TY - JOUR
T1 - Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer
T2 - its correlation with pathological complete response to neoadjuvant chemotherapy
AU - Miyashita, Minoru
AU - Sasano, Hironobu
AU - Tamaki, Kentaro
AU - Chan, Monica
AU - Hirakawa, Hisashi
AU - Suzuki, Akihiko
AU - Tada, Hiroshi
AU - Watanabe, Go
AU - Nemoto, Noriko
AU - Nakagawa, Saki
AU - Ishida, Takanori
AU - Ohuchi, Noriaki
N1 - Funding Information:
Acknowledgments We wish to thank Yayoi Takahashi, MT, for her excellent technical assistance. This work was partly supported by a Grant-in-Aid for researches on the construction of treatment algorithm in triple-negative breast cancer (No. 26830094) from the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/11/25
Y1 - 2014/11/25
N2 - The anti-tumor immune response was recently reported to play a critical role in the chemotherapeutic sensitivity of breast cancer. Therefore, we investigated the correlation between CD8+ and FOXP3+ tumor-infiltrating lymphocytes and the pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), in conjunction with neoangiogenesis, basal and proliferation markers. CD8+ and FOXP3+ lymphocytes were assessed in biopsy specimens by double-staining immunohistochemistry, in combination with immunostaining of vasohibin-1, CD31, EGFR, CK5/6, and Ki-67. Earlier age, pre-menopausal status, smaller tumor size, and high Ki-67 were significantly associated with pCR, as in high CD8+, high CD8+/FOXP3+ ratio, and low vasohibin-1 positive ratio. Multivariate analysis did reveal that a high CD8+/FOXP3+ ratio was a strong predictor of pCR with an odds ratio of 5.32 (P = 0.005). High Ki-67 was also significantly associated with pCR (P = 0.002). TNBCs with a high CD8+/FOXP3+ ratio and high Ki-67 had the highest pCR rate (70 %) following NAC. However, the pCR rate of the patients with low CD8+/FOXP3+ ratio and low Ki-67 was only 5 %. The pCR rates of a high CD8+/FOXP3+ ratio and low Ki-67 patients and those with a low CD8+/FOXP3+ ratio and high Ki-67 were 24 and 21 %, respectively. TNBCs with a high CD8+/FOXP3+ ratio were more sensitive to anthracycline and taxane-based chemotherapeutic regimens, and the CD8+/FOXP3+ ratio in conjunction with Ki-67 could predict pCR following NAC in TNBC. This predictor may represent a new surrogate for testing the efficacy of investigational agents in the neoadjuvant setting.
AB - The anti-tumor immune response was recently reported to play a critical role in the chemotherapeutic sensitivity of breast cancer. Therefore, we investigated the correlation between CD8+ and FOXP3+ tumor-infiltrating lymphocytes and the pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), in conjunction with neoangiogenesis, basal and proliferation markers. CD8+ and FOXP3+ lymphocytes were assessed in biopsy specimens by double-staining immunohistochemistry, in combination with immunostaining of vasohibin-1, CD31, EGFR, CK5/6, and Ki-67. Earlier age, pre-menopausal status, smaller tumor size, and high Ki-67 were significantly associated with pCR, as in high CD8+, high CD8+/FOXP3+ ratio, and low vasohibin-1 positive ratio. Multivariate analysis did reveal that a high CD8+/FOXP3+ ratio was a strong predictor of pCR with an odds ratio of 5.32 (P = 0.005). High Ki-67 was also significantly associated with pCR (P = 0.002). TNBCs with a high CD8+/FOXP3+ ratio and high Ki-67 had the highest pCR rate (70 %) following NAC. However, the pCR rate of the patients with low CD8+/FOXP3+ ratio and low Ki-67 was only 5 %. The pCR rates of a high CD8+/FOXP3+ ratio and low Ki-67 patients and those with a low CD8+/FOXP3+ ratio and high Ki-67 were 24 and 21 %, respectively. TNBCs with a high CD8+/FOXP3+ ratio were more sensitive to anthracycline and taxane-based chemotherapeutic regimens, and the CD8+/FOXP3+ ratio in conjunction with Ki-67 could predict pCR following NAC in TNBC. This predictor may represent a new surrogate for testing the efficacy of investigational agents in the neoadjuvant setting.
KW - CD8
KW - Chemo-sensitivity
KW - FOXP3
KW - Ki-67
KW - Triple-negative breast cancer
KW - pCR
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UR - http://www.scopus.com/inward/citedby.url?scp=84911898296&partnerID=8YFLogxK
U2 - 10.1007/s10549-014-3197-y
DO - 10.1007/s10549-014-3197-y
M3 - Article
C2 - 25395319
AN - SCOPUS:84911898296
VL - 148
SP - 525
EP - 534
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 3
ER -