Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression

• Published in: Journal of translational medicine Vol. 16; no. 1; p. 87
• Main Authors: Asano, Yuka, Kashiwagi, Shinichiro, Goto, Wataru, Takada, Koji, Takahashi, Katsuyuki, Morisaki, Tamami, Fujita, Hisakazu, Takashima, Tsutomu, Tomita, Shuhei, Ohsawa, Masahiko, Hirakawa, Kosei, Ohira, Masaichi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.04.2018; BioMed Central; BMC
• Subjects: Adjuvant chemotherapy; Breast cancer; Chemotherapy, Adjuvant; Disease-Free Survival; Drug therapy; Gene expression; Genetic aspects; Humans; Immune checkpoint; Middle Aged; Multivariate Analysis; Neoadjuvant chemotherapy; Neoadjuvant Therapy; Neoplasm Proteins - metabolism; Pathological complete response; Patient outcomes; PD-1; PD-L1; Physiological aspects; Treatment Outcome; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - immunology; Triple-negative breast cancer; Japan; Neoadjuvant chemotherapy; PD-L1; Pathological complete response; Immune checkpoint; PD-1; Triple-negative breast cancer
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1458-y

"Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479). PD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC.