Does a 40% Cut-off Point for Ki-67 Expression Have a Role in Identifying the Development of Distant Metastasis Within 2 Years in Locally Advanced Triple Negative Breast Cancer Patients?

Objective: Triple negative breast cancer (TNBC) has a higher proportion of patients with distant recurrence or metastasis. Ki-67 has been suggested as an essential factor in cancer grading and prognostic evaluation, although there is still a debate regarding the Ki-67 cut-off value in TNBC. The aim of this study was to determine the role of Ki-67 expression using a 40% cut-off point as a risk factor for developing distant metastasis within two years in patients with TNBC. Materials and Methods: This analytical observational study was conducted with a case-control design from January 2021-2022. Subjects were divided into two groups (metastasis within two years or more than two years after diagnosis). Bivariate analysis was conducted using chi-square test and odds ratio (OR) was also analyzed. Results: A total of 66 subjects were included. In patients with metastasized TNBC and a Ki-67 expression of ≥40%, 29 patients (55.8%) had metastasis occurring in ≤2 years and 23 patients (44.2%) had metastasis occurring in >2 years; in patients with metastasized TNBC and a Ki-67 expression of <40%, 4 patients (28.6%) had metastasis occurring in ≤2 years and 10 patients (71.4%) had metastasis occurring in >2 years. Chi-square analysis (p = 0.071) indicated no significant association between patients with Ki-67 expression of ≥40% and <40% with metastasis within 2 years [OR 3.152 (confidence interval: 95% 0.875-11.362)]. Conclusion: Ki-67 protein expression of over 40% in patients with locally-advanced TNBC does not indicate a greater risk of distant metastasis in the first two years after diagnosis.

Malignant adnexal tumor of the skin on breast: A case report of apocrine carcinoma.

INTRODUCTION: Malignant adnexal tumors of the skin (MATS) are a group of rare and varied tumors that lack standardized guidelines for their management. Apocrine carcinoma (AC) is a highly uncommon form of breast malignancy, contributing to less than 1 % of all female invasive breast carcinomas. AC has a similar microscopic growth pattern to invasive ductal carcinoma, which can result in early misdiagnosis. PRESENTATION OF CASE: This report presents a case of a 67-year-old female with a lump in the superior lateral quadrant of her left breast for six years. Surgical therapy was performed with wide excision due to clinical operability, no significant involvement of the axillary lymph nodes, and without metatasis. During the operation, Wide excision of 1-2 cm free margin according to standard and local reconstruction flaps were performed, with berry packing for the identified lymph nodes. DISCUSSION: The tumor was ER and PR negative, so hormonal treatment would be ineffective, assuming that this is an apocrine carcinoma of the breast. A metastatic work up was already done, and no metastasis was found. A mastectomy would appear to be a viable option. CONCLUSION: It is important to perform a clinical reevaluation to provide optimal treatment for breast malignancy. Misdiagnosis can occur early. In this case, a surgical procedure involving wide excision was performed, and as of now, the patient has not reported any recurrence.

Analysis of PD-L1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis in Asian Population.

OBJECTIVE: This study aimed to investigate the level of PD-L1 protein expression in patients with BCs who were of Asian descent. METHODS: Three databases were conducted on this article up to August 10th, 2022. The reference lists of the publications were examined for further studies, and in cases of duplicates, a study with a larger sample size was added. In survival analysis, the hazard ratio (HR) was applied to the circumstances characterized by the frequency of occurrences, and for the clinicopathological characteristic, the best-adjusted odds ratio (OR) with a 95% confidence interval (CI) was employed. The Newcastle-Ottawa Scale (NOS) was utilized to evaluate selection criteria, comparison, and exposure to establish the quality of the technique in the under-consideration studies. The Z test determined the association analysis of OS, DFS, and clinicopathological characteristics with PD-L1 expression. RESULT: All eight trials for OS and six for DFS were considered, with 4.111 and 3.071 participants, respectively. Overexpression of PD-L1 was linked to a reduced OS compared to individuals with undetectable expression (HR= 1.58, 95% CI 1.04-2.40; P=0.03). We analyzed clinicopathological features, and it elevated in individuals with histological grade III (OR=2.39, 95% CI 1.26-4.54; P=0.008) and positive node (OR=0.68, 95% CI 0.48-0.97; P<0.05). CONCLUSION: Overexpression of PD-L1 was associated with a shorter OS in BCs patients. High PDL1 was higher in persons with nodal positivity and histological grade III.

Does Trastuzumab Offer Good Value for Money for Breast Cancer Patients with Metastasis in Indonesia?

OBJECTIVE: Breast cancer is the most common cancer in Indonesia, with Indonesia's breast cancer mortality rate being the highest among Southeast Asian countries. This study aims to evaluate the cost-effectiveness and budget impacts of adding trastuzumab to chemotherapy versus chemotherapy alone for HER2-positive breast cancer patients in Indonesia. METHODS: We performed a Markov model-based economic evaluation to assess cost-effectiveness, cost-utility, and budget impact. Utility data, direct medical costs, and indirect costs were obtained primarily from interviewing patients. Clinical effectiveness data, on the other hand, were obtained from systematic reviews and real-world data and represented through progression free survival, overall survival, and quality-adjusted life years (QALYs). RESULT: From a healthcare provider's perspective, the total costs for the combined group were USD 14,516, while chemotherapy alone cost USD 7,489. While the cost-effectiveness analysis showed that the combination group had a higher total cost by USD 7,027, PFS was longer in the chemotherapy alone group, with a difference of 2.2 months. The ICER was USD 17,307 for every QALY gained. The total cost of adding trastuzumab over a 5-year period was USD 589 million. CONCLUSION: In conclusion, this economic evaluation suggests that the addition of trastuzumab to standard chemotherapy is not cost-effective in terms of PFS and OS compared with chemotherapy alone.
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The Association of Tumor-Infiltrating Lymphocytes and Programmed Cell Death 1 Expression with the Incidence of Distant Metastasis in Triple-Negative Breast Cancer Subjects in Sanglah General Hospital, Bali, Indonesia.

The triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a high rate of distant metastasis. The tumor immunity microenvironment plays an important role, including tumor-infiltrating lymphocytes (TIL) and PD-1 (programmed cell death 1)/PD-L1 (programmed cell death-ligand 1), in promoting TNBC aggressiveness. This study aimed to determine the association of TIL and PD-L1 expression with the incidence of distant metastasis in TNBC. This study is a cross-sectional study involving TNBC subjects at Sanglah General Hospital, Denpasar, conducted in 2019. The parameters analyzed were the expression of TIL, PD-L1, and the incidence of distant metastasis. The expression of TIL was analyzed histopathologically while PD-L1 was measured with Ventana PD-L1 kit test. Subject characteristics were obtained from medical records. Data were collected and analyzed by SPSS 22.0. As many as 31 subjects with TNBC were included in this study, with 51.6% subjects with distant metastasis. The majority of subjects with distant metastasis had low TIL and low tumoral PD-L1 but high PD-L1 stromal in TIL. From statistical analysis, only PD-L1 stromal in TIL expression was associated significantly with distant metastasis (p = 0.043). In conclusion, there was a significant association between PD-L1 stromal in TIL and the incidence of distant metastasis in TNBC.

Correlation of CD8+ Expression, Foxp3+ Expression, and CD8+/Foxp3+ Ratio with Triple Negative Breast Cancer Stage in Sanglah General Hospital.

BACKGROUND: Triple negative breast cancer (TNBC) is a breast cancer sub-type that lacks ER, PR and HER-2 expression. This type tends to be more aggressive than other types of breast cancer, with poor prognosis, distant metastases, higher recurrence rate, and lower overall survival. The TNBC is resistant to hormonal therapy, but generally very susceptible to chemotherapy. Expression of CD8+ and Foxp3+ were parts of the TIL, which often found in TNBC as an immune response to tumour antigens following antigens presenting cell (APC) stimulation. AIM: This study was conducted to find out whether the expression of CD8+, Foxp3+ and CD8+/Foxp3+ ratio was associated with the stage of TNBC. METHODS: This cross-sectional study was conducted from January 2014 until December 2016 at Sanglah Hospital with 46 research subjects. Two paraffin blocks were prepared for each sample to examine the CD8+ expression and Foxp3+ expression. Data were analysed using the Chi-Square test or Fisher's Exact tests as an alternative for bivariate analysis and logistic regression for multivariate analysis. RESULTS: On bivariate analysis, we found a low of CD8+ expression in advanced stage (p < 0.001 with OR 3.5; CI 1.611-7.727). Expression Foxp3+ in advanced stage (p = 0.482; OR 0.8; CI 0.497-1.374), while the ratio of CD8+/Foxp3+ (p = 0.213; OR 2.2; CI 0.650-7.132). On multivariate analysis, a low of CD8+ expression (adjusted OR 16.5; CI 3.735-7.370; p < 0.001) was obtained. CONCLUSION: Low expression of CD8+ was associated with the advanced stage of TNBC. The risk of becoming an advanced stage in TNBC patients with low CD8+ expression was 16.5 times higher than those with high of CD8+ expression. High expression of Foxp3+ was not associated with an advanced stage of TNBC. The low CD8+/Foxp3+ ratio was not associated with the advanced stage of TNBC.

Case Report: A Simple Thoraco - Abdominal Flap to Reconstruct Wide Defect of Radical Mastectomy in Squamous Cell Carcinoma of Breast.

BACKGROUND: Squamous cell carcinoma (SCC) of the breast is very unusual. Thoraco-abdominal (TA) flap is a simple flap, and it is a rotation advancement fasciocutaneous flap. Here, we present a case of using TA flap for chest wall reconstruction in quick in-quick outpatient. CASE PRESENTATION: A Russian woman 48 years old presented enlarging lump on her left breast for the last 5 years. She was diagnosed as stage IV low-differentiated breast cancer luminal B and had a history of 4 cycles chemotherapy. Patient getting worsening and no response to chemotherapy. We decided to perform palliative radical mastectomy to improve quality of life. Primary skin closure was not possible due to the wide defect of skin and soft tissue. We decided to use TA flap to cover the defect. Histopathology result was compatible with SCC. CONCLUSION: TA flap can be the choice in patients with a wide defect of skin and soft tissue after a radical mastectomy. Given its simplicity and shorter operative time, TA flap is an ideal option for quick in-quick outpatient.

Immunocytochemistry Test of Protein BRAF Expression for Diagnosis of Well Differentiated Thyroid Carcinoma.

BACKGROUND: Thyroid carcinoma generally has a good prognosis. The main focus of current research on thyroid carcinoma is to increase the accuracy of preoperative diagnosis of thyroid nodules. When the result of fine needle aspiration biopsy (FNAB) is indeterminate, clinicians often have doubts in determining the surgical management. OBJECTIVE: Protein BRAF expression analysis can help improve the accuracy of FNAB and optimize the management of differentiated thyroid carcinoma. METHODS: This study is a diagnostic test performed from October 2016 at Sanglah General Hospital with 38 patients as subjects who fulfilled the inclusion criteria. Data is being presented in descriptive form before diagnostic test is done to determine sensitivity, specificity, positive predictive value, negative predictive value and the accuracy of immunocytochemistry test for BRAF on indeterminate thyroid nodule. RESULTS: Thirty-eight samples met the inclusion criteria during the study period. Three samples were male (7.9%) and 35 samples (92.1%) were female. The mean age of the sample was 45.21 years (SD ±10.910 years) with ages ranging from 23 to 66 years. Of the 12 samples undergoing isthmolobectomy, 7 samples (58.4%) were determined to be malignant from histopathological results. The sensitivity value of BRAF immunocytochemistry test is 45.45% with a specificity value of 81.25%, a positive predictive value of 76.92%, a negative predictive value of 52% and an accuracy of 60.50%. Analysis of the receiver operator (ROC) curve shows the area under the curve (AUC) of 63.4% with a confidence interval of 45.5-81.2%. CONCLUSION: Immunocytochemistry BRAF test have a reliable diagnostic value and can be taken into consideration in the preoperative diagnosis of thyroid malignancies.