Prognostic significance of transforming growth factor ß receptor II in clinical stage III breast cancer patients - a pilot study.

BACKGROUND: Transforming growth factor-ß (TGFß) has a dual function in breast cancer, having a tumor suppressor activity in early carcinomas while enhancing tumor metastasis in advanced breast carcinoma. Consequently, the prognostic role of TGFß and its signaling cascade in breast cancer remain unclear. OBJECTIVE: To investigate the relationship between TßRII expression, clinic-pathological characteristics, and prognostic significance of TßRII expression in clinical stage III breast cancer. METHODS: Biopsy from the primary tumor was obtained from 30 newly diagnosed clinical stage III breast cancer patients before receiving any therapy. Expression of TßRII, ER, PR, Her2 and Ki-67 was assessed by immunohistochemistry. RESULTS: TßRII expression was positive in 66.7% of cases and was significantly associated with advanced nodal stage and distant metastases. After a median follow up of 42.3 months, TßRII was associated with poor disease-free survival and it was an independent factor for predicting the poor outcome for breast cancer patients, especially in node positive tumors, ER/PR positive and Her2-negative tumors. CONCLUSIONS: These findings suggest the usage of therapeutic drugs that target TGFß in advanced breast cancer patients may be effective. Nevertheless, blockage of the tumor promoting and sparing of the tumor suppressor effect of TGFß pathway should be taken into consideration. We suggest that these therapies might have more benefit in ER and PR positive tumors.

Clinical Impact of Breast Cancer Stem Cells in Metastatic Breast Cancer Patients.

BACKGROUND: Breast tumors are composed of phenotypically diverse groups of cells; however, it is unclear which of these cells contribute to tumor development. Breast cancer management usually targets proliferating cells, but as breast cancer stem cells are slowly cycling, they may escape these targets whenever they are not actively proliferating. This may explain the occurrence of recurrences and failure of the treatment. AIM: To assess the impact of the BCSC expression on progression-free survival (PFS), overall survival (OS), and tumor response in metastatic breast cancer patients and to correlate the BCSC expression with different clinicopathological parameters. MATERIAL: This prospective study enrolled 76 de novo metastatic breast cancer patients recruited from the Oncology Center, Mansoura University, Egypt, with a minimum age 31 years and a maximum of 70 years. Pretreatment BCSC markers (CD44 and CD24) were assessed by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissues from a primary or metastatic site. Patients received different lines of treatment, hormonal or chemotherapy, according to their biological subtypes. Anti-Her2 was added for Her2-positive patients. RESULTS: Thirty-three patients (43.4%) were premenopausal and 43 patients (56.6%) were postmenopausal. Bone-only metastasis was seen in 12 patients (15.7%), however, visceral ± bone metastasis was seen in 64 patients (84.3%). BCSC markers (CD44+ve and CD24-ve) were expressed in 32 patients (42.1%), while 44 patients (57.9%) were not expressing BCSC markers. Out of 32 patients expressing BCSC, 22 patients (68%) were premenopausal and 28 patients (87.5%) were with high-grade (GIII) disease. BCSC was significantly presented in triple negative subtype breast cancer as there were 32 patients with the BCSC expression, and out of them, 15 patients (46.9%) had triple negative disease, 10 patients (31.3%) had luminal subtype, and seven patients (21.9%) were Her2-amplified, while there were 44 patients without BCSC expression, and out of them, 30 patients (68.2%) were of the luminal subtype, no patient (20.5%) had triple negative disease, and five patients (11.4%) were Her2-amplified (P 0.006). Twenty-four patients (31.5%) presented with visceral crisis; out of them, 17 patients (70.1%) were expressing BCSC which also denoted more aggressive disease. Seventy-four patients were candidates for the response assessment. BCSC-expressing patients showed poor response compared to non-BCSC (16.1% responsive versus 51.2%, respectively), with a significance relation (P 0.003). The BCSC expression was associated with both significant short PFS (median, 18 months vs. 35 months; P=0.001) and short OS (median, 26 months vs. 43 months; P=0.003). In multivariate analysis; BCSC expression was an independent prognostic factor for poor OS (P=0.055) along with the molecular subtype (P=0.012), Her2 status (P=0.011), and histologic grade (P=0.037). CONCLUSION: This study further validates the BCSC expression as a poor prognostic biomarker correlated with poor response, short PFS and OS. So, it could be used as a marker for tailoring treatment with different lines of therapies in further studies. The BCSC expression was highly presented in the triple negative subtype which is an aggressive disease that lacks different targets. So, targeting BCSC may carry a hope in future for this group of patients.

Computed Tomography Assessment of Hepatic Metastases of Breast Cancer with Revised Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1): Inter-Observer Agreement.

BACKGROUND: To assess inter-observer agreement of revised RECIST criteria (version 1.1) for computed tomography assessment of hepatic metastases of breast cancer. MATERIAL/METHODS: A prospective study was conducted in 28 female patients with breast cancer and with at least one measurable metastatic lesion in the liver that was treated with 3 cycles of anthracycline-based chemotherapy. All patients underwent computed tomography of the abdomen with 64-row multi- detector CT at baseline and after 3 cycles of chemotherapy for response assessment. Image analysis was performed by 2 observers, based on the RECIST criteria (version 1.1). RESULTS: Computed tomography revealed partial response of hepatic metastases in 7 patients (25%) by one observer and in 10 patients (35.7%) by the other observer, with good inter-observer agreement (k=0.75, percent agreement of 89.29%). Stable disease was detected in 19 patients (67.8%) by one observer and in 16 patients (57.1%) by the other observer, with good agreement (k=0.774, percent agreement of 89.29%). Progressive disease was detected in 2 patients (7.2%) by both observers, with perfect agreement (k=1, percent agreement of 100%). The overall inter-observer agreement in the CT-based response assessment of hepatic metastasis between the two observers was good (k=0.793, percent agreement of 89.29%). CONCLUSIONS: We concluded that computed tomography is a reliable and reproducible imaging modality for response assessment of hepatic metastases of breast cancer according to the RECIST criteria (version 1.1).

Pomegranate protects liver against cecal ligation and puncture-induced oxidative stress and inflammation in rats through TLR4/NF-κB pathway inhibition.

Acute liver injury secondary to sepsis is a major challenge in intensive care unit. This study was designed to investigate potential protective effects of pomegranate against sepsis-induced acute liver injury in rats and possible underlying mechanisms. Pomegranate was orally given (800mg/kg/day) for two weeks before sepsis induction by cecal ligation and puncture (CLP). Pomegranate improved survival and attenuated liver inflammatory response, likely related to downregulation of mRNA expression of toll like recptor-4, reduced nuclear translocation and DNA binding activity of proinflammatory transcription factor NF-κB subunit p65, decreased mRNA and protein expression of tumor necrosis factor-alpha and reduction in myeloperoxidase activity and mRNA expression. Pomegranate also decreased CLP-induced oxidative stress as reflected by decreased malondialdehyde content, and increased reduced glutathione level and superoxide dismutase activity. These results confirm the antiinflammatory and antioxidant effects of pomegranate in CLP-induced acute liver injury mediated through inhibiting TLR4/NF-κB pathway, lipid peroxidation and neutrophil infiltration.