TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer.
The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, Beijing, 100853, China.
Hai-Ming
HM
Yu
Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, Beijing, 100853, China.
Jun-Lan
JL
Yang
Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, Beijing, 100853, China. jiaosc_301@sina.cn.
Shun-Chang
SC
Jiao
Department of General Surgery, General Hospital of Chinese People's Liberation Army, Beijing, 100853, China.
Jian-Dong
JD
Wang
Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, Beijing, 100853, China.
Ying
Y
Li
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000378:metabolism*; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D011498:Protein Precursors; D053773:Transforming Growth Factor beta1