4.7 Article

Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy

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CLINICAL CANCER RESEARCH
卷 26, 期 3, 页码 738-745

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AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-1402

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资金

  1. NIH SPORE Grants [P50 CA058183, CA186784]
  2. Cancer Center Grants [P30 CA125123, P30 CA008748]
  3. Breast Cancer Research Foundation [BCRF-17-143]
  4. Cancer Prevention & Research Institute of Texas [CPRIT RP 140102]
  5. Conquer Cancer Foundation-Gianni Bonadonna Breast Cancer Research Fellowship
  6. Instituto de Salud Carlos III [PI16/00904]
  7. Department of Defense [W81XWH-17-1-0579, W81XWH-17-1-0580]
  8. Translational Breast Cancer Research Consortium (TBCRC)
  9. TBCRC
  10. AVON Foundation
  11. Susan G. Komen

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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 paraffinembedded 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 wasmarginally 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.

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