Oncological Safety of Breast Conservation Surgery in Young Females.

Breast conservation surgery (BCS) is the standard of care in early breast cancer. The oncological safety of this procedure has been proven beyond doubt in several randomised control trials. But there are concerns regarding the safety of this procedure in young females. The concern is regarding increased risk of local recurrence. This issue has not been addressed in any major trial. In this prospective study we intend to look into the oncological safety of BCS in young patients who are less than forty years of age.

Progesterone regulates the proliferation of breast cancer cells - in vitro evidence.

Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase. TOB-1 is a tumor suppressor gene and was expressed exclusively in the luteal phase in our microarray study. Therefore, we further functionally characterized the protein product of TOB-1 in vitro. To our knowledge, no studies have yet been conducted on reactive oxygen species-regulated tumor suppressor interactions in accordance with the biphasic nature of progesterone. This work demonstrates that progesterone can produce reactive oxygen species in MCF-7 cells and that TOB-1 exerts a series of non-genomic interactions that regulate antiproliferative activity by modulating the antioxidant enzyme superoxide dismutase. Furthermore, this study implicates PTEN as an interacting partner for TOB-1, which may regulate the downstream expression of cell cycle control protein p27 via multiple downstream signaling pathways of progesterone through a progesterone receptor, purely in a time- and concentration-dependent manner. These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival.

The role of chemokine receptor 4 and its ligand stromal cell derived factor 1 in breast cancer.

Breast tumour cells express the chemokine receptor C-X-C chemokine receptor type 4 (CXCR4) and frequently metastasize to organs with an abundant source of CXCR4 ligand, stromal cell derived factor1 (SDF1). For this reason, CXCR4/SDF1 has garnered much interest as a target for therapeutic intervention. The present study is an attempt to correlate the CXCR4/SDF1 expression patterns with clinicopathological factors, patient survival, and its coexistence and response to 17-ß estradiol (E2) and 4-hydoxytamoxifen (4OHT) in breast cancer cells. Immunohistochemistry and Reverse Transcriptase-Polymerase Chain Reaction were performed to assess the protein and gene level expressions of CXCR4 and SDF1 in normal and tumour breast tissue. The effect of E2 and 4OHT on expression of CXCR4 and SDF1 in breast cancer cells were assessed using RT-PCR, Immunofluorescence microscopy and colocalization. The CXCR4 and SDF1 were over expressed and have a significant correlation with each other as well as with histological grade, tumour size and poor survival of patients. The study also showed a modulatory effect of E2 and 4OHT on the expression and colocalization of CXCR4/SDF1 in breast cancer cells. The correlation of CXCR4/SDF1 with other parameters and modulatory effect of E2 and 4OHT on the expression and colocalization of CXCR4/SDF1 in breast cancer cells are likely to open up new avenues for the successful management of this malignancy.

Drug-induced senescence generates chemoresistant stemlike cells with low reactive oxygen species.

Tumor recurrence after chemotherapy or radiation remains a major obstacle to successful cancer treatment. A subset of cancer cells, termed cancer stem cells, can elude conventional treatments and eventually regenerate a tumor that is more aggressive. Despite the large number of studies, molecular events that govern the emergence of aggressive therapy-resistant cells with stem cell properties after chemotherapy are poorly defined. The present study provides evidence for the rare escape of tumor cells from drug-induced cell death, after an intermediate stay in a non-cycling senescent stage followed by unstable multiplication characterized by spontaneous cell death. However, some cells appear to escape and generate stable colonies with an aggressive tumor stem cell-like phenotype. These cells displayed higher CD133 and Oct-4 expression. Notably, the drug-selected cells that contained low levels of reactive oxygen species (ROS) also showed an increase in antioxidant enzymes. Consistent with this in vitro experimental data, we observed lower levels of ROS in breast tumors obtained after neoadjuvant chemotherapy compared with samples that did not receive preoperative chemotherapy. These latter tissues also expressed enhanced levels of ROS defenses with enhanced expression of superoxide dismutase. Higher levels of Oct-4 and CD133 were also observed in tumors obtained after neoadjuvant chemotherapy. Further studies provided evidence for the stabilization of Nrf2 due to reduced 26 S proteasome activity and increased p21 association as the driving signaling event that contributes to the transition from a high ROS quiescent state to a low ROS proliferating stage in drug-induced tumor stem cell enrichment.

Clinical breast examination: preliminary results from a cluster randomized controlled trial in India.

A cluster randomized controlled trial was initiated in the Trivandrum district (Kerala, India) on January 1, 2006, to evaluate whether three rounds of triennial clinical breast examination (CBE) can reduce the incidence rate of advanced disease incidence and breast cancer mortality. A total of 275 clusters that included 115,652 healthy women, aged 30-69 years, were randomly allocated to intervention (CBE; 133 clusters; 55,844 women) or control (no screening; 142 clusters; 59,808 women) groups. Performance characteristics (sensitivity, specificity, false-positive rate, and positive predictive value) of CBE were evaluated. An intention-to-treat analysis was performed for comparison of incidence rates between the intervention and control groups. Preliminary results for incidence are based on follow-up until May 31, 2009, when the first round of screening was completed. Of the 50,366 women who underwent CBE, 30 breast cancers were detected among 2880 women with suspicious findings in CBE screening that warranted further investigations. Sensitivity, specificity, false-positive rate, and positive predictive value of CBE were 51.7% (95% confidence interval [CI] = 38.2% to 65.0%), 94.3% (95% CI = 94.1% to 94.5%), 5.7% (95% CI = 5.5% to 5.9%), and 1.0% (95% CI = 0.7% to 1.5%), respectively. The age-standardized incidence rates for early-stage (stage IIA or lower) breast cancer were 18.8 and 8.1 per 100,000 women and for advanced-stage (stage IIB or higher) breast cancer were 19.6 and 21.7 per 100,000 women, in the intervention and control groups, respectively.