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01.12.2014 | Preclinical study | Ausgabe 3/2014

Breast Cancer Research and Treatment 3/2014

Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 3/2014
Autoren:
Minoru Miyashita, Hironobu Sasano, Kentaro Tamaki, Monica Chan, Hisashi Hirakawa, Akihiko Suzuki, Hiroshi Tada, Go Watanabe, Noriko Nemoto, Saki Nakagawa, Takanori Ishida, Noriaki Ohuchi
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10549-014-3197-y) contains supplementary material, which is available to authorized users.

Abstract

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.

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Supplementary material 1 (TIFF 1067 kb)
10549_2014_3197_MOESM1_ESM.tif
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