Family physician (FP) knowledge regarding breast cancer risk assessment and prevention strategies such as chemoprevention are important in ensuring that women at high risk for breast cancer are identified and receive proper preventive care. There are many factors which can moderately increase a woman’s risk of developing breast cancer, such as short-term hormone replacement therapy use and being nulliparous over the age of 30 years. Some factors increase a woman’s risk to such an extent that she is deemed “high risk” for breast cancer development, including having a family history of breast cancer or having a personal history of atypical benign breast disease. We conducted a cross-sectional survey of a stratified random sample of 2500 family physicians selected from across Canada to examine breast cancer risk assessment knowledge and practices, chemoprevention knowledge and prescribing practices, attitudes towards breast cancer chemoprevention, and barriers towards its utilization in Canadian FPs. We found that while the majority of physicians identified a woman with a family history of breast cancer (97%) as being high risk, a large proportion of physicians (40%) underestimated the risk associated with having a personal history of atypical benign breast disease. Physicians also tended to overestimate the risk associated with hormone replacement therapy use (70%) and the risk associated with nulliparity over the age of 30 years (50%). We also found that less than 15% of our sample had knowledge about chemoprevention and less than 7% had ever prescribed breast cancer chemoprevention (i.e. tamoxoifen or raloxifene) for primary prevention. Possible predictors of both knowledge of risk assessment and chemoprevention and prescription of chemoprevention were examined. Using multiple logistic regression, we found that several variables significantly predicted physician knowledge of these risk factors and prescription practices including patient load, medical experience and sex. The results of this study indicate that family physicians may need to become more aware about breast cancer prevention methods and risk factors for breast cancer, and in particular those that place a woman at high risk for breast cancer development. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2009-09-19 13:11:22.899

Evidence indicates that the mammary epithelium is arranged in a hierarchy in which mature luminal and myoepithelial cells are derived from stem cells through a series of lineage-restricted intermediates. One of the more compelling hypotheses in breast cancer research is that transformation of a particular cell within the hierarchy will initiate a tumour with a specific molecular profile and clinical outcome. If this is true, valuable insight into tumourigenesis can be gained by investigating normal and malignant pathways of differentiation. A well-known tumour suppressor in breast cancer, BRCA1, plays a role in mammary epithelial differentiation. It has been proposed that haploinsufficiency or loss of BRCA1, either by germline mutation or sporadic downregulation, blocks differentiation producing a pool of genetically unstable mammary stem/progenitor cells that are prime targets for transformation. Thus, investigation of BRCA1 regulation and its role in differentiation are important to our understanding of breast cancer etiology. In this study, we determined that BRCA1 is at the end of a transcriptional network comprised of NRF-1 and GABP, a transcription factor comprised of two distinct subunits GABPalpha and GABPbeta. Decreased BRCA1 transcription in SK-BR-3 cells was found to be caused by aberrant activation of the GABPbeta promoter by an NRF-1 binding protein complex. We determined that the SWI/SNF family members BRG1, ARID1A and BAF155 may participate in the complex that activates GABPbeta transcription in conjunction with NRF-1. Examination of NRF-1, GABP and BRCA1 in 3D culture models suggests that mammary epithelial differentiation is biphasic with the transition between the phases being driven by changes in BRCA1 expression and localization. In the first phase, BRCA1 promotes differentiation in the nucleus, and in the second phase, BRCA1 is downregulated as a result of diminished GABP expression and relocated to an apical position, presumably to facilitate cell polarization. Following BRCA1 downregulation, NRF-1 and GABP levels increase indicating they are inducing oxidative phosphorylation in the second phase of differentiation. The involvement of NRF-1 and GABP in cellular respiration as well as differentiation through targets such as BRCA1 suggests that these proteins may integrate the cellular functions and mitochondrial metabolism required for mammary epithelial differentiation. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2012-09-11 14:22:26.407

Aldehyde dehydrogenases (ALDHs) have been used as stem cell markers in a variety of tissues, including the breast. However, it is currently unknown whether ALDH family members participate in normal mammary development or breast cancer. In this study, we set out to elucidate a role for one such protein, ALDH1A3, in mammary luminal cell differentiation and tumorigenesis. We have identified three ALDH1A3 splice variants in breast cell lines, raising the question of whether alternative splicing contributes to cancer development by altering ALDH1A3 activity. We also observed impaired cell motility and defective differentiation in normal breast cell lines cultured in the presence of diethylaminobenzaldehyde (DEAB), a general inhibitor of ALDH activity, suggesting that certain ALDH family members are important for these processes. Based on preliminary in vitro experiments monitoring morphology of breast cell line acini formation and differentiation, doxycyclin-inducible lentiviral TRIPZ-shALDH1A3 pools did not show any obvious defects in differentiation. In addition to this finding, ALDH1A3 mRNA expression levels in primary breast tumour samples (n=39) did not significantly correlate with age, histological grade or hormone receptor status (p-value>0.05). Overall, the results of this study suggest that while ALDH1A3 itself may not be directly involved in breast morphogenesis or cancer formation, other ALDH family members function to facilitate differentiation and cell motility, processes which are important both for normal mammary gland development as well as cancer progression and metastasis. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2012-09-26 13:59:08.166

No description available.

Normal breast growth and development depends on functional androgen:estrogen (A:E) balance. Androgen actions are mediated by the androgen receptor (AR), a DNA-binding, transcriptional-regulatory protein. Decreased AR transactivational. activity lowers A:E balance and may result in functional hyperestrogenicity: this could promote the pathogenesis of breast cancer (BC). The present study is the first to seek AR mutations in female BC. The length of the polymorphic CAG-repeat in exon 1 of the AR correlates inversely with the transactivational activity of the AR. Using 10% polyacrylamide gels, I found a significant (p < 0.0001) shift to greater CAG-repeat lengths in BC samples. This suggests a role for ARs with long polyglutamine tracts in the initiation and/or progression of BC. Exons 2--8 of the AR in 81 fresh frozen BC tumor tissues were screened for mutations using SSCP analysis. I did not detect any mutations in these exons.

This research is a follow up of a "Breast Week" which was organized in Freetown, Sierra Leone. The specific objective of this study was to assess the effectiveness of the knowledge and teachings given to the women who participated in this project. The unrecorded cases of breast lumps and breast cancer observed in women in Sierra Leone prompted the researcher to undertake this present study. A quantitative approach was adopted and a structured interview schedule and an observational checklist guided the data collection process. A sample size of 120 women (10%) who participated in the "breast week" was obtained through systematic sampling. The first part of the study involved assessment of the theoretical background of the research topic followed by the second phase during which the women demonstrated Breast Self-Examination to detect abnormalities of the breasts. Discussions and analysis of the findings are presented in three sections. Texts from open ended questions were categorized and explained in numerical terms as the study was quantitative in nature. The data was processed through use of SPSS and Microsoft Excel. Frequency counts were applied to the data, use of non-parametric tests on the number of women who practiced Breast Self-Examination before and after the breast week showed a statistically significant difference in the number of women now practicing BSE as a screening method for breast cancer after receiving the health education. It was found that the majority of the women linked breast cancer to the signs and symptoms associated with it and were able to describe the disease as one that kills women if not promptly detected and/or treated appropriately. Findings indicate that the majority of the women (78.3%) had previously had mmor breast problems. An assessment of the effectiveness of knowledge on breast cancer showed that these women could identify breast cancer as a disease that affects women and may cause deaths if not detected on time or treated promptly. These women were able to demonstrate to the researcher how they examine their breasts to exclude abnormalities. Three women had breast lumps detected through examination of the breasts during the breast week. Two of them had had the lumps removed and are currently on medication. One of the women who had a breast lump detected was financially constrained and could not afford the cost of surgery. The number of women who can now perform BSE increased (95.0%) after having the knowledge on breast cancer and BSE. The majority of the women (97.4%) received information on how to examine their breasts for breast cancer through the information provided during the breast week. It is thus concluded that the objectives of the breast week were met. / Thesis (M.N.)-University of Natal, Durban, 2004.

Since 1942, when Bittner reported the incidence of non-induced tumors occuring in mice, strains of laboratory mice producing mammary carcinomas have been used as tools in research. Although not ideal for human studies, the histological and morophological similarities of the human and mouse mammary glands make it an excellent model to study the development of breast cancer. This study was performed to develop a rapid and consistent classification system for mouse mammary tissue, and compare various tumors to this system.Laboratory mice from the A and Balb/c strains were utilized in these studies. The three types of tumors developed in these mice were, non-induced, induced, and transplanted. Specimens of these tumors were collected and studied via light and electron microscopy for cellularchanges of tumor cells. These tumors were then classified according to the new system. These various tumors ranged from Class 0, which were normal cells, through gradual cellular changes to a Class IV, which were totally undifferentiated cells. host induced and non-induced tumors were Class III or IV, while the transplanted tumors were Class IV. This system facilitated the classification of mouse mammary tumors.

In this study, the mRNA and protein levels of hypoxia inducible factor 1 (HIF-1α), and a number of genes regulated by hypoxia (VEGF, GLUT-1, p53), were determined in four breast carcinoma cell lines, peripheral blood mononuclear cells (PBMCs) of patients with breast cancer and Type 1 diabetes (TIDM), and in human breast and brain tumour tissue. Breast carcinoma cells and PMBCs from both patients and normal controls were exposed to hypoxia (≤1% 0 2) and/or high glucose. Both up-regulated and down-regulated HIF-1α, GLUT-1 and p53 mRNA expression was observed in the breast carcinoma cell lines exposed to hypoxia and/or high glucose, and in controls for osmolarity, confirming that hypoxic regulation of HIF-1α, p53 and possibly GLUT-1 occurs post-transcriptionally. Conversely, up-regulation of HIF- 1α and GLUT-1 mRNA was observed in patients with TIDM exposed to high glucose. The GLUT-1 mRNA up-regulation observed in patients without complications differed significantly from normal controls, where up to a 2 fold increase in expression was observed over that of patients with complications. This may indicate that the expression and function of glucose transporters differs in these patients, potentially leading to fewer complications. Investigation of breast and glial cell tumour tissue demonstrated that both HIF-1α and GLUT- 1 mRNA expression levels increase with disease progression, indicating that up-regulation of HIF-1α is partly at the transcriptional level (Søndergaard et al, 2002). Follow-up survival studies in all patients with glial cell tumours showed that HIF-1α protein expression is a significant prognostic factor in cumulative overall survival. An additional investigation of p53 or p73 polymorphisms in the development of carcinoma of the breast did not find that they were significant risk factors in the development of the disease in the British Caucasoid population. Further studies are required using larger sample populations investigating HIF-1α protein to determine the precise role of HIF-1 in the response to hypoxia and angiogenesis in disease in man.

No description available.

No description available.