PD-1 and PD-L1 Expression in Indian Women with Breast Cancer.

OBJECTIVE: The interaction between programmed cell death protein 1 (PD-1) on activated T-lymphocytes and programmed death-ligand 1 (PD-L1) on tumor cells or antigen-presenting cells sends immunosuppressive signals leading to the escape of tumor cells from the host anti-tumor immune response. Inhibiting this interaction with antibodies against PD-1 or PD-L1 is emerging as a valuable therapeutic strategy. However, tissue distribution patterns for PD-L1 and PD-1 in breast cancer patients from India are not reported, yet many clinical trials are underway. In this study the expression of PD-1 and PD-L1 in breast cancer patient samples from India was characterized. MATERIALS AND METHODS: The study included 392 cases of operated breast cancer (2012-2017) from a tertiary cancer care center in Bangalore, Karnataka, India. Paraffin blocks were retrievable and receptor status was known. Immunohistochemistry (IHC) was performed using anti-PD-L1 and anti-PD-1 antibodies. RNA was isolated from 76 fresh tumors and nine adjacent normal tissues (2019). PD-L1 transcript levels were measured by RT-qPCR using Hypoxanthine-guanine phosphoribosyl transferase (HPRT) as a reference gene. RESULTS: Based on IHC, PD-1 expression within tumor-infiltrating immune cells (TIICs) was observed in 55/385 cases (14%) across all breast cancer types. In triple-negative breast cancer (TNBC), 21/132 cases (16%) showed PD-1 staining in TIICs. The overall expression of PD-L1 in breast tumor cells across all breast cancer subtypes and TIICs was 11% (41/378) and 39% (151/385), respectively. A relatively higher proportion of TNBC cases had PD-L1 expression in tumor cells (17/132 cases, 13%) and immune cells (68/132 cases, 52%). We also detected PD-L1 transcript expression by qRT-PCR in freshly isolated tumor samples. CONCLUSION: These findings show that around 52% (68/132) of the TNBC cases express PD-L1 in TIICs. Hence, anti-PD-1/PD-L1 therapy alone or combined with chemotherapy may be a promising treatment for TNBC in Indian patients.

Metastatic hormone receptor-positive breast cancer in CDK 4/6 era: An outcome audit.

BACKGROUND: The treatment landscape of metastatic hormone receptor (HR) positive breast cancer has been changed in recent years. Availability of CDK 4/6 inhibitor and other hormone therapy has changed the treatment algorithm for these patient, we retrospectively analyzed our metastatic HR positive breast cancer patients. MATERIALS AND METHODS: In this study, we retrospectively analyzed the case records of hr positive metastatic breast cancer patient treated at department of medical oncology from October 2016 to September 2018. Demographical characteristics, site of metastasis, objective response and clinical benefit response and toxicity profile were analyzed. RESULTS: We treated a total of 178 patients of MBC with HT at our center during the study period. One hundred fifty-two patients received HT alone (control group) and 26 patients received HT and CDK 4/6 inhibitor (study group). The median age of patients was 56 and 58 years in the control group and study group. The ORR was 41.7 versus 57.9 (95% CI [1.01-2.56]), and the CBR was 66.1% versus 78.9%; (CI [1.18-3.56]) (P < 0.05) of the patients in control and study groups, respectively. CONCLUSIONS: Among patients with HR-positive, advanced breast cancer, hormone therapy is efficacious addition of CDK 4/6 inhibitor improve the efficacy with tolerable side effects.

Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: Case report and review of literature.

Leukocytosis may be found in patients with lung cancer either at time of diagnosis or during the course of the disease. Though mild leukocytosis is common in lung cancer, hyperleukocytosis defined as total leukocyte count more than 100,000 is uncommon. We describe a 68-year-old chronic smoker who presented with osteolytic pelvic bone lesion and hyperleukocytosis, who on evaluation was found to have a primary lung cancer. Bone marrow aspiration and biopsy showed marked myeloid hyperplasia. Myeloid series comprised predominantly mature neutrophils and stab forms. Cytogenetic investigation showed a normal chromosome set (46, XY). Repeated cultures from blood, urine, and sputum were sterile. He was started on chemotherapy but had a progressive downhill course. In patient with lung cancer, leukocytosis can be due to infection, use of corticosteroid or hematopoetic growth factors, bone marrow involvement, or paraneoplastic manifestation. Paraneoplastic leukocytosis is associated with poor prognosis and aggressive disease.