Factors Predictive of Treatment by Australian Breast Surgeons of Invasive Female Breast Cancer by Mastectomy rather than Breast Conserving Surgery

Roder, David,Zorbas, Helen,Kollias, James,Pyke, Chris,Walters, David,Campbell, Ian,Taylor, Corey,Webster, Fleur Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: The National Breast Cancer Audit Database of the Society of Breast Surgeons of Australia and New Zealand is used by surgeons to monitor treatment quality and for research. About 60% of early invasive female breast cancers in Australia are recorded. The objectives of this study are: (1) to investigate associations of socio-demographic, health-system and clinical characteristics with treatment of invasive female breast cancer by mastectomy compared with breast conserving surgery; and (2) to consider service delivery implications. Materials and Methods: Bi-variable and multivariable analyses of associations of characteristics with surgery type for cancers diagnosed in 1998-2010. Results: Of 30,299 invasive cases analysed, 11,729 (39%) were treated by mastectomy as opposed to breast conserving surgery. This proportion did not vary by diagnostic year (p>0.200). With major city residence as the reference category, the relative rate (95% confidence limits) of mastectomy was 1.03 (0.99, 1.07) for women from inner regional areas and 1.05 (1.01, 1.10) for those from more remote areas. Low annual surgeon case load (${\leq}10$) was predictive of mastectomy, with a relative rate of 1.08 (1.03, 1.14) when compared with higher case loads. Tumour size was also predictive, with a relative rate of 1.05 (1.01, 1.10) for large cancers (40+ mm) compared with smaller cancers (<30 mm). These associations were confirmed in multiple logistic regression analysis. Conclusions: Results confirm previous studies showing higher mastectomy rates for residents of more remote areas, those treated by surgeons with low case loads, and those with large cancers. Reasons require further study, including possible effects of surgeon and woman's choice and access to radiotherapy services.

Adherence to Recommended Treatments for Early Invasive Breast Cancer: Decisions of Women Attending Surgeons in the Breast Cancer Audit of Australia and New Zealand

Roder, David M.,Silva, Primali De,Zorbas, Helen N.,Webster, Fleur,Kollias, James,Pyke, Chris M.,Campbell, Ian D. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Aim: The study aim was to determine the frequency with which women decline clinicians' treatment recommendations and variations in this frequency by age, cancer and service descriptors. Design: The study included 36,775 women diagnosed with early invasive breast cancer in 1998-2005 and attending Australian and New Zealand breast surgeons. Rate ratios for declining treatment were examined by descriptor, using bilateral and multiple logistic regression analyses. Proportional hazards regression was used in exploratory analyses of associations with breast cancer death. Results: 3.4% of women declined a recommended treatment of some type, ranging from 2.6% for women under 40 years to 5.8% for those aged 80 years or more, and with parallel increases by age presenting for declining radiotherapy (p<0.001) and axillary surgery (p=0.006). Multiple regression confirmed that common predictors of declining various treatments included low surgeon case load, treatment outside major city centres, and older age. Histological features suggesting a favourable prognosis were often predictive of declining various treatments, although reverse findings also applied with women with positive nodal status being more likely to decline a mastectomy and those with larger tumours more likely to decline chemotherapy. While survival analyses lacked statistical power due to small numbers, higher risks of breast cancer death were suggested, after adjusting for age and conventional clinical risk factors, (1) for women not receiving breast surgery for unstated reasons (RR=2.29; p<0.001); and (2) although not approaching statistical significance $p{\geq}0.200$), for women declining radiotherapy (RR=1.22), a systemic therapy (RR1.11), and more specifically, chemotherapy (RR=1.41). Conclusions: Women have the right to choose their treatments but reasons for declining recommendations require further study to ensure that choices are well informed and clinical outcomes are optimized.

Metastatic Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia Over Three Decades

Roder, David,Karapetis, Christos S,Wattchow, David,Moore, James,Singhal, Nimit,Joshi, Rohit,Keefe, Dorothy,Fusco, Kellie,Buranyi-Trevarton, Dianne,Sharplin, Greg,Price, Timothy J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

Overexpressed Drosophila DNA Methyltransferase 2 Isoform C Interacts with Hsp70 in Vivo

Roder, Karim Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.4

Shen and colleagues (Lin et al., 2004) have recently shown that overexpression of the Drosophila DNA methyltransferase 2 isoform C, dDnmt2c, extended life span of fruit flies, probably due to increased expression of small heat shock proteins such as Hsp22 or Hsp26. Here, I demonstrate with immunoprecipitations that overexpressed dDnmt2c interacts with endogenous Hsp70 protein in vivo in S2 cells. However, its C-terminal half, dDnmt2c(178-345) forms approximately 10-fold more Hsp70-containing protein complexe than wild-type dDnmt2c. Overexpressed dDnmt2c(178-345) but not the full length dDnmt2c is able to increase endogenous mRNA levels of the small heat shock proteins, Hsp26 and Hsp22. I provide evidence that dDnmt2c(178-345) increases Hsp26 promoter activity via two heat shock elements, HSE6 and HSE7. Simultaneously overexpressed Hsp40 or a dominant negative form of heat shock factor abrogates the dDnmt2c(178-345)-dependent increase in Hsp26 transcription. The data support a model in which the activation of heat shock factor normally found as an inactive monomer bound to chaperones is linked to the overexpressed C-terminus of dDnmt2c. Despite the differences observed in flies and S2 cells, these findings provide a possible explanation for the extended lifespan in dDnmt2c-overexpressing flies with increased levels of small heat shock proteins.

Breast Screening and Breast Cancer Survival in Aboriginal and Torres Strait Islander Women of Australia

Roder, David,Webster, Fleur,Zorbas, Helen,Sinclair, Sue Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Aboriginal and Torres Strait Islander people comprise about 2.5% of the Australian population. Cancer registry data indicate that their breast cancer survivals are lower than for other women but the completeness and accuracy of Indigenous descriptors on registries are uncertain. We followed women receiving mammography screening in BreastScreen to determine differences in screening experiences and survivals from breast cancer by Aboriginal and Torres Strait Islander status, as recorded by BreastScreen. This status is self-reported and used in BreastScreen accreditation, and is considered to be more accurate. The study included breast cancers diagnosed during the period of screening and after leaving the screening program. Design: Least square regression models were used to compare screening experiences and outcomes adjusted for age, geographic remoteness, socio-economic disadvantage, screening period and round during 1996-2005. Survival of breast cancer patients from all causes and from breast cancer specifically was compared for the 1991-2006 diagnostic period using linked cancer-registry data. Cox proportional hazards regression was used to adjust for socio-demographic differences, screening period, and where available, tumour size, nodal status and proximity of diagnosis to time of screen. Results: After adjustment for socio-demographic differences and screening period, Aboriginal and Torres Strait Islander women participated less frequently than other women in screening and re-screening although this difference appeared to be diminishing; were less likely to attend post-screening assessment within the recommended 28 days if recalled for assessment; had an elevated ductal carcinoma in situ but not invasive cancer detection rate; had larger breast cancers; and were more likely than other women to be treated by mastectomy than complete local excision. Linked cancer registry data indicated that five-year year survivals of breast cancer cases from all causes of death were 81% for Aboriginal and Torres Strait Islander women, compared with 90% for other women, and that the former had larger breast cancers that were more likely to have nodal spread at diagnosis. After adjusting for socio-demographic factors, tumour size, nodal spread and time from last screen to diagnosis, Aboriginal and Torres Strait Islander women had approximately twice the risk of death from breast cancer as other women. Conclusions: Aboriginal and Torres Strait Islander women have less favourable screening experiences and those diagnosed with breast cancer (either during the screening period or after leaving the screening program) have lower survivals that persist after adjustment for socio-demographic differences, tumour size and nodal status.

What Roles should Population-based Cancer Registries be Playing in the 21st Century? Reflections on the Asian Cancer Registry Forum, Bangkok, February 2014

Roder, David Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Cancer registries have fundamental roles in cancer surveillance, research, and health services planning, monitoring and evaluation. Many are now assuming a broader role by contributing data for health-service management, alongside data inputs from other registries and administrative data sets. These data are being integrated into de-identified databases using privacy-protecting data linkage practices. Structured pathology reporting is increasing registry access to staging and other prognostic descriptors. Registry directions need to vary, depending on local need, barriers and opportunities. Flexibility and adaptability will be essential to optimize registry contributions to cancer control.

Influence of Service Characteristics on High Priority Performance Indicators and Standards in the BreastScreen Australia Program

Roder, David Murray,Ward, Gail Heather,Farshid, Gelareh,Gill, Peter Grantley Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Data from BreastScreen Australia Screening and Assessment Services (SAS) for 2002-2010 were analysed to determine whether some SAS characteristics were more conducive that others to high screening performance, as indicated by high priority performance indicators and standards. Materials And Methods: Indicators investigated related to: numbers of benign open biopsies, screen-detected invasive cancers, and interval cancers, and wait times between screening and assessment. Multivariate Poisson regression was undertaken using as candidate predictors of performance, SAS size (screening volume), urban or rural location, year of screening, accreditation status, and percentages of clients from culturally and linguistically diverse backgrounds, rural and remote areas, and socio-economically disadvantaged areas. Results: Performance standards for benign biopsies and invasive cancer detection were uniformly met irrespective of SAS location and size. The interval cancer standard was also met, except in 2003 when the 95% confidence interval of the rate still incorporated the national standard. Performance indicators improved over time for: benign open biopsy for second or subsequent screening rounds; rates of invasive breast cancer detection for second or subsequent screening rounds; and rates of small cancer detection. No differences were found over time in interval cancer rates. Interval cancer rates did not differ between non-metropolitan and metropolitan SAS, although state-wide SAS had lower rates. The standard for wait time between screening and assessment (being assessed ${\leq}28$ days) was mostly unmet and this applied in particular to SAS with high percentages of culturally and linguistically diverse women in their screening populations. Conclusions: Gains in performance were observed, and all performance standards were met irrespective of SAS characteristics, except wait times to assessment. Additional descriptive data should be collected on SAS characteristics, and their associations with favourable screening performance, as these may be important when deciding on SAS design

Risk Factors for Poorer Breast Cancer Outcomes in Residents of Remote Areas of Australia

Roder, David,Zorbas, Helen,Kollias, James,Pyke, Chris,Walters, David,Campbell, Ian,Taylor, Corey,Webster, Fleur Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

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 socio-economic 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.

Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia over three Decades

Roder, David,Karapetis, Christos S,Wattchow, David,Moore, James,Singhal, Nimit,Joshi, Rohit,Keefe, Dorothy,Fusco, Kellie,Powell, Kate,Eckert, Marion,Price, Timothy J Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

Survival From Synchronous Bilateral Breast Cancer: The Experience of Surgeons Participating in the Breast Audit of the Society of Breast Surgeons of Australia and New Zealand

Roder, David,Silva, Primali de,Zorbas, Helen,Kollias, James,Malycha, Peter,Pyke, Chris,Campbell, Ian,Webster, Fleur Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Previous studies generally indicate that synchronous bilateral breast cancers (SBBC) have an equivalent or moderately poorer survival compared with unilateral cases. The prognostic characteristics of SBBC would be relevant when planning adjuvant therapies and follow-up medical surveillance. The frequency of SBBC among early breast cancers in clinical settings in Australia and New Zealand was investigated, plus their prognostic significance, using the Breast Cancer Audit Database of the Society of Breast Surgeons of Australia and New Zealand, which covered an estimated 60% of early invasive lesions in those countries. Design: Rate ratios (95% confidence limits) of SBBC were investigated among 35,370 female breast cancer cases by age of woman, histology type, grade, tumour diameter, nodal status, lymphatic/vascular invasion and oestrogen receptor status. Univariate and multivariable disease-specific survival analyses were undertaken. Results: 2.3% of cases were found to be SBBC (i.e., diagnoses occurring within 3 months). The figure increased from 1.4% in women less than 40 years to 4.1% in those aged 80 years or more. Disease-specific survivals did not vary by SBBC status (p=0.206). After adjusting for age, histology type, diameter, grade, nodal status, lymphatic/vascular invasion, and oestrogen receptor status, the relative risk of breast cancer death for SBBC was 1.17 (95% CL: 0.91, 1.51). After adjusting for favourable prognostic factors more common in SBBC cases (i.e., histology type, grade, lymphatic/vascular invasion, and oestrogen receptor status), the relative risk of breast cancer death for SBBC was 1.42 (95% CL: 1.10, 1.82). After adjusting for unfavourable prognostic factors more common in SBBC cases (i.e., older age and large tumour diameter), the relative risk of breast cancer death for SBBC was 0.98 (95% CL: 0.76, 1.26). Conclusions: Results confirm previous findings of an equivalent or moderately poorer survival for SBBC but indicate that SBBC status is likely to be an important prognostic indicator for some cases.