title: Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis.
abstract: To examine the relationship between cytotoxic T lymphocyte antigen 4 (CTLA-4) expression and breast cancer prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded specimens of primary tumors from 130 patients with breast cancer who had a mean follow-up period of 112 months. CTLA-4 expressed in cytoplasm of breast cancer cells and in cytoplasm and cell membranes of interstitial lymphocytes. Univariate analysis (log-rank) associated higher density of interstitial CTLA-4(+) lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS. After controlling for age, clinical stage, Scarff-Bloom-Richardson grade, tumor thrombus, ER, PR, HER2 and Ki-67, multivariate analysis (Cox) showed that density of interstitial CTLA-4(+) lymphocytes independently predicted longer DFS (HR 0.315, P = 0.002) and OS (HR 0.313, P = 0.005), whereas tumor CTLA-4 expression independently predicted shorter DFS (HR 2.176, P = 0.029) and OS (HR 2.820, P = 0.007), i.e., patients with high CTLA-4(+) lymphocyte density and CTLA-4(low) tumor cells had the best prognoses. These results indicated that CTLA-4 expression in lymphocytes was associated with better prognosis, but that in tumor cells was associated with worse prognosis. Patients' CTLA-4 profiles might thus be used to predict the benefits and toxicity of CTLA-4 blockade.
authors.affiliation: Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Yu
authors.forename: Junlan
authors.initials: J
authors.lastname: Yang
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D060908:CTLA-4 Antigen / Q000096:biosynthesis / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human