PD-1/PD-L1 pathway: Current research in breast cancer.

INTRODUCTION: Immunotherapy has shown encouraging outcomes in breast cancer (BC) treatment in recent years. The programmed cell death ligand 1 (PD-L1) transmembrane protein is suggested to function as a co-inhibitory factor in the immune response, where it collaborates with programmed cell death protein 1 (PD-1) to stimulate apoptosis, suppress cytokine release from PD-1 positive cells, and limit the growth of PD-1 positive cells. Furthermore, in many malignancies, PD-L1 reduces the immune system's response to neoplastic cells. These observations suggest that the PD-1/PD-L1 axis plays a vital role in cancer therapy and the regulation of cancer immune escape mechanisms. This review aimed to provide an overview of the functions of PD-1 and PD-L1 in BC cancer therapy. METHODS: This research design is a literature review. The style is a traditional review on topics or variables relating to the PD-1/PD-L1 pathway. A literature search was carried out using three online databases. RESULTS: The search using the keywords yielded a total of 248 studies. Each result was filtered again according to the inclusion and exclusion criteria, resulting in a final total of 4 studies to be included in the literature review. CONCLUSIONS: The combination of PD-1/PD-L1 is essential for many malignancies. According to the evidence presented, this combination presents both an opportunity and a challenge in cancer treatment. Since many solid cancers, especially BC, express high levels of PD-1/PD-L1, cancer treatment mainly involves targeted therapies.

Pleiotrophin serum level and metastasis occurrence in breast cancer patients.

BACKGROUND: Breast cancer (BC) cases in Makassar, Indonesia, are on the rise, with 2723 cases recorded in 2018. Tumor cells in the blood indicate metastasis, emphasizing the need for early diagnosis and monitoring. Pleiotrophin (PTN) is associated with various human malignancies, and recent studies suggest a correlation between PTN expression and advanced BC stages; therefore, PTN could serve as an independent predictor of metastasis. This study aimed to determine the correlation between serum PTN level, histopathological grading, and metastasis occurrence in BC patients in Makassar, Indonesia. METHODS: This study used an observational cross-sectional design. Pleiotrophin serum levels were examined using enzyme-linked immunosorbent assays. This study used a t-test and ROC curve analysis for the statistical tests. RESULTS: Of the 64 samples used in this study, metastasis was present in 26 cases and absent in 38 samples. The mean PTN serum levels in metastatic and non-metastatic breast cancer patients were 4.311 and 1.253, respectively. The PTN receiver operating characteristic curve showed an area under the curve of 2.47 ng/dL, which was statistically significant (p < 0.001). A significant relationship was found between PTN level and metastasis (p < 0.001). The correlation coefficient was 0.791, indicating a positive correlation. CONCLUSION: This study revealed that the serum PTN level among breast cancer patients had a cut-off value of 2.47 ng/dL. The research established a clear correlation between PTN level and metastasis occurrence in breast cancer patients, indicating a higher likelihood of distant metastasis with elevated PTN concentration.

Comparison of tumor size, histopathological grade, and molecular subtype of breast cancer at a single center study.

BACKGROUND: Breast cancer (BC) is the second most frequent cancer-related death among women worldwide. Factors influencing BC patients' survival include histopathological grade, histopathological type, stage, hormonal receptors, and number of mitotic images. OBJECTIVE: To compare the tumor size, histopathological grade, and molecular type of BC patients. METHODS: This was an observational analytic retrospective study. The population was BC patients at Dr. Wahidin Sudirohusodo Hospital from 2017 to 2021. The Kruskal-Wallis test was used to compare statistically between tumor size, histopathological grade, and molecular subtype. Significance was set at p < 0.05. RESULTS: The study included 784 patients. Most were aged 50-59 years (34.8%), with tumor size 4c (37.0%) and moderate grade (66.1%), and the most common molecular subtype was luminal A (34.2%). Bivariate analysis using the Kruskal-Wallis test found no significant difference in molecular subtypes based on tumor size (p = 0.079), but significant differences existed in molecular subtype by histopathological grade (p = 0.005) and tumor size by histopathological grade (p < 0.001). CONCLUSIONS: Significant differences existed between histopathological grade by tumor size and molecular subtype. Early diagnosis and prompt treatment of BC patients are important to prevent morbidity and mortality.

Comparison of outcomes in patients with luminal type breast cancer treated with a gonadotropin-releasing hormone analog or bilateral salpingo-oophorectomy: A cohort retrospective study.

Introduction: Premenopausal patients with hormone receptor-positive breast cancer require ablation therapy via a pharmacological or surgical approach. Data comparing outcomes between treatment with gonadotropin-releasing hormone (GnRH) analogs and treatment with bilateral salpingo-oophorectomy (BSO) in Indonesia remains limited. Therefore, this study aimed to compare incidence of local recurrence and metastasis, and overall survival (OS) in patients with luminal type breast cancer treated using the two approaches. Methods: This observational retrospective cohort study examined 100 premenopausal patients diagnosed with luminal type hormone receptor-positive breast cancer who registered at Dr. Wahidin Sudirohusodo Hospital and its networking hospitals in Makassar City from January to December 2017. Result: Among the 100 study patients, 50 were given GnRH analogs and 50 underwent BSO. Incidence of local recurrence (P = 0.408) and metastasis (P = 0.419) did not significantly differ between the GnRH analog and BSO groups, although the incidence of local recurrence was higher in the GnRH analog group (68% vs. 58%) and incidence of metastasis was higher in the BSO group (24% vs 19%). The 5-year survival rate did not significantly differ between the GnRH analog and BSO groups. Conclusion: Incidence of local recurrence and metastasis, and 5-year survival rate did not significantly differ between premenopausal breast cancer patients treated using a GnRH analog and those treated with BSO. Further large-scale studies to compare the efficacy and safety of both approaches are warranted.

Vascular endothelial growth factor-A expression is significantly correlated with HER2 expression in late-stage breast cancer patients.

BACKGROUND: Molecular marker analysis has become important in breast cancer diagnosis and treatment and may reveal new mechanisms in breast cancer pathogenesis. Aside from the commonly used hormonal receptors and HER2, VEGF-A has been increasingly shown to be important in breast cancer diagnosis and pathogenesis. OBJECTIVE: This study aimed to determine the relationship between VEGF-A expression on ER and PR and HER2 hormonal status in patients with late-stage breast cancer (locally advanced or with distant metastases). METHODS: This observational, cross-sectional study examined VEGF-A expression and molecule markers (ER, PR, and HER2) of breast cancer tissue using immunohistochemistry. The Chi-square test was used to determine whether two categorical variables were correlated. Statistical significance was set at p < 0.05. RESULTS: VEGF-A showed no significant correlation with demographic characteristics, TNM staging, pathological grading, luminal or non-luminal type, or hormonal receptor markers but showed a significant positive correlation with HER2 receptors (p = 0.036). CONCLUSIONS: VEGF-A was positively correlated with HER2 expression in breast tumor tissue but showed no significant correlation with other breast cancer markers, including luminal typing or hormonal receptors. Further study is needed to understand the mechanistic interplay between VEGF and HER2 in breast cancer pathogenesis.

Platelet count and breast cancer stage.

INTRODUCTION: The relationship between increased platelet count and cancer classification stage has long been established. The prevalence of thrombocytosis varies from 10% to 57% in cancer patients. The pathogenesis of thrombocytosis in malignancy is uncertain. However, there is evidence that tumor cells secrete humoral factors that can cause thrombocytosis. Preoperative thrombocytosis is a poor prognostic variable in malignancies. This study investigated the correlation between platelet count and breast cancer stage. METHODS: This cross-sectional study was conducted from February 2020 to January 2021. Patient data were collected from medical records. The study population comprised breast cancer patients at Dr. Wahidin Sudirohusodo Makassar. The staging examinations were based on the tumor, node, metastasis (TNM) classification according to the American Joint Committee on Cancer (AJCC) 8th Edition. RESULTS: The study group comprised 171 breast cancer patients of varying ages. Metastasis was present in five (2.92%) patients and absent in 166 (97.8%) patients. Analyses found no statistically significant differences between the three staging groups based on the platelet count (p = 0.952). CONCLUSION: There was no statistically significant relationship between increased platelet count and staging according to the TNM classification in breast cancer patients.

The expression of programmed death-ligand 1 and its association with histopathological grade, stage of disease, and occurrence of metastasis in breast cancer.

INTRODUCTION: Programmed death ligand 1 (PD-L1) plays a role in tumor escape and progression by inactivating T lymphocytes. The aim of the study reported here was to determine the relationship between the expression of PD-L1 and histopathological grade, stage of disease, and the occurrence of metastasis in breast cancer. METHODS: The observational cross-sectional study involved analyzing the expression of PD-L1 by immunohistochemistry. RESULTS: PD-LI was expressed in 43 of 60 patients with breast cancer (71.6%), mostly with a moderate histopathological grade (58.3%) and at an advanced stage (50%). Associations between the expression of PD-L1 and histopathological grade (p = 0.011), stage of disease (p = 0.009), and the occurrence of metastasis (p = 0.01) were significant, with an odds ratio of 5. CONCLUSION: The associations between the expression of PD-L1 and histopathological grade, disease stage, and occurrence of metastasis were all significant in cases of breast cancer in the sample. Those findings suggest that the expression of PD-L1 increases the progression of breast cancer.

Overexpression of NF-kB as a predictor of neoadjuvant chemotherapy response in breast cancer.

BACKGROUND: Cancer cells can defend themselves against apoptosis by activating NF-κB. Nuclear factor-kappa B (NF-κB) activity has also been associated with chemotherapy resistance. OBJECTIVE: We aimed to investigate the relationship between NF-κB expression and intrinsic subtypes and anthracycline-based neoadjuvant chemotherapy responses in patients with locally advanced breast cancer. METHODS: This prospective cohort study examined NF-κB expression and intrinsic subtypes of breast cancer tissue using immunohistochemistry (IHC). We conducted descriptive statistical analyses as well as survival analyses. RESULTS:  The study sample was 63 patients, of which 21 cases (33.33%) were responsive to neoadjuvant chemotherapy, and 42 cases (66.7%) were non-responsive. There is a significant relationship between negative ER, negative PR, grading, and high Ki67 expression with NF-κB overexpression (p < 0.05). No significant relationship was found between intrinsic subtypes and HER2 with NF-κB expression (p > 0.05). A significant relationship was found between NF-κB expression and responsive chemotherapy results (p < 0.01). CONCLUSION: In locally advanced breast cancer, there is a correlation between NF-B expression and response to anthracycline-based neoadjuvant chemotherapy. Patients who express NF-KB have a better response to chemotherapy than those who overexpress NF-kB.

Relationship between body mass index and cholesterol levels with histopathological grading of breast cancer.

BACKGROUND: Breast cancer, a global health problem with a high mortality rate, has several risk factors, including obesity and increased lipid profile. Postmenopausal obesity is associated with estrogen production from adipose tissue, while abnormal cell growth is triggered by insulin-like growth factor 1 (IGF-1) and insulin. Obesity could be assessed by measuring body mass index (BMI). An increase in lipid profile signifies an increased risk for breast cancer. Histopathological findings in the form of grading and differentiation can indicate how serious the condition is. Breast cancer with good differentiation is always associated with a positive prognosis. OBJECTIVE: This observational analytic study aims to determine the relationship between BMI and cholesterol levels based on the menopausal status and the histopathological grading findings of breast cancer patients. METHODS: The observational cross-sectional study analyzed histopathological grading, total cholesterol level, and body mass index. Data were analyzed with Spearman rank correlation statistical test, and the results are significant when the p-value is <0.05. RESULTS: Analyzing the relationship between cholesterol levels and histopathological gradings indicated a moderate correlation. The results of another correlation test based on menopausal status showed a weak correlation value, while menopause was said to be significant, indicating a moderate correlation. However, results from the analysis of BMI data in the menopausal subject group were associated with histopathological assessment. CONCLUSIONS: There is a relationship between cholesterol levels and histopathological degrees in the two menopausal status groups. However, no relationship was found between BMI and the histopathological grades of breast cancer.