Prognostic Value of Tumor Infiltrating Lymphocytes in Locally Advanced HER2 Enriched Breast Cancer.

PURPOSE: We aim to study the association between stromal tumor infiltrating lymphocytes (TILs) level and disease free survival (DFS) in a group of ER and PR negative, HER2+ locally advanced breast cancer patients who underwent curative intent surgery. METHODS: This is a retrospective cohort study including 66 locally advanced hormone receptor-negative; HER2+ breast cancer patients presented between 2013 and 2015 at NCI-Cairo, Egypt. Enrolled patients had at least clinically T3 and/or node positive disease either clinically or radiologically. Metastatic workup included CT and bone scans or PET-CT. Patients with hormone receptor positive, HER2 negative, inadequate paraffin block and who lost follow up before or immediately after curative surgery were excluded. Patients were followed from breast surgery till relapse date for a minimum of 36 months. TILs and CD8 antigen were assessed on paraffin-embedded blocks using immunohistochemistry. RESULTS: Patients with a median age of 52 years presented with clinical T3 stage (53%) and N1 stage (61%). Modified radical mastectomy was performed in 79%. Only 41% received neoadjuvant chemotherapy and 56% received trastuzumab. TILs were 50, 17 and 33% for absent, intermediate and extensive groups and CD8+ lymphocytes were present in 80% of cases. At the end of follow-up period, 23 patients (35%) were found to have disease recurrence either loco-regional (22%) or distant (78%). TILs were 14, 4 and 5% for absent, intermediate and extensive respectively; while CD8+ lymphocytes were absent in 6% and present (≥1%) in 17%. Higher DFS was recorded for patients with extensive TILs level only who received trastuzumab. CONCLUSION: High TILs is good prognosis in HER2 enriched breast cancer provided that patients received HER2 directed therapy. Moreover, CD8+ lymphocytes are highly representative and maybe used as an alternative for TILs. We recommend considering TILs and specifically CD8+ as one of the risk factors that predict prognosis of HER2+ breast cancer.

Clinical impact of SNP of P53 genes pathway on the adult AML patients.

INTRODUCTION: Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes. AIM: To study the impact of p53, p21, and mdm2 gene polymorphisms on the clinical outcome in adult AML patients treated at the National Cancer Institute (NCI) - Cairo University. METHODS: Forty-eight adult AML patients presented to the Medical Oncology Department, NCI, from April 2010 till November 2011. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving P53, MDM2, and P21 single-nucleotide gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism coupled analysis. RESULTS: The mean age was 35.7 years. After a median follow-up period of 12 months, 28 patients (58.4%) achieved complete remission (CR) and the overall survival (OS) was 8.7 months. Patients with homozygous Arg/arg at codon 72 of P53 had a better median OS months than Arg/Pro and Pro/Pro (13.4 vs. 8.4 vs. 1.5 months, respectively; P = 0.045). P53/p21 combination had a better median OS and disease-free survival (DFS) of 12.1 and 13.7 months for wild type cases (GG + Ser/ser) and 20.3 and 20.7 months for patients with either variant genes (GC + Ser/arg) compared with 1.1 and 1.9 months for patients with both variant genes (CC + arg/arg), (P = 0.037 and 0.004). The presence of wild genotype of either P21 or MDM2 may abolish the effect of P53 homozygous variant genotype on the OS. Neither p21nor mdm2 polymorphism alone showed an impact on OS or DFS. CR was not affected by any of the three gene polymorphisms. CONCLUSION: The p53 pathway gene polymorphisms may affect the OS of adult AML patients.