TY - JOUR
T1 - Integrative prognostic analysis of tumor–infiltrating lymphocytes, CD8, CD20, programmed cell death-ligand 1, and tertiary lymphoid structures in patients with early-stage triple-negative breast cancer who did not receive adjuvant chemotherapy
AU - Yazaki, Shu
AU - Shimoi, Tatsunori
AU - Yoshida, Masayuki
AU - Sumiyoshi-Okuma, Hitomi
AU - Arakaki, Motoko
AU - Saito, Ayumi
AU - Kita, Shosuke
AU - Yamamoto, Kasumi
AU - Kojima, Yuki
AU - Nishikawa, Tadaaki
AU - Tanioka, Maki
AU - Sudo, Kazuki
AU - Noguchi, Emi
AU - Murata, Takeshi
AU - Shiino, Sho
AU - Takayama, Shin
AU - Suto, Akihiko
AU - Ohe, Yuichiro
AU - Fujiwara, Yasuhiro
AU - Yonemori, Kan
N1 - Funding Information:
This study was supported by the Jikei University Research Fund for Graduate Students.
Funding Information:
Tadaaki Nishikawa reports personal fees from Takeda Pharmaceutical Company, EISAI, and AstraZeneca, outside the submitted work. Emi Noguchi reports personal fees from Pfizer, Taiho, Eli Lilly, AstraZeneca, Chugai, and EISAI, outside the submitted work. Yuichiro Ohe reports grants and personal fees from AstraZeneca, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Janssen, Kyorin, Nippon Kayaku, Novartis, Ono Pharmaceutical Company, MSD, Pfizer, Taiho, and Takeda Pharmaceutical Company, personal fees from Boehringer Ingelheim and Celtrion, and grants from Kissei, outside the submitted work. Yasuhiro Fujiwara reports personal fees from AstraZeneca, Chugai, Daiichi Sankyo, Bristol-Myers, SRL, and Santen, outside the submitted work. Kan Yonemori reports personal fees from Pfizer, AstraZeneca, EISAI, Takeda Pharmaceutical Company, Chugai, Ono Pharmaceutical Company, Novartis, and Daiichi Sankyo, outside the submitted work. All remaining authors declare no potential conflicts of interest.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - Purpose: Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown. Methods: We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin–eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology. Results: Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ2 = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48–0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57–11.99, p = 0.005). Patients with high CD8/PD–L1 (–) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1(+) tumors had the worst prognosis (5 year iDFS, 33.3%). Conclusion: CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8–positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC.
AB - Purpose: Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown. Methods: We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin–eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology. Results: Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ2 = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48–0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57–11.99, p = 0.005). Patients with high CD8/PD–L1 (–) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1(+) tumors had the worst prognosis (5 year iDFS, 33.3%). Conclusion: CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8–positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC.
KW - Chemotherapy
KW - Prognosis
KW - Programmed cell death-ligand 1
KW - Triple-negative breast cancer
KW - Tumor-infiltrating lymphocytes
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UR - http://www.scopus.com/inward/citedby.url?scp=85141986303&partnerID=8YFLogxK
U2 - 10.1007/s10549-022-06787-x
DO - 10.1007/s10549-022-06787-x
M3 - Article
C2 - 36385236
AN - SCOPUS:85141986303
SN - 0167-6806
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
ER -
