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Background: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi. Methods: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data. Results: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m². In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L). Conclusion: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs) were found to be associated with a better clinical outcome in specific subtypes of breast cancer. Aim: To study the association between TILs and the prognosis of Egyptian patients with HER2-negative breast cancer metastatic to the viscera. Methods: This prospective study included 100 patients with HER2-negative metastatic breast cancer. Intratumoral TILs, stromal TILs, and CD4 and CD8 were examined in the pathological specimens and their relationship with survival and response to treatment was studied. Results: At a median follow-up period of 43 months, the median overall survival was 44.7 months (95%CI: 39.2-50.2) and the 5-year overall survival rate was 28%. A high level of CD8+ve TILs was associated with significantly longer overall survival (p < 0.001) and progression-free survival (p=0.043). There was no significant correlation between intratumoral TILs, stromal TILs, or CD4+ve and overall survival. Conclusions: A higher level of CD8+ve TILs is associated with better overall as well as progression-free survival in HER2-negative breast cancer with visceral metastases.

Background: Tumor-infiltrating lymphocytes (TILs) were found to be associated with a better clinical outcome in specific subtypes of breast cancer. Aim: To study the association between TILs and the prognosis of Egyptian patients with HER2-negative breast cancer metastatic to the viscera. Methods: This prospective study included 100 patients with HER2-negative metastatic breast cancer. Intratumoral TILs, stromal TILs, and CD4 and CD8 were examined in the pathological specimens and their relationship with survival and response to treatment was studied. Results: At a median follow-up period of 43 months, the median overall survival was 44.7 months (95%CI: 39.2-50.2) and the 5-year overall survival rate was 28%. A high level of CD8+ve TILs was associated with significantly longer overall survival (p<0.001) and progression-free survival (p=0.043). There was no significant correlation between intratumoral TILs, stromal TILs, or CD4+ve and overall survival. Conclusions: A higher level of CD8+ve TILs is associated with better overall as well as progression-free survival in HER2-negative breast cancer with visceral metastases. [ABSTRACT FROM AUTHOR]

Aim: In this paper, we present a prospective observational study, which determines the incidence of bone metastases and its correlation with hormonal receptors (estrogen receptor [ER]/progesterone receptor [PR]) and human epidermal growth factor receptor 2 (HER2) in breast cancer.Materials and Methods: From October of 2015 to July 2017, 262 patients were eligible for the study, of which 98 patients presented/developed bone metastases. ER/PR and HER2 receptor status were determined, and bone scintigraphy with a technetium-99 m was carried out on each patient during the study.Results: The incidence rate of bone metastases as found in this study was 25.25%, and the mean and median age at diagnosis were 47.23 and 46, respectively (age range = 28-80). Bone metastases were more prevalent in ER-positive tumors (P = 0.043), tumors with lymph node positivity (P = 0.002), and lower grade tumors (P = 0.002), whereas visceral metastases were more common with ER-tumors (P = 0.005), tumors with higher grade (P = 0.012), and tumors with lymph node positivity (P = 0.034). In this study cohort, the spine and pelvis were the most commonly involved subsites of bone metastases (P < 0.001).Conclusion: This study demonstrates that the metastatic patterns in breast cancer strongly correlate with various breast cancer subtypes, mainly designated by ER, PR, and HER2. Hormone receptor-positive tumors show a predilection for bones as the first site of relapse compared to hormone-receptor-negative tumors which have a proclivity to develop as visceral metastases. [ABSTRACT FROM AUTHOR]

Purpose: We developed and validated algorithms to identify metastases and breast cancer recurrence in Danish medical registries. We computed the incidence rate (IR) and hazard ratios (HRs) to evaluate predictors of these outcomes in stage II/III breast cancer patients.Methods: We included all women in Denmark diagnosed during 1999–2011 with regional or stage II/III breast cancer. Demographic, tumor, and treatment data were ascertained from population-based health registries. To facilitate diagnostic work-up of the primary cancer, follow-up began 180 days after diagnosis and continued until recurrence/metastases, death, or 31 December 2012, whichever occurred first. We computed the positive predictive values (PPVs) of recurrence, bone metastases, and visceral metastases using medical records as a gold standard. We calculated the cumulative incidence, IR per 10,000 person years, and used Cox regression to compute the HRs and associated 95% confidence intervals (95% CI) for each outcome.Results: Among 23,478 patients, 7073 had regional stage and 16,405 had stage II/III breast cancer. The PPV for recurrence was 72.6% (95% CI 59.3, 83.3%). The PPVs for bone and visceral metastases were 92.3% (95% CI 69.3–99.2%) and 70.8% (95% CI 51.1, 85.9%), but had low sensitivity. Five-year cumulative incidence of recurrence, bone metastases, and visceral metastases were 18.4, 2.2, and 5.2%, with corresponding 5-year IRs of 540 (95% CI 524, 557), 60 (95% CI 55, 65), and 144 (95% CI 136, 152), respectively. Predictors of recurrence and metastases included age, stage, hormone receptor status, and cancer treatment.Conclusion: Our algorithms show moderate to high PPVs for recurrence and metastases. The IRs of metastases were lower compared with other registry-based cohort studies, so may be underestimated in Danish registries. [ABSTRACT FROM AUTHOR]

Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B ( HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone. © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m2 on day 1, and capecitabine (Xeloda) 2,000 mg/m2/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with ≥3 chemotherapy lines. A median of 6 cycles were given (range 1–19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0–50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The efficacy of fulvestrant (Faslodex™), a novel oestrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, was compared with the aromatase inhibitor anastrozole (Arimidex™) for the second-line treatment of advanced breast cancer in postmenopausal women with visceral and non-visceral metastases. Assessment was by means of a retrospective subgroup analysis of combined data from two randomised, phase III trials. Objective response (OR) rates were similar in patients treated with fulvestrant and anastrozole, respectively (21.9% versus 19.3%—patients with no visceral metastases; 15.7% versus 13.2%—all of the patients with visceral metastases; 18.8% versus 14.0%—patients with visceral metastases only). The proportion of patients with clinical benefit (CB) was also similar between treatments and between subgroups with and without visceral disease. Fulvestrant is at least as effective as anastrozole, providing a valuable treatment option for advanced breast cancer in postmenopausal women with visceral metastases who have failed on prior endocrine therapy. [Copyright &y& Elsevier]