曲妥珠单抗对乳腺癌巨噬细胞相关信号因子及预后的影响

doi:10.3969/j.issn.1006-6233.2024.11.08

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (1372 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To investigate the impact of trastuzumab on macrophage-related signaling factors and prognosis in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.Methods: A total of 155 patients with primary, non-metastatic HER2⁺ breast cancer who underwent surgery between January 2013 and December 2020 were enrolled in this study. Immunohistochemistry was used to analyze the expression levels of CD8⁺, CD4⁺, FOXP3⁺ tumor-infiltrating lymphocytes (TILs) and CD68⁺, CD163⁺ tumor-associated macrophages (TAMs) in tumor tissues. Spearman correlation analysis was used to assess the correlation between TILs and TAMs. Univariate and multivariate Cox regression analyses were performed to evaluate prognostic factors in patients who received adjuvant trastuzumab therapy.Results: Thirty-two patients (20.6%) died during the follow-up period. The median follow-up time for all patients was 53.57 months (range, 33.30~72.37). FOXP3⁺ TIL counts were positively correlated with CD4⁺ and CD8⁺ TIL counts (P<0.001). CD4⁺, CD8⁺, and FOXP3⁺ TIL counts were positively correlated with CD163⁺ and CD68⁺ TAM counts (P<0.001). Cox regression analysis showed that lymphovascular invasion (OR=2.631, 95% CI=1.218-5.685), CD68⁺ TAM (OR=1.002, 95% CI=1.001-1.003), CD8⁺ TIL (OR=1.002, 95% CI=1.001-1.004), and Ki-67 proliferation index (OR=0.998, 95% CI=0.997-1.000) were independent prognostic factors for patients receiving adjuvant trastuzumab therapy (P<0.05). ROC analysis showed that when the cutoff value for CD68⁺ TAM was 235.33, the AUC for predicting patient death was 0.933 (95% CI=0.896~0.970), with a sensitivity of 93.8% and a specificity of 83.7%. When the cutoff value for CD8⁺ TIL was 53.67, the AUC for predicting patient death was 0.645 (95% CI=0.536-0.754), with a sensitivity of 56.3% and a specificity of 65.0%.Conclusion: High counts of CD68⁺ TAM and CD8⁺ TIL were associated with poor prognosis in HER2⁺ breast cancer patients receiving trastuzumab therapy, and CD68⁺ TAM counts had a higher predictive value for adverse prognosis.

Key words： Trastuzumab Breast cancer Human epidermal growth factor receptor 2 Tumor-infiltrating lymphocytes Tumor-associated macrophages

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	LIU Fangli
	ZHOU Xiaoyan

Cite this article:

LIU Fangli,ZHOU Xiaoyan. Impact of Trastuzumab on Macrophage-Related Signaling Factors and Prognosis in Breast Cancer[J]. HeBei Med, 2024, 30(11): 1803-1808.

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.11.08 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I11/1803

[1] Von Arx C,De Placido P,Caltavituro A,et al.The evolving therapeutic landscape of trastuzumab-drug conjugates: guture perspectives beyond HER2-positive breast cancer[J].Cancer Treat Rev,2023(113): 102500.
[2] Hurviz S A,Hegg R,Chung W P,et al.Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03,a randomised,open-label,phase 3 trial[J].Lancet,2023,401(10371): 105-117.
[3] Liefaard M C,Van Der Voort A,Van Seijen M,et al.Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade[J].NPJ Breast Cancer,2024,10(1): 29.
[4] He J,Fu F,Wang W,et al.Prognostic value of tumour-infiltrating lymphocytes based on the evaluation of frequency in patients with oestrogen receptor~positive breast cancer[J].Eur Cancer,2021(154): 217-226.
[5] Gao Z,Li C,Liu M,et al.Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis[J].BMC cancer,2020,20(1): 1150.
[6] Fernandez-maritinez A,Pascual T,Singh B,et al.Prognostic and predictive value of immune-related gene expression signatures vs tumor-infiltrating lymphocytes in early-stage ERBB2/HER2-positive breast cancer: a correlative analysis of the CALGB 40601 and PAMELA trials[J].JAMA Oncol,2023,9(4): 490-499.
[7] Jaaskelainen M M,Tumelius R,Hamalainen K,et al.High numbers of CD163⁺ tumor-associated macrophages predict poor prognosis in HER2⁺ breast cancer[J].Cancers,2024,16(3): 634.
[8] Hendry S,Salgado R,Gevaert T,et al.Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TIL in melanoma,gastrointestinal tract carcinomas,non~small cell lung carcinoma and mesothelioma,endometrial and ovarian carcinomas,squamous cell carcinoma of the head and neck,genitourinary carcinomas,and primary brain tumors[J].Adv Anat Pathol,2017,24(6): 311-335.
[9] Wynn C S,Tang S C.Anti-HER2 therapy in metastatic breast cancer: many choices and future directions[J].Cancer Metastasis Rev,2022,41(1): 193-209.
[10] Chen Y,Klingen T A,Aas H,et al.Tumor‐associated lymphocytes and macrophages are related to stromal elastosis and vascular invasion in breast cancer[J].J Pathol Clin Res,2021,7(5): 517-527.
[11] Nelson M A,Ngamcherdtrakul W,Luoh S W,et al.Prognostic and therapeutic role of tumor-infiltrating lymphocyte subtypes in breast cancer[J].Cancer Metastasis Rev,2021,40(2): 519-536.
[12] Anderson N R,Minutolo N G,Gill S,et al.Macrophage-based approaches for cancer immunotherapy[J].Cancer Res,2021,81(5): 1201-1208.
[13] Lotfinejad P,Asghari Jafarabadi M,Abdoli Shadbad M,et al.Prognostic role and clinical significance of tumor-infiltrating lymphocyte (TIL) and programmed death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC): a systematic review and meta-analysis study[J].Diagnostics,2020,10(9): 704.
[14] Nagano M,Saito K,Kozuka Y,et al.CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression[J].Oncol Lett,2021,21(1): 36.
[15] Baez-navarro X,Van Den Ende N S,Nguyen A H,et al.HER2-low and tumor infiltrating lymphocytes in triple-negative breast cancer: are they connected[J].Breast Cancer Res,2024,26(1): 41.
[16] Chen Y,Klingen T A,Aas H,et al.Tumor-associated lymphocytes and macrophages are related to stromal elastosis and vascular invasion in breast cancer[J].Pathol Clin Res,2021,7(5): 517-527.
[17] Jaaskelainen M M,Tiainen S,Siiskonen H,et al.The prognostic and predictive role of tumor-infiltrating lymphocytes (FoxP3⁺ and CD8⁺) and tumor-associated macrophages in early HER2⁺ breast cancer[J].Breast Cancer Res Treat,2023,201(2): 183-192.
[18] Fernadez-martinez A,Pascual T,Singh B,et al.Prognostic and predictive value of immune-related gene expression signatures vs tumor-infiltrating lymphocytes in early-stage ERBB2/HER2-positive breast cancer: a correlative analysis of the CALGB 40601 and PAMELA trials[J].JAMA Oncol,2023,9(4): 490-499.