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

被引：52

作者：

De Angelis, Carmine ^{[1
,2
,3
,4
]}

Nagi, Chandandeep ^{[1
,2
]}

Hoyt, Cliff C. ^{[5
]}

Liu, Linying ^{[5
]}

Roman, Kristin ^{[5
]}

Wang, Chichung ^{[5
]}

Zheng, Yi ^{[5
]}

Veeraraghavan, Jamunarani ^{[1
,2
,3
]}

Sethunath, Vidyalakshmi ^{[1
,2
,3
]}

Nuciforo, Paolo ^{[6
]}

Wang, Tao ^{[1
,2
]}

Tsimelzon, Anna ^{[1
,2
,3
]}

Mao, Sufeng ^{[1
,2
,3
]}

Hilsenbeck, Susan G. ^{[1
,2
,3
]}

Trivedi, Meghana V. ^{[1
,2
,3
,7
]}

Cataldo, Maria Letizia ^{[1
,2
,3
,4
]}

Pavlick, Anne ^{[1
,2
]}

Wolff, Antonio C. ^{[8
]}

Weigelt, Britta ^{[9
]}

Reis-Filho, Jorge S. ^{[9
]}

Prat, Aleix ^{[10
,11
]}

Gutierrez, Carolina ^{[1
,2
,3
]}

Osborne, Charles Kent ^{[1
,2
,3
]}

Rimawi, Mothaffar F. ^{[1
,2
,3
]}

Schiff, Rachel ^{[1
,2
,3
]}

机构：

[1] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[4] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy

[5] Akoya Biosci, Hopkinton, MA USA

[6] VHIO, Breast Canc Grp, Barcelona, Spain

[7] Univ Houston, Coll Pharm, Dept Pharm Practice & Translat Res, Houston, TX 77030 USA

[8] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA

[9] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[10] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain

[11] August Pi & Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain

来源：

CLINICAL CANCER RESEARCH | 2020年 / 26卷 / 03期

关键词：

PATHOLOGICAL COMPLETE RESPONSE; GUIDELINE RECOMMENDATIONS; AMERICAN-SOCIETY; PLUS TRASTUZUMAB; PROGNOSTIC VALUE; LYMPHOCYTES; LAPATINIB; MULTICENTER; MODULATION; PERTUZUMAB;

D O I：

10.1158/1078-0432.CCR-19-1402

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：738 / 745

页数：8

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