TY - JOUR
T1 - Metastatic triple-negative breast cancers at first relapse have fewer tumor-infiltrating lymphocytes than their matched primary breast tumors
T2 - A pilot study
AU - Cimino-Mathews, Ashley
AU - Ye, Xiaobu
AU - Meeker, Alan
AU - Argani, Pedram
AU - Emens, Leisha A.
N1 - Funding Information:
This work was supported by the Department of Defense (Clinical Translational Research Award W81XWH-07-1-0485), the American Cancer Society (RSG CCE 112685), the Specialized Programs in Research Excellence (SPORE) in Breast Cancer (P50CA88843), Genentech Incorporated, the Gateway Foundation, the Avon Foundation, and the V Foundation. The authors would also like to acknowledge Jessica Hicks for technical assistance with staining of the TMAs.
Funding Information:
Dr Emens receives research funding from Genentech, Incorporated , and has received honoraria for participating on regional advisory panels for Genentech, Incorporated, Roche Incorporated, and Bristol Myers Squibb. Under a licensing agreement between Aduro, Incorporated, and the Johns Hopkins University, the University is entitled to milestone payments and royalty on sales of the granulocyte macrophage colony-stimulating factor (GM-CSF)–secreting breast cancer vaccine. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. All other authors report no conflict of interest to disclose.
PY - 2013/10
Y1 - 2013/10
N2 - Summary Tumor-infiltrating lymphocytes (TILs) convey clinically relevant information for primary breast cancers (PBCs). However, limited data characterizing the immunobiology of metastatic breast cancers (MBCs) are available. Here, we examine TILs in surgically resected MBCs relative to their matched PBCs. Tissue microarrays of PBCs and MBCs were labeled for CD3 (total T cells), CD4 (helper T cells), CD8 (cytotoxic T cells), FoxP3 (regulatory T cells), and CD20 (B cells) to characterize TILs. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER-2) classified the tumors as luminal (ER+/PR+/HER-2 -), triple negative (ER-/PR-/HER-2 -), or HER-2+ (ER-/PR-/HER-2 +). These analyses reveal 5 novel findings. First, MBCs overall contained fewer TILs (mean, 35.1 CD3+ TILs/high-power field [hpf]) than their matched PBCs (mean, 23.6 CD3+ TILS/hpf), with fewer CD20+ cells than CD3+ cells in PBC and MBC (P =.0247). Second, the number of CD3+, CD8+, CD4+, and FoxP3 TILs was decreased in triple-negative MBCs relative to matched PBCs, whereas only CD8+ TILs were decreased in luminal MBCs relative to matched PBCs. Third, triple-negative MBCs contain fewer TILS (mean, 16 CD3 + TILs/hpf) than luminal MBCs (mean, 21.7 CD3+ TILs/hpf). Fourth, brain metastases contained fewer TILs relative to MBC from other sites. Finally, in this series, a CD8+/FoxP3+ T-cell ratio of 3 or greater in PBCs was associated with improved overall survival from diagnosis, whereas a CD8+/FoxP3+ T-cell ratio less than 3 in MBCs at first relapse was associated with improved overall survival. These findings suggest that evaluating the immunologic microenvironment of both PBCs and MBCs may yield important clinical information to guide breast cancer prognosis and therapy.
AB - Summary Tumor-infiltrating lymphocytes (TILs) convey clinically relevant information for primary breast cancers (PBCs). However, limited data characterizing the immunobiology of metastatic breast cancers (MBCs) are available. Here, we examine TILs in surgically resected MBCs relative to their matched PBCs. Tissue microarrays of PBCs and MBCs were labeled for CD3 (total T cells), CD4 (helper T cells), CD8 (cytotoxic T cells), FoxP3 (regulatory T cells), and CD20 (B cells) to characterize TILs. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER-2) classified the tumors as luminal (ER+/PR+/HER-2 -), triple negative (ER-/PR-/HER-2 -), or HER-2+ (ER-/PR-/HER-2 +). These analyses reveal 5 novel findings. First, MBCs overall contained fewer TILs (mean, 35.1 CD3+ TILs/high-power field [hpf]) than their matched PBCs (mean, 23.6 CD3+ TILS/hpf), with fewer CD20+ cells than CD3+ cells in PBC and MBC (P =.0247). Second, the number of CD3+, CD8+, CD4+, and FoxP3 TILs was decreased in triple-negative MBCs relative to matched PBCs, whereas only CD8+ TILs were decreased in luminal MBCs relative to matched PBCs. Third, triple-negative MBCs contain fewer TILS (mean, 16 CD3 + TILs/hpf) than luminal MBCs (mean, 21.7 CD3+ TILs/hpf). Fourth, brain metastases contained fewer TILs relative to MBC from other sites. Finally, in this series, a CD8+/FoxP3+ T-cell ratio of 3 or greater in PBCs was associated with improved overall survival from diagnosis, whereas a CD8+/FoxP3+ T-cell ratio less than 3 in MBCs at first relapse was associated with improved overall survival. These findings suggest that evaluating the immunologic microenvironment of both PBCs and MBCs may yield important clinical information to guide breast cancer prognosis and therapy.
KW - Breast cancer
KW - FoxP3
KW - Regulatory T cells (Treg)
KW - Tumor-infiltrating lymphocytes (TILs)
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U2 - 10.1016/j.humpath.2013.03.010
DO - 10.1016/j.humpath.2013.03.010
M3 - Article
C2 - 23701942
AN - SCOPUS:84884413571
SN - 0046-8177
VL - 44
SP - 2055
EP - 2063
JO - Human pathology
JF - Human pathology
IS - 10
ER -