的发生无显著相关性。然而,原发肿瘤中不存在sTILs的患者发生骨转移复发的风险很高,可能特别受益于辅助双膦酸盐治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fdc/10874935/d6ef4afb8a37/ga1.jpg

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