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

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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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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.

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Authors and Affiliations

  1. Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Minoru Miyashita, Akihiko Suzuki, Hiroshi Tada, Go Watanabe, Noriko Nemoto, Saki Nakagawa, Takanori Ishida & Noriaki Ohuchi

  2. Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Minoru Miyashita, Hironobu Sasano, Kentaro Tamaki, Monica Chan, Noriko Nemoto & Saki Nakagawa

  3. Department of Breast Surgery, Nahanishi Clinic, 2-1-9 Akamine, Naha, 901-0154, Japan

    Kentaro Tamaki

  4. Department of Breast Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, 980-0803, Japan

    Hisashi Hirakawa

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  1. Minoru Miyashita
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  2. Hironobu Sasano
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Correspondence to Minoru Miyashita.

Electronic supplementary material

Supplementary Figure Pathological complete response (pCR) rates of TNBC tumors by the clinicopathological factors, including basal-like status, Ki-67 labeling index (LI), Vasohibin-1, CD31 and vasohibin-1 positive ratio (VPR). HG: histological grade.

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Miyashita, M., Sasano, H., Tamaki, K. et al. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat 148, 525–534 (2014). https://doi.org/10.1007/s10549-014-3197-y

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