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The promoter of the interferon regulatory factor-1 (IRF-1) gene contains at position -47 to -38 an evolutionary conserved binding sequence for the inducible transcription factor NF-kappa B. This site is highly homologous to a transcriptionally active site from the MHC class I enhancer. In this study, we show by in vitro assays using purified NF-kappa B that the kappa B motif in the IRF-1 promoter binds the factor specifically and with high affinity, comparable to various other cis-acting kappa B elements. Two copies of the IRF-1 kappa B site fused to the heterologous c-fos promoter conferred induction of a chloramphenicol acetyl transferase (CAT) reported gene in response to stimulation of L929 fibroblasts with various NF-kappa B inducers, such as tumor necrosis factor alpha (TNF alpha) or phorbol 12-myristate 13-acetate (PMA). Mutation of the binding site completely abolished transcriptional inducibility of the heterologous promoter. Surprisingly, the same IRF-1 kappa B motif in context of the homologous IRF-1 promoter was transcriptionally inactive in CAT assays. The very weak induction of the IRF-1 promoter in response to TNF treatment or infection of fibroblasts with Newcastle disease virus (NDV) was barely affected by point mutation of the kappa B site or loss of the site by truncation of the promoter. Analysis of the occupational state of the chromosomal IRF-1 kappa B site by in vivo foot-printing revealed that no footprint was induced over the kappa B motif in the IRF-1 promoter after PMA treatment of L929 fibroblast cells, despite the simultaneous induction of IRF-1 mRNA and NF-kappa B binding activity. Constitutive footprints were detected at a CCAAT and GC-rich region in the promoter. This is the first example of a high-affinity NF-kappa B binding site within a promoter which may not participate in transcriptional regulation under conditions activating NF-kappa B DNA binding and gene expression.

Purpose: To investigate person, cancer and treatment determinants of immediate breast reconstruction (IBR) in Australia. Methods: Bi-variable and multi-variable analyses of the Quality Audit database. Results: Of 12,707 invasive cancers treated by mastectomy circa 1998-2010, 8% had IBR. This proportion increased over time and reduced from 29% in women below 30 years to approximately 1% in those aged 70 years or more. Multiple regression indicated that other IBR predictors included: high socio-economic status; private health insurance; being asymptomatic; a metropolitan rather than inner regional treatment centre; higher surgeon case load; small tumour size; negative nodal status, positive progesterone receptor status; more cancer foci; multiple affected breast quadrants; synchronous bilateral cancer; not having neo-adjuvant chemotherapy, adjuvant radiotherapy or adjuvant hormone therapy; and receiving ovarian ablation. Conclusions: Variations in access to specialty services and other possible causes of variations in IBR rates need further investigation. Refereed/Peer-reviewed

We analyzed New South Wales Central Cancer Registry data for 1980-2003, to determine time trends in case fatality from ovarian cancer, after adjusting for stage, histological, and sociodemographic factors, and to consider service-delivery and research implications. After adjusting for covariates, the relative risk (95% confidence limit) of ovarian-cancer death reduced to 0.51 (0.46, 0.57) for 1999-2003 compared with 1980-1983. Relative risks were higher for adenocarcinomas and other specified and unspecified cancers than serous carcinomas, but lower for endometrioid carcinomas, sex cord-stromal and germ cell tumors. The probability of diagnosis with localized as opposed to more advanced disease was lower in older patients, the lowest socioeconomic stratum, women born in non-English-speaking countries, and more recent diagnostic periods. Approximately 61% of ovarian cancers had distant metastases at diagnosis in 1999-2003. Poorer survivals apply to older patients. Research directed at finding an effective screening test for epithelial ovarian cancer remains a priority.

Background: The optimal surgical treatment of early breast cancer in young women is not fully determined, while past reports indicate a trend to the increased use of breast-conserving surgery (BCS). This study aims to assess the trend in Australia and New Zealand of BCS use between 1999 and 2006 and to determine pathological factors associated with it. Methods: Data on cancer characteristics and surgical procedures in younger patients with early breast cancer reported to the National Breast Cancer Audit have been analysed. Results: There was little change in the rate of BCS over the last 7 years with an overall rate of 53%. The main factors associated with the use of BCS are low histological grade, absence of extensive intraductal carcinoma (EIC), negative lymph node involvement, unifocal tumour and small tumour size. Conclusion: Between 1999 and 2006, the use of BCS for early breast cancer treatment in younger women was stable. These results show that surgeons contributing data to the National Breast Cancer Audit appear to use pathological factors that are known to increase the risk of local recurrence after BCS, in selecting mastectomy for younger women.

This study investigated associations of degree of spread at diagnosis of breast cancer and socio-demographic factors with the risk of death among NSW females diagnosed in 1980-2003. Trends by diagnostic period, socio-demographic differences, and the implications for cancer control were considered. NSW Central Cancer Registry data were analyzed using regression and rank-order tests to show predictors of death from breast cancer and trends in degree of spread. Compared with localized disease, case fatality was thrice and 14 times higher for cancers with regional spread and distant metastases, respectively. After adjusting for degree of spread and socio-demographic differences, the relative risk of death from breast cancer has declined in recent diagnostic periods compared with the 1980-1983 baseline, reaching a low of 0.38 (0.35, 0.40) for 1999-2003. Age-specific analyses indicated that relative risks were lower in 1999-2003 for 50-69 year olds (RR = 0.31) than younger (RR = 0.40), or older (RR = 0.46) females. Regional or distant disease at diagnosis was lowest in the older age groups, the highest socio-economic stratum and in more recent periods. Females born in non-English speaking countries presented with more advanced disease, as did metropolitan women with the highest access to health services. Degree of spread of cancer at diagnosis is a powerful predictor of case fatality. Case fatalities from breast cancer have declined by diagnostic period, after adjusting for degree of spread, which may reflect treatment and screening advances. Attention should be directed at reducing disparities by socio-economic status and encouraging migrant women to present earlier.

To investigate patient, cancer and treatment characteristics in females with breast cancer from more remote areas of Australia, to better understand reasons for their poorer outcomes, bi-variable and multivariable analyses were undertaken using the National Breast Cancer Audit database of the Society of Breast Surgeons of Australia and New Zealand. Results indicated that patients from more remote areas were more likely to be of lower socioeconomic status and be treated in earlier diagnostic epochs and at inner regional and remote rather than major city centres. They were also more likely to be treated by low case load surgeons, although this finding was only of marginal statistical significance in multivariable analysis (p=0.074). Patients from more remote areas were less likely than those from major cities to be treated by breast conserving surgery, as opposed to mastectomy, and less likely to have adjuvant radiotherapy when having breast conserving surgery. They had a higher rate of adjuvant chemotherapy. Further monitoring will be important to determine whether breast conserving surgery and adjuvant radiotherapy utilization increase in rural patients following the introduction of regional cancer centres recently funded to improve service access in these areas. Refereed/Peer-reviewed