| Autor: |
Rachel Schiff, Mothaffar F. Rimawi, Charles Kent Osborne, Carolina Gutierrez, Aleix Prat, Jorge S. Reis-Filho, Britta Weigelt, Antonio C. Wolff, Anne Pavlick, Maria Letizia Cataldo, Meghana V. Trivedi, Susan G. Hilsenbeck, Sufeng Mao, Anna Tsimelzon, Tao Wang, Paolo Nuciforo, Vidyalakshmi Sethunath, Jamunarani Veeraraghavan, Yi Zheng, Chichung Wang, Kristin Roman, Linying Liu, Cliff C. Hoyt, Chandandeep Nagi, Carmine De Angelis |
| Rok vydání: |
2023 |
| Popis: |
Purpose:Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2+ breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.Experimental Design: Hematoxylin and eosin–stained slides (n = 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER+ tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides (n = 33).Results:The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%, P = 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively; P = 0.01). In multivariable analysis, cluster 2, characterized by high CD4+, CD8+, CD20+ s-TILs, and high CD20+ intratumoral TILs, was independently associated with a higher pCR rate (P = 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20+ TILs.Conclusions:LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2+ breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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