Abstract P1-20-01: Immune microenvironment change of breast cancer and bone metastasis
Authors: Chao Xue , Zhang Ying , Lu Jiabin , Sun Peng , He Jiehua 
Published: March 2022

Background: Bone is one of the most frequent sites for breast cancer metastasis. Breast cancer bone metastasis leads to skeletal morbidity including pain, fractures, spinal compression, and impact quality of life. Immunotherapy is a promising therapy for advanced cancer patients. Thus, a better understanding of the immune microenvironment for breast cancer and its bone metastasis sites may prompt new therapy strategies. This study aimed to investigate immune parameters change between breast cancer and its bone metastasis site. Methods: 63 patients with breast cancer bone metastasis including 31 paired primary sites with bone metastasis were included in our study. The percentage of stroma and stromal tumor infiltrated lymphocytes (TILs) was evaluated through hematoxylin and eosin stained tumor slides. The quantification of stromal TILs (CD4, CD8) and macrophages (CD68, HLA-DR), programmed cell death protein 1(PD-1), and programmed cell death protein ligand 1(PD-L1, SP142) were evaluated through immunohistochemical staining. Statistical analysis was performed with paired t-test, Wilcoxon test, spearman correlation test, univariate and multivariate cox regression. Results: Median survival after breast cancer bone metastasis was pathologically diagnosed was 20.5 months (3-95 months). None of the immune parameters was found correlated with survival after bone metastasis. Compared to the primary site, bone metastases exhibited more stroma (mean: 58.5% vs 28.87%, p&lt;0.001) and less TILs (mean: 8.45% vs 14.03%, p=0.042). The quantification of CD4 (23.95/mm2 vs 51.69/mm2, p=0.026) and CD8 (18.15/mm2 vs 58.95/mm2, p=0.004) positive TILs also followed this tendency. The number of macrophages (CD68 and HLA-DR) showed no significant difference between primary sites and bone metastases. PD-1 expression was present in 87.1% of the primary sites and 74.19% of the bone metastasis. PD-L1 expression was present in 25.81% of the primary sites and 7.94% of the bone metastasis. Conclusions: Our findings suggest that compared with the primary site, bone metastasis obtain a less active immune microenvironment. Positive expression of PD1 and PD-L1 in bone metastasis indicates potential therapeutic effects of immune checkpoint inhibitors in some cases.

Table 1.Patient CharacteristicsVariableN%Bone metastasis leisions63Primary tumor and matched bone metastasis3149.21Primary tumor histologyDuctal , non-special type5180.95Ductal, micropapillary11.59Ductal, mucinous23.17Ductal and lobular23.17Uncertain711.11Primary tumor grade111.5921523.8134063.49Uncertain711.11Primary tumor phenotypesLuminal A1117.46Luminal B2946.03HER2 amplification1523.81Triple negative46.35Uncertain46.35Primary tumor size≤2 cm1117.462-5 cm2438.10&gt;5cm23.17Uncertain2641.27Nodes statusNegative1015.871-3 nodes2031.754-9 nodes46.35&gt;101320.63Uncertain1625.40SurgeryMastectomy4469.84Breast conserving surgery57.94None57.94Uncertain914.29Chemotherapyadjuvant5485.71neoadjuvant11.59None812.70Radiotherapyadjuvant2641.27None3758.73Trastuzumab/pertuzumab application in Her-2 positive patients7/15Endocrine therapyYes4063.49No2336.51Bone metastasis at first diagnosis57.94Bone metastasis sitesIlium57.94Sternum711.11Rib11.59Vertebra4368.25Femur34.76Humerus11.59Skull11.59Treatment after bone metastasisRadiotherapy812.70Chemotherapy2742.86Endocrine therapy4266.67Trastuzumab/pertuzumab46.35Alive at last follow-up4368.25

Table 2.Assessment of tumor microenviroment of breast cancer bone metastasisVariable MedianIQRStroma (%)7040-80Stromal TILs(%)55-10Stromal CD4+ TILs (/mm2)12.51-27.5Stromal CD8+ TILs (/mm2)51-35CD4/CD8 ratio10.53-5.18Stromal HLA-DR+ macrophages (/mm2)8560-120Stromal CD68+ macrophages (/mm2)37.512.5-57.5HLA-DR/CD68 ratio2.271.44-5PD-1 expression43/6368.25(%)PD-L1 expression5/637.94(%)Osteoclasts(/mm2)0.330-3

Citation Format: Xue Chao, Ying Zhang, Jiabin Lu, Peng Sun, Jiehua He. Immune microenvironment change of breast cancer and bone metastasis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-20-01.