Breast density knowledge and willingness to delay treatment for pre-operative breast cancer imaging among women with a personal history of breast cancer.

BACKGROUND: Following a breast cancer diagnosis, it is uncertain whether women's breast density knowledge influences their willingness to undergo pre-operative imaging to detect additional cancer in their breasts. We evaluated women's breast density knowledge and their willingness to delay treatment for pre-operative testing. METHODS: We surveyed women identified in the Breast Cancer Surveillance Consortium aged ≥ 18 years, with first breast cancer diagnosed within the prior 6-18 months, who had at least one breast density measurement within the 5 years prior to their diagnosis. We assessed women's breast density knowledge and correlates of willingness to delay treatment for 6 or more weeks for pre-operative imaging via logistic regression. RESULTS: Survey participation was 28.3% (969/3,430). Seventy-two percent (469/647) of women with dense and 11% (34/322) with non-dense breasts correctly knew their density (p < 0.001); 69% (665/969) of all women knew dense breasts make it harder to detect cancers on a mammogram; and 29% (285/969) were willing to delay treatment ≥ 6 weeks to undergo pre-operative imaging. Willingness to delay treatment did not differ by self-reported density (OR:0.99 for non-dense vs. dense; 95%CI: 0.50-1.96). Treatment with chemotherapy was associated with less willingness to delay treatment (OR:0.67; 95%CI: 0.46-0.96). Having previously delayed breast cancer treatment more than 3 months was associated with an increased willingness to delay treatment for pre-operative imaging (OR:2.18; 95%CI: 1.26-3.77). CONCLUSIONS: Understanding of personal breast density was not associated with willingness to delay treatment 6 or more weeks for pre-operative imaging, but aspects of a woman's treatment experience were. CLINICALTRIALS: GOV : NCT02980848 registered December 2, 2016.

Application of an ultrasonic bone knife combined with a dental electric motor in the extraction of mandibular middle and low impacted teeth.

OBJECTIVE: To investigate the clinical application of an ultrasonic bone knife (UBK) combined with a dental electric motor (DEM) in the extraction of mandibular middle and low impacted teeth. METHODS: From January 2022 to May 2023,200 patients with wisdom teeth were randomly divided into three groups: experimental group A (UBK combined with DEM), experimental group B (UBK combined with high-speed turbine mobile phone (HSTMP)), and the control group (bone chisel split crown (BCSC)). The operation time, psychological state during operation, pain, swelling, limitation of mouth opening and other complications on the first, second and third days after operation were recorded. RESULTS: The operation time of experimental group A (EAG) (12.95 ± 2.12) minutes was shorter than that of experimental group B (EBG) (17.06 ± 2.25) minutes and the control group (CG) (23.43 ± 2.18) minutes, and the difference was statistically significant (P < 0.05). The psychological state of the EAG was significantly lower than that of the EBG and CG (P < 0.05). The postoperative pain, swelling, limitation of mouth opening and complications in the EAG were significantly lower than those in the EBG and CG (P < 0.05). CONCLUSION: UBK combined with DEM in the extraction of mandibular middle and low obstructed teeth has good results, good prognosis, high safety, short operation time, better psychological status of patients, low postoperative pain, swelling, mouth opening restriction and complication rate, and is currently the preferred extraction method.

The Orphan GPR50 Receptor Regulates the Aggressiveness of Breast Cancer Stem-like Cells via Targeting the NF-kB Signaling Pathway.

The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and online platform (UALCAN, GEPIA, and R2 gene analysis). The role of GPR50 in driving CSLC, sphere formation, cell proliferation, and migration was performed using shGPR50 gene knockdown, and the role of GPR50-regulated signaling pathways was examined by Western blotting and Luciferase Assay. Herein, we confirmed that the expression of G protein-coupled receptor 50 (GPR50) in cancer stem-like cells (CSLC) is higher than that in other cancer cells. We examined that the knockdown of GPR50 in CSLC led to decreased cancer properties, such as sphere formation, cell proliferation, migration, and stemness. GPR50 silencing downregulates NF-kB signaling, which is involved in sphere formation and aggressiveness of CSLC. In addition, we demonstrated that GPR50 also regulates ADAM-17 activity by activating NOTCH signaling pathways through the AKT/SP1 axis in CSLC. Overall, we demonstrated a novel GPR50-mediated regulation of the NF-κB-Notch signaling pathway, which can provide insights into CSLC progression and prognosis, and NF-κB-NOTCH-based CSLC treatment strategies.

Estrogen Receptor ß4 Regulates Chemotherapy Resistance and Induces Cancer Stem Cells in Triple Negative Breast Cancer.

Triple Negative Breast Cancer (TNBC) has the worst prognosis among all breast cancers, and survival in patients with recurrence is rarely beyond 12 months due to acquired resistance to chemotherapy, which is the standard of care for these patients. Our hypothesis is that Estrogen Receptor ß1 (ERß1) increases response to chemotherapy but is opposed by ERß4, which it preferentially dimerizes with. The role of ERß1 and ERß4 in influencing chemotherapy sensitivity has never been studied before. CRISPR/CAS9 was used to truncate ERß1 Ligand Binding Domain (LBD) and knock down the exon unique to ERß4. We show that the truncated ERß1 LBD in a variety of mutant p53 TNBC cell lines, where ERß1 ligand dependent function was inactivated, had increased resistance to Paclitaxel, whereas the ERß4 knockdown cell line was sensitized to Paclitaxel. We further show that ERß1 LBD truncation, as well as treatment with ERß1 antagonist 2-phenyl-3-(4-hydroxyphenyl)-5,7-bis(trifluoromethyl)-pyrazolo[1,5-a] pyrimidine (PHTPP), leads to increase in the drug efflux transporters. Hypoxia Inducible Factors (HIFs) activate factors involved in pluripotency and regulate the stem cell phenotype, both in normal and cancer cells. Here we show that the ERß1 and ERß4 regulate these stem cell markers like SOX2, OCT4, and Nanog in an opposing manner; and we further show that this regulation is mediated by HIFs. We show the increase of cancer cell stemness due to ERß1 LBD truncation is attenuated when HIF1/2α is knocked down by siRNA. Finally, we show an increase in the breast cancer stem cell population due to ERß1 antagonist using both ALDEFLUORTM and SOX2/OCT4 response element (SORE6) reporters in SUM159 and MDA-MB-231 cell lines. Since most TNBC cancers are ERß4 positive, while only a small proportion of TNBC patients are ERß1 positive, we believe that simultaneous activation of ERß1 with agonists and inactivation of ERß4, in combination with paclitaxel, can be more efficacious and yield better outcome for chemotherapy resistant TNBC patients.

Breast cancer incidence among women with a family history of breast cancer by relative's age at diagnosis.

BACKGROUND: Women with a first-degree family history of breast cancer are often advised to begin screening when they are 10 years younger than the age at which their relative was diagnosed. Evidence is lacking to determine how much earlier they should begin. METHODS: Using Breast Cancer Surveillance Consortium data on screening mammograms from 1996 to 2016, the authors constructed a cohort of 306,147 women 30-59 years of age with information on first-degree family history of breast cancer and relative's age at diagnosis. The authors compared cumulative 5-year breast cancer incidence among women with and without a first-degree family history of breast by relative's age at diagnosis and by screening age. RESULTS: Among 306,147 women included in the study, approximately 11% reported a first-degree family history of breast cancer with 3885 breast cancer cases identified. Women reporting a relative diagnosed between 40 and 49 years and undergoing screening between ages 30 and 39 or 40 and 49 had similar 5-year cumulative incidences of breast cancer (respectively, 18.6/1000; 95% confidence interval [CI], 12.1, 25.7; 18.4/1000; 95% CI, 13.7, 23.5) as women without a family history undergoing screening between 50-59 years of age (18.0/1000; 95% CI, 17.0, 19.1). For relative's diagnosis age from 35 to 45 years of age, initiating screening 5-8 years before diagnosis age resulted in a 5-year cumulative incidence of breast cancer of 15.2/1000, that of an average 50-year-old woman. CONCLUSION: Women with a relative diagnosed at or before age 45 may wish to consider, in consultation with their provider, initiating screening 5-8 years earlier than their relative's diagnosis age.

Secretory phospholipase sPLA2-IIAloss impairs tumorigenic and metastatic potential in breast cancer cells.

Breast cancer stem cells (BCSCs) are slow cycling cells that escape the traditional chemo-radio-therapy, thereby contributing in resistance and recurrence. Although several markers have been identified, it is still challenging to develop strategies targeting them. In this study, we have isolated BCSCs from MCF-7 cell line using markers CD44+/CD24-/low, which showed higher percentage of mammospheres in CSC population. Moreover, in vivo tumorigenic potential of BCSCs showed as low as 10,000 cells had the ability to develop tumors when transplanted into NOD-SCID mice. We observed an increased level of EMT markers in CSC population. Overexpression of secretory phospholipase sPLA2-IIA was found in CSCs. Further, we have uncovered the upregulation of sPLA2-IIA mediated through JNK signaling in breast cancer cells whereas knockdown of sPLA2-IIA reduces JNK signaling, cell proliferation, EMT and in vivo tumorigenic potential in breast cancer cells. Our study reveals overexpression of sPLA2-IIA in two different breast cancer cells such as MCF7 (ER+,PR+) and a triple negative, MDA-MB-231 (ER-PR-HER2-). Further, the novel role of sPLA2-IIA was discerned by unraveling the molecular mechanism, which regulates the cell proliferation and metastasis in breast cancer cells.

CBCRisk-Black: a personalized contralateral breast cancer risk prediction model for black women.

PURPOSE: Black breast cancer (BC) survivors have a higher risk of developing contralateral breast cancer (CBC) than Whites. Existing CBC risk prediction tools are developed based on mostly White women. To address this racial disparity, it is crucial to develop tools tailored for Black women to help them inform about their actual risk of CBC. METHODS: We propose an absolute risk prediction model, CBCRisk-Black, specifically for Black BC patients. It uses data on Black women from two sources: Breast Cancer Surveillance Consortium (BCSC) and Surveillance, Epidemiology, and End Results (SEER). First, a matched lasso logistic regression model for estimating relative risks (RR) is developed. Then, it is combined with relevant hazard rates and attributable risks to obtain absolute risks. Six-fold cross-validation is used to internally validate CBCRisk-Black. We also compare CBCRisk-Black with CBCRisk, an existing CBC risk prediction model. RESULTS: The RR model uses data from BCSC on 744 Black women (186 cases). CBCRisk-Black has four risk factors (RR compared to baseline): breast density (2.13 for heterogeneous/extremely dense), family history of BC (2.28 for yes), first BC tumor size (2.14 for T3/T4, 1.56 for TIS), and age at first diagnosis of BC (1.41 for < 40). The area under the receiver operating characteristic curve (AUC) for 3- and 5-year predictions are 0.72 and 0.65 for CBCRisk-Black while those are 0.65 and 0.60 for CBCRisk. CONCLUSION: CBCRisk-Black may serve as a useful tool to clinicians in counseling Black BC patients by providing a more accurate and personalized CBC risk estimate.

Decision quality and regret with treatment decisions in women with breast cancer: Pre-operative breast MRI and breast density.

PURPOSE: We evaluated self-report of decision quality and regret with breast cancer surgical treatment by pre-operative breast MRI use in women recently diagnosed with breast cancer. METHODS: We conducted a survey with 957 women aged 18 + with stage 0-III breast cancer identified in the Breast Cancer Surveillance Consortium. Participants self-reported receipt of pre-operative breast MRI. Primary outcomes were process measures in the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI) (continuous outcome) and Decision Regret Scale (dichotomized outcome as any/none). Generalized estimating equations with linear and logit link were used to estimate adjusted associations between breast MRI and primary outcomes. All analyses were also stratified by breast density. RESULTS: Survey participation rate was 27.9% (957/3430). Study population was primarily > 60 years, White, college educated, and diagnosed with early-stage breast cancer. Pre-operative breast MRI was reported in 46% of women. A higher proportion of women who were younger age (< 50 years), commercially insured, and self-detected their breast cancer reported pre-operative breast MRI use. In adjusted analysis, pre-operative breast MRI use compared with no use was associated with a small but statistically significantly higher decision quality scores (69.5 vs 64.7, p-value = 0.043). Decision regret did not significantly differ in women who reported pre-operative breast MRI use compared with no use (54.2% v. 48.7%, respectively, p-value = 0.11). Study results did not vary when stratified by breast density for either primary outcome. CONCLUSIONS AND RELEVANCE: Breast MRI use in the diagnostic work-up of breast cancer does not negatively alter women's perceptions of surgical treatment decisions in early survivorship. CLINICAL TRIALS REGISTRATION NUMBER: NCT03029286.

Accuracy of the Breast Cancer Surveillance Consortium Model Among Women with LCIS.

PURPOSE: The Breast Cancer Surveillance Consortium (BCSC) model predicts risk of invasive breast cancer risk based on age, race, family history, breast density, and history of benign breast disease, including lobular carcinoma in situ (LCIS). However, validation studies for this model included few women with LCIS. We sought to evaluate the accuracy of the BCSC model among this cohort. METHODS: Women with LCIS diagnosed between 1983 and 2017 were identified from a prospectively maintained database. The BCSC score was calculated; those with prior breast cancer, unknown breast density, age < 35 years or > 74 years, or with history of chemoprevention use were excluded. The Kaplan-Meier method was used to estimate incidence rates. Time-dependent receiver operating characteristic (ROC) analysis was used to analyze the discriminative capacity of the model. RESULTS: 1302 women with LCIS were included. At a median follow-up of 7 years, 152 women (12%) developed invasive cancer (6 with bilateral disease). Cumulative incidences of invasive breast cancer were 7.1% (95% CI 5.6-8.7) and 13.3% (95% CI 10.9-15.6), respectively, and the median BCSC risk scores were 4.9 and 10.4, respectively, at 5 and 10 years. The median 10-year BCSC score was significantly lower than the 10-year Tyrer-Cuzick score (10.4 vs 20.8, p < 0.001). The ROC curve scores (AUC) for BCSC at 5 and 10 years were 0.59 (95% CI 0.52-0.66) and 0.58 (95% CI 0.52-0.64), respectively. CONCLUSION: The BCSC model has moderate accuracy in predicting invasive breast cancer risk among women with LCIS with fair discrimination for risk prediction between individuals.

Age at initiation of screening mammography by family history of breast cancer in the breast cancer surveillance consortium.

PURPOSE: Women with a first-degree family history of breast cancer (FHBC) are sometimes advised to initiate screening mammography when they are 10 years younger than the age at which their youngest relative was diagnosed, despite a lack of unambiguous evidence that this is an effective strategy. It is unknown how often this results in women initiating screening earlier (< 40 years) than screening guidelines recommend for average-risk women. METHODS: We examined screening initiation age by FHBC and age at diagnosis of the youngest relative using data collected by the Breast Cancer Surveillance Consortium on 74,838 first screening mammograms performed between 1996 and 2016. RESULTS: Of the 74,838 women included in the study, nearly 9% reported a FHBC. Approximately 16.8% of women who initiated mammography before 40 years reported a FHBC. More women with a FHBC than without initiated screening < 40 years (48% vs. 23%, respectively). Among women with a FHBC who initiated screening < 40 years, 65% were 10 years younger than the age at which their relative was diagnosed. CONCLUSION: Women with a first-degree relative diagnosed with breast cancer were more likely to start screening before 40 years than women reporting no FHBC, especially if their relative was diagnosed before 50 years.

MicroRNA regulation of cancer stem cells in the pathogenesis of breast cancer.

Breast cancer is the most common cancer among women and accounts for 30% of all female malignancies worldwide. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that exhibit multiple characteristics including differentiation capacity, self-renewal and therapeutic resistance. Recently, BCSCs have attracted attention due to their modulation of breast tumor behaviors and drug resistance. miRNAs are small noncoding mRNAs involved in virtually all biological processes, including stem cell development, maintenance and differentiation. In breast cancer, miRNAs appear to be multi-faceted since they can act as either suppressors or oncogenes to regulate breast cancer progression. This review summarizes the critical roles of miRNAs in regulating multiple signaling pathways such as Wnt/ß-catenin, Notch, PI3K/AKT/mTOR, BMI-1 and STAT3 that are important for the BCSC maintenance.

UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1.

Uncoupling protein 1 (UCP1) has been implicated in ameliorating metabolic related disorders, of which most symptoms are risk factors for breast cancer. Here, we found that UCP1 was obviously downregulated in basal-like breast cancer (BLBC) and was positively correlated with improved survival. However, the underlying regulatory mechanisms remain largely unknown. Our studies showed that UCP1 inhibited tumor progression via suppressing aldehyde dehydrogenase (ALDH)-positive breast cancer stem cell (BCSC) population in BLBC. Furthermore, we found that UCP1 induced the upregulation of fructose bisphosphatase 1 (FBP1) which was previously blocked by Snail overexpression, and UCP1 decreased ALDH-positive BCSCs via FBP1-dependent metabolic rewiring, which could be reversed by Snail overexpression. In addition, breast cancer cells co-cultured with UCP1-deficient adipocytes had increased proportion of ALDH-positive BCSCs, indicating a potential protection role of UCP1 in tumor microenvironment. These results suggested that UCP1 suppressed BCSCs through inhibiting Snail-mediated repression of FBP1, and that upregulation of UCP1 might be a previously undescribed therapeutic strategy for combating breast cancer. Graphical abstract.

Theranostics for Breast Cancer Stem Cells.

Effectively targeting and treating breast cancer stem cells (BCSCs), which have been linked to tumor development and metastasis, and recurrence still remains a challenging issue in preclinic and clinic. Screening and identifying characteristic BCSC biomarkers is important for distinguishing BCSCs from differentiated tumor cells within the tumor mass. Molecular imaging and nanotechnology are evolving as new fields that have a potentially high research and clinical impact. Developing the biocompatible contrast agents conjugated with high-affinity biomarker to selectively target BCSCs and is one of the key prerequisites for image-guided diagnosis and monitoring therapy of BCSCs. Very recently, we documented the extra domain-B fibronectin (EDB-FN), which is considered as a new putative biomarker for BCSCs (NDY-1 cell) derived from human breast carcinosarcoma. We here review BCSC-targeted theranostics in vitro and in vivo by delivering siRNA or drug using the nanoparticles conjugated with a small peptide specific to EDB-FN.

MicroRNAs and breast cancer stem cells: Potential role in breast cancer therapy.

MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future.

Airborne metals and polycyclic aromatic hydrocarbons in relation to mammographic breast density.

BACKGROUND: Breast density is strongly related to breast cancer. Identifying associations between environmental exposures and density may elucidate relationships with breast cancer. Metals and polycyclic aromatic hydrocarbons (PAHs) may influence breast density via oxidative stress or endocrine disruption. METHODS: Study participants (n = 222,581) underwent a screening mammogram in 2011 at a radiology facility in the Breast Cancer Surveillance Consortium. Zip code residential levels of airborne PAHs and metals (arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium) were assessed using the 2011 EPA National Air Toxics Assessment. Breast density was measured using the Breast Imaging-Reporting and Data System (BI-RADS) lexicon. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI) for the individual air toxics and dense breasts (BI-RADS 3 or 4). Weighted quantile sum (WQS) regression was used to model the association between the air toxic mixture and density. RESULTS: Higher residential levels of arsenic, cobalt, lead, manganese, nickel, or PAHs were individually associated with breast density. Comparing the highest to the lowest quartile, higher odds of having dense breasts were observed for cobalt (OR = 1.60, 95% CI 1.56-1.64) and lead (OR = 1.56, 95% CI 1.52-1.64). Associations were stronger for premenopausal women. The WQS index was associated with density overall (OR = 1.22, 95% CI 1.20-1.24); the most heavily weighted air toxics were lead and cobalt. CONCLUSIONS: In this first study to evaluate the association between air toxics and breast density, women living in areas with higher concentrations of lead and cobalt were more likely to have dense breasts.

Mahanine, A dietary phytochemical, represses mammary tumor burden in rat and inhibits subtype regardless breast cancer progression through suppressing self-renewal of breast cancer stem cells.

Mahanine (MH), a carbazole alkaloid isolated from an edible plant (Murraya koenigii), potentially inhibits the growth of altered subtypes of breast cancer cells in vitro and significantly reduced the mammary tumor burden in N-Methyl-N-nitrosourea (MNU) induced rat. The experimental results showed that 20-25 µM of MH for 24 h of treatment was very potent to reduce the cell proliferation through apoptosis with arresting the cells in G0/G1 in both ER+/p53WT MCF-7 and triple negative/p53Mut MDA-MB-231 cells. On the other hand, 10-15 µM of MH exposure to those two cell lines, caused inhibition of mammosphere formation and reduction of CD44high/CD24low/epithelial-specific antigen-positive (ESA+) population, which ultimately led to loss of self-renewal ability of breast cancer stem cells. Further, in vivo observation indicated that intraperitoneal injection of MH for four weeks with a dose of 50 mg/kg body weight thrice in a week, significantly (P =  0.03) reduced the mammary tumor weight in MNU induced rat. In conclusion, this study provides the novel insight into the mechanism of MH mediated growth arrest in subtype irrespective breast cancer progression.

Up-modulation of PLC-ß2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+ phenotype: a promising target for preventing progression of TNBC.

BACKGROUND: The malignant potential of triple negative breast cancer (TNBC) is also dependent on a sub-population of cells with a stem-like phenotype. Among the cancer stem cell markers, CD133 and EpCAM strongly correlate with breast tumor aggressiveness, suggesting that simultaneous targeting of the two surface antigens may be beneficial in treatment of TNBC. Since in TNBC-derived cells we demonstrated that PLC-ß2 induces the conversion of CD133high to CD133low cells, here we explored its possible role in down-modulating the expression of both CD133 and EpCAM and, ultimately, in reducing the number of TNBC cells with a stem-like phenotype. METHODS: A magnetic step-by-step cell isolation with antibodies directed against CD133 and/or EpCAM was performed on the TNBC-derived MDA-MB-231 cell line. In the same cell model, PLC-ß2 was over-expressed or down-modulated and cell proliferation and invasion capability were evaluated by Real-time cell assays. The surface expression of CD133, EpCAM and CD44 in the different experimental conditions were measured by multi-color flow cytometry immunophenotyping. RESULTS: A CD133+/EpCAM+ sub-population with high proliferation rate and invasion capability is present in the MDA-MB-231 cell line. Over-expression of PLC-ß2 in CD133+/EpCAM+ cells reduced the surface expression of both CD133 and EpCAM, as well as proliferation and invasion capability of this cellular subset. On the other hand, the up-modulation of PLC-ß2 in the whole MDA-MB-231 cell population reduced the number of cells with a CD44+/CD133+/EpCAM+ stem-like phenotype. CONCLUSIONS: Since selective targeting of the cells with the highest aggressive potential may have a great clinical importance for TNBC, the up-modulation of PLC-ß2, reducing the number of cells with a stem-like phenotype, may be a promising goal for novel therapies aimed to prevent the progression of aggressive breast tumors.

Criteria for identifying radiologists with acceptable screening mammography interpretive performance on basis of multiple performance measures.

OBJECTIVE: Using a combination of performance measures, we updated previously proposed criteria for identifying physicians whose performance interpreting screening mammography may indicate suboptimal interpretation skills. MATERIALS AND METHODS: In this study, six expert breast imagers used a method based on the Angoff approach to update criteria for acceptable mammography performance on the basis of two sets of combined performance measures: set 1, sensitivity and specificity for facilities with complete capture of false-negative cancers; and set 2, cancer detection rate (CDR), recall rate, and positive predictive value of a recall (PPV1) for facilities that cannot capture false-negative cancers but have reliable cancer follow-up information for positive mammography results. Decisions were informed by normative data from the Breast Cancer Surveillance Consortium (BCSC). RESULTS: Updated combined ranges for acceptable sensitivity and specificity of screening mammography are sensitivity≥80% and specificity≥85% or sensitivity 75-79% and specificity 88-97%. Updated ranges for CDR, recall rate, and PPV1 are: CDR≥6 per 1000, recall rate 3-20%, and any PPV1; CDR 4-6 per 1000, recall rate 3-15%, and PPV1≥3%; or CDR 2.5-4.0 per 1000, recall rate 5-12%, and PPV1 3-8%. Using the original criteria, 51% of BCSC radiologists had acceptable sensitivity and specificity; 40% had acceptable CDR, recall rate, and PPV1. Using the combined criteria, 69% had acceptable sensitivity and specificity and 62% had acceptable CDR, recall rate, and PPV1. CONCLUSION: The combined criteria improve previous criteria by considering the interrelationships of multiple performance measures and broaden the acceptable performance ranges compared with previous criteria based on individual measures.

Association of BCSC-1 with human esophageal squamous cell carcinoma.

Breast cancer suppressor candidate-1 (BCSC-1) is a newly identified candidate tumor suppressor gene. BCSC-1 shows decreased levels in a variety of cancer types. In this study, we investigated the association between BCSC-1 and human esophageal squamous cell carcinoma (ESCC). BCSC-1 expression was detected in ESCC and normal tissues adjacent to tumor tissues by Western blot analysis and real-time PCR  as well as immunohistochemistry of paraffin sections. The relationships between BCSC-1 expression and various clinicopathological characteristics were analyzed. Western blot analysis and real-time PCR showed that levels of BCSC-1 protein and mRNA expression in ESCC significantly decreased compared with those in adjacent normal tissues.  Immunohistochemistry exhibited marked reduction of BCSC-1 in 38 of 105 ESCC specimens. Moreover, downregulation of BCSC-1 was associated with the grade of tumor cellular differentiation (P<0.05). These findings indicate that BCSC-1 downregulation in ESCC is associated with carcinogenesis and may play important roles during the process of ESCC cancer development.

Breast cancer stem cells, EMT and therapeutic targets.

A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo "epithelial to mesenchymal transition" (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-ß, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.