Effect of Indenter Nose Shape and Layer Configuration on the Quasi-Static Perforation Behaviour of Metal-Plastic Laminates.

This study investigated the perforation resistance behaviour of metal-plastic laminates (MPLs) when they are indented by different nose shapes. Aluminium (Al) and HDPE (high-density polyethylene) layers were bonded with a suitable adhesive in an alternative manner to prepare bilayer and trilayer MPL configurations. Quasi-static perforation experiments were performed with hemispherical, conical and blunt indenters. The effects of nose shape, layer configuration and adhesive on the force-deformation profile, perforation resistance capacity and failure mechanisms were evaluated. The results indicate that for a monolithic layer, the blunt indenter showed the highest perforation energy capacity. The conical and blunt indenters facing Al backed by HDPE gave higher perforation energy. The hemispherical indenter facing HDPE backed by Al was found to be more effective in perforation resistance. Trilayer Al-HDPE-Al showed higher perforation resistance than HDPE-Al-HDPE. Circumferential cracking, radial symmetric cracking and shear plugging were the main failure modes for Al under hemispherical, conical and blunt indenters, respectively. The adhesive contributed to an increase in the perforation energy and peak force to failure in laminates. The adhesive was shown to detach from the Al surface after Al fracturing through crack propagation, and this effect was more pronounced when the indenter faced HDPE at the front of the laminate.

Implementation of advanced radiotherapy technology to improve clinical outcomes in rural NSW.

PROBLEM: Availability of advanced radiotherapy technology to treat cancer is limited in regional Australia. At Central West Cancer Care Centre, the utilisation rate of intensity-modulated radiotherapy and volumetric modulated arc therapy was significantly lower compared to other NSW public health services. Stereotactic ablative body radiotherapy treatment was not available at Central West Cancer Care Centre. DESIGN: To increase the intensity-modulated radiotherapy/volumetric modulated arc therapy utilisation rate and to make stereotactic ablative body radiotherapy treatment available through quality improvement projects with multi-disciplinary collaboration. SETTING: Central West Cancer Care Centre is part of Western NSW Local health District. Central West Cancer Care Centre has two linear accelerators for delivering intensity-modulated radiotherapy, volumetric modulated arc therapy and stereotactic ablative body radiotherapy treatments, and a computed tomography simulator with 4D computed tomography capability. KEY MEASURES FOR IMPROVEMENT: Intensity-modulated radiotherapy/volumetric modulated arc therapy utilisation rate increases to > 65% Stereotactic ablative body radiotherapy available to Central West Cancer Care Centre patients STRATEGY FOR CHANGE: A multi-disciplinary active of team radiation oncologists, medical physics specialists and radiation therapists developed an implementation plan for each treatment technique. EFFECT OF CHANGE: There was a significant increase in use of advanced techniques. The impact on patients included the following: Fewer side effects and improved control of disease as the advanced techniques directed the dose to the tumour and reduced the radiation dose to organ at risk. Treatment completed sooner than conventional radiotherapy, as the required dose required fewer trips to the hospital. Rural and remote patients were not required to travel to a metropolitan centre to have stereotactic ablative body radiotherapy treatment. LESSONS LEARNT: Strong commitment from a trained team and a collaborative approach is important for the implementation of advanced technology in regional centres.

Application of first order kinetics to characterize MTBE natural attenuation in groundwater.

Methyl tertiary butyl ether (MTBE) was a gasoline oxygenate that became widely used in reformulated gasoline as a means to reduce air pollution in the 1990s. Unfortunately, many of the underground storage tanks containing reformulated gasoline experienced subsurface releases which soon became a health concern given the increase in public and private water supplies containing MTBE. Many states responded to this by banning the use of MTBE as an additive, including Connecticut. Although MTBE dissipates by natural attenuation, it continues to be prevalent in groundwater long after the Connecticut ban in 2004. This study estimated the rate of the natural attenuation in groundwater following the Connecticut ban by evaluating the MTBE concentration two years prior to and two years after the MTBE ban at eighty-three monitoring wells from twenty-two retail gasoline stations where MTBE contamination was observed. Sites chosen for this study had not undergone active remediation ensuring no artificial influence to the natural attenuation processes that controls the migration and dissipation of MTBE. Results indicate that MTBE has dissipated in the natural environment, at more than 80% of the sites and at approximately 82% of the individual monitoring wells. In general, dissipation approximated first order kinetics. Dissipation half-lives, calculated using concentration data from the two year period after the ban, ranged from approximately three weeks to just over seven years with an average half-life of 7.3 months with little variability in estimates for different site characteristics. The accuracy of first order estimates to predict further MTBE dissipation were tested by comparing predicted concentrations with those observed after the two year post-ban period; the predicted concentrations closely match the observed concentrations which supports the use of first order kinetics for predictions of this nature.

Concordance between thoracic multidisciplinary meeting recommendations for radiation therapy and actual treatment for lung cancer.

INTRODUCTION: There is limited evidence whether decisions of Thoracic Multidisciplinary Meetings (TMDMs) are reflected in the treatment lung cancer patients actually receive. Aims were to determine concordance between TMDM recommendations for radiotherapy (RT) and actual RT administered and to compare cases that received RT that were referred or not referred from TMDMs. METHOD: A retrospective review of demographic and clinical data for all lung cancer cases within the Auckland-Northland region referred for RT from TMDMs (January-June 2009) and all cases that received RT but were not referred from TMDMs (January-August 2009). RESULTS: Of 110 cases referred for RT from TMDMs, 86 (78%) were offered RT (76 with the same treatment intent) and 78 (71%) received RT. Ten (9%) cases were deemed unsuitable for RT; 7 (6%) deteriorated; 4 (4%) declined or did not attend; 3% other. Fifty-one other cases received RT without TMDM presentation. Cases with remote domicile or recurrent disease were significantly less likely to have been presented at TMDMs. TMDM presentation did not significantly increase transit time to RT. The proportion of RT cases referred from TMDMs had increased substantially since 2004. CONCLUSION: The concordance between TMDM recommendations for RT and both the RT administered and the intent of treatment suggests a useful role for TMDMs. Concordance could be increased by improving RT timeliness and improved education of other disciplines and patients regarding the role of RT. Strategies to increase presentation at TMDM include attention to geographically isolated groups.

Twinning partnerships through International Atomic Energy Agency (IAEA) to improve radiotherapy in common paediatric cancers in low- and mid-income countries.

PURPOSE: The article summarises the current use of radiotherapy (RT) in childhood cancer and suggests methods to improve current practice in regions where outcomes of paediatric cancer patients are inferior to those of high-income countries. METHODS AND MATERIALS: The International Atomic Energy Agency (IAEA) is supporting low- and mid-income countries (LMICs) in upgrading cancer care where nuclear applications, particularly RT, are used. A consensus meeting of experts was invited to advise IAEA on the needs for RT in paediatric cancer patients. The current indications for RT were reviewed, together with regional differences in access, practice and outcome. RESULTS: Regional variations in the use of evidence-based multidisciplinary care including RT were associated with varying outcomes of paediatric cancer patients. The contribution of modern and investigational technology to these differences is uncertain and should be determined in clinical trials. Adequate resources are required to support children through the acute phase of treatment and to permit early recognition and management of late effects. An IAEA sponsored project for prospective data collection to assess the current and future status of radiation treatment in childhood cancer in LMICs has commenced. CONCLUSION: RT remains an essential component of the multidisciplinary management of many paediatric cancers. Excessive variations in outcome are inappropriate and call for action on harmonising training programmes and compliance with evidence-based recommendations. Training projects targeting paediatric cancer care are being implemented and clinical studies comparing new technologies against evidence-based approaches are needed to achieve this goal. The IAEA has an important role in these activities and has commenced prospective data collection in 13 LMICs to monitor trends in treatment techniques and outcomes.

Lung cancer patients in New Zealand initially present to secondary care through the emergency department rather than by referral to a respiratory specialist.

BACKGROUND: The previous study established that lung cancer patients in Auckland-Northland most commonly presented to secondary care through the emergency department (ED). AIM: To further explore the characteristics and presentation of cases presenting through EDs in Auckland. METHODS: Data were collected for all lung cancer cases (2004) in Auckland that initially presented to secondary care via ED RESULTS: Of (478) lung cancer cases diagnosed in Auckland in 2004, 170 cases (36%) presented via ED. ED presentation varied with tumour stage (p<0.0005), ethnicity (p=0.01), and DHB (p=0.004). Of the patients presenting to ED for whom records were available (159; 94%): 107 (67%) had respiratory symptoms; 66 (42%) were GP-referred; of these, 22 had had a CXR; 6 (4%) were already under respiratory surveillance; and 11 (6%) had previously been seen by secondary care regarding the presenting symptoms. All cases (except 1) were admitted. GP referral varied across DHBs (p=0.04) and ethnic groups (p=0.02). Age, gender, and tumour type were not associated with ED presentation. CONCLUSION: Lung cancer patients, especially those of Pacific ethnicity, commonly presented as emergencies, often by-passing primary care. This suggests barriers to, or within, primary care and further research is required to explore the reasons underlying these findings.

Hyperparathyroidism after irradiation for childhood malignancy.

PURPOSE: To examine the occurrence of hyperparathyroidism in a cohort of patients undergoing combined parathyroid and thyroid surgery after previous head-and-neck irradiation for childhood malignancy. METHODS AND MATERIALS: This is a retrospective cohort study for the years 1996 to 2007. The study group comprised patients undergoing surgery in the University of Sydney Endocrine Surgical Unit who had received previous head-and-neck irradiation in childhood and who were identified as having pathologic thyroid and parathyroid characteristics. RESULTS: A total of 53 patients were identified in whom head-and-neck irradiation for the treatment of childhood malignancy had been documented. In each of the cases, thyroid disease was the primary reason for referral for surgery. Five of these patients (10%) were found to exhibit coexisting hyperparathyroidism. The latency period for hyperparathyroidism was less than 20 years in 4 of the 5 cases. There were four conventional parathyroid adenomas and one parathyroid lipoadenoma. All patients exhibited a significant decrease in postoperative calcium levels after surgery. CONCLUSIONS: To our knowledge, this is the first study to document the significant risk of hyperparathyroidism after radiation exposure for childhood malignancy. The timeframe for development of disease is much shorter than that published for individuals who have undergone irradiation for benign diseases. High doses of therapeutic radiation at a young age make childhood survivors of malignancy at especially high risk for developing hyperparathyroidism.

Radiotherapy utilisation in lung cancer in New Zealand: disparities with optimal rates explained.

BACKGROUND AND PURPOSE: The intervention rate (IR) of radiotherapy (RT) is important for health service planning. As actual IRs are commonly lower than those predicted by models, we sought to determine the reasons for this discrepancy, using lung cancer in a mixed urban-rural region of New Zealand (NZ). METHODS: The appropriate utilisation of RT was calculated as the sum of the actual utilisation 3 years post diagnosis (88% of cases deceased), the estimated utilisation of the 12% remaining alive, and the percentage of cases that may have benefited from RT but did not receive it. RESULTS: The actual utilisation was estimated as 43% (range 40-48%). A further 8% of deceased cases may have benefitted from RT (but were not referred), giving an appropriate utilisation of 51%. An additional 3.5% that may have benefitted from RT declined management. The difference from modelled IRs was due to a combination of early mortality, refusal of treatment and assumed higher RT treatment rates for many clinical scenarios. CONCLUSION: The appropriate utilisation of RT was substantially lower than IRs derived from models. The assumptions from which these models were derived may result in over-estimates for resource planning purposes.

Comparison of New Zealand Cancer Registry data with an independent lung cancer audit.

BACKGROUND: Despite the importance of New Zealand Cancer Registry (NZCR) data to research and healthcare decision-making, there has been no previous assessment of the accuracy of NZCR data since mandatory reporting commenced in 1994. AIM: To assess the completeness and accuracy of NZCR lung cancer data. METHOD: An audit of secondary care management in Auckland and Northland of lung cancer patients diagnosed in 2004 provided the opportunity to compare data from regional databases (RD) with NZCR data. RESULTS: Of 565 audit cases, 66 cases (12%) were not included on the NZCR listing. The NZCR listing included 9 eligible cases not identified by RD, 1 duplicate registration and 78 (13%) ineligible cases. Few differences occurred in demographic or tumour details for the 490 cases common to both listings. Tumour staging was available for 97% of cases in RD, and disease extent was recorded for 58% in the NZCR. The latter was more likely to be missing for cases with locally advanced disease (p<0.001), older age (p<0.001), or comorbidity (p<0.001). CONCLUSION: Use of the NZCR alone would have reduced accrual by 12%; disease extent was absent for 42% with a systematic bias towards being unknown for cases with locally advanced disease. Use of NZCR data without recognition of this bias could lead to inappropriate conclusions. Those using NZCR data should be aware of its definitions, methodology and limitations.

Ethnic differences in the management of lung cancer in New Zealand.

BACKGROUND: Major ethnic disparities in lung cancer survival exist in New Zealand, with Mäori having a higher case-fatality ratio than non-Mäori. AIM: To assess whether secondary care management of lung cancer differed by ethnicity and could contribute to ethnic survival disparities. METHODS: An audit of secondary care management in Auckland and Northland of lung cancer patients diagnosed in 2004 permitted comparison of the management of lung cancer in different ethnic groups. RESULTS: The 565 eligible cases comprised: European 378 (67%), Mäori 95 (17%), Pacific Peoples 56 (10%), Asian 23 (4%), and other or unknown ethnicity 13 (2%). In multivariate analysis (adjusting for tumor and patient factors including comorbidity), Mäori were 2.5 times more likely to have locally advanced disease than localized disease compared with Europeans (p < 0.01), and four times less likely to receive curative rather than palliative anticancer treatment compared with Europeans (p < 0.01). Mäori had longer transit times from diagnosis to treatment (p < 0.001). Mäori were more likely to decline treatment and miss appointments than Europeans, although this only partially explained management differences. CONCLUSION: Multiple factors are potentially responsible for the higher case-fatality ratio in Mäori. Such factors include presentation with more advanced disease, lower rates of curative treatment for nonmetastatic disease, and longer transit times from diagnosis to treatment. In this retrospective study, socioeconomic deprivation, comorbidity levels, and failure to accept treatment did not fully explain ethnic differences in management. Further assessment of the underlying issues by prospective evaluation is warranted.

Lung cancer in New Zealand: patterns of secondary care and implications for survival.

INTRODUCTION: The survival of patients with lung cancer in New Zealand is poor compared with Australia and the United States. To determine whether these poorer outcomes were related to secondary care management or to other factors, we documented stage of disease, comorbidities, and initial secondary care management for patients diagnosed with lung cancer in 2004, in Auckland and Northland (New Zealand). These data were compared with international data. METHODS: Cases were identified from regional databases and the New Zealand Cancer Registry. Patient, tumor, and management details were collected from clinical records. RESULTS: Five hundred sixty-five eligible cases were identified: 55% were male, the median age was 69 years, 9% were never-smokers, 81% had documented comorbidity, and 32% belonged to the most deprived socioeconomic quintile. Histopathology was non-small cell lung cancer (NSCLC) in 70%, small-cell lung cancer (SCLC) in 13%, 2% other types, and 15% clinicoradiological diagnoses. At presentation, 70% of NSCLC cases had locally advanced/metastatic disease, and 65% of SCLC cases had extensive disease. Overall, 70% of cases were referred to an anticancer service, and 50% received initial anticancer treatment. Potentially curative treatment was received by 20% of cases: 56% stage I/II, 10% stage III NSCLC, and 58% limited-stage SCLC. CONCLUSIONS: This cohort was characterized by high comorbidity and advanced disease. Although similar to the United Kingdom, initial treatment rates were low in comparison with Australia and the United States, despite similar stage distributions. Overall, 50% of patients, including 30% with early-stage disease, did not receive initial anticancer treatment. Low anticancer treatment rates may contribute to poorer survival outcomes in New Zealand.

Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma.

The role of radiotherapy is well established in the management of most locally advanced and metastatic cancers; however, there has been reluctance to extend this role to melanoma. The reasons can be traced historically to in-vitro and in-vivo data suggesting that melanomas are resistant to radiation. Current findings indicate that these cancers have a wide range of sensitivity to radiation that overlaps extensively with those for common epithelial cancers: indeed, some melanomas show high sensitivity to radiation. Greater incorporation of radiotherapy into multidisciplinary management of melanoma is important because of the typical natural history of the disease (a propensity for both locoregional recurrence and distant metastases) and its poor response to systemic treatment. This review will discuss these issues and preview the strategies being developed for radiotherapy to further improve the care of patients with melanoma.

Radiation therapy in the management of cutaneous melanoma.

The role of RT in the management of melanoma is complex and spans the entire course of the disease. To provide optimal management of patients who have melanoma, radiation oncologists are an integral part of a multidisciplinary team. Appropriate integration of radiation into the management plan can improve locoregional control and alleviate symptoms from meta-static disease. The specific role of RT in locoregional disease is being refined. It is likely that current developments in radiation treatment technology will be applicable to melanoma. These should improve the therapeutic ratio by enhancing the tumoricidal effects of RT without increasing toxicity.

Internal mammary node metastasis from primary cutaneous melanoma on the anterior chest.

BACKGROUND: Direct lymphatic drainage from the skin of the anterior chest and breast to internal mammary lymph nodes does not normally occur. METHODS: Preoperative lymphoscintigraphy was performed in a 55-year-old man with a 3.7 mm-thick primary melanoma on his right anterior chest, who had undergone surgery and radiotherapy to successfully treat a localized lymphosarcoma in his right axilla 35 years earlier. RESULTS: The sentinel node in the lower right internal mammary chain, in the 5th interspace, was removed at the same time as the primary melanoma site was widely excised, and micrometastatic melanoma was subsequently identified in it. Second-tier nodes in the 4th and 3rd right interspaces were therefore removed, and adjuvant radiotherapy was given to the entire internal mammary node chain. CONCLUSIONS: This case demonstrates that major disturbance of normal lymphatic drainage pathways can result from previous surgery and/or radiotherapy. Also, the rarity of this drainage pattern indicates that attempts to identify sentinel nodes in breast cancer patients by injecting tracer into the skin overlying a tumour rather than into the breast tissue immediately adjacent to it are likely to be inaccurate in some patients, because cutaneous injection will not demonstrate the sentinel nodes in the internal mammary chain that are present in up to 40% of patients with a breast cancer.

Transfection of melanoma cells with antisense PAX3 oligonucleotides additively complements cisplatin-induced cytotoxicity.

Advanced melanoma is difficult to treat, in part because of greater resistance to therapy compared with other cancer types. The mechanisms underlying this resistance are not well-understood. One factor that is reported to be involved in melanoma cell survival is PAX3, a transcription factor normally expressed during embryonic development, and which is critically required for development of neural crest-derivatives, including skin melanocytes. PAX3 expression is deregulated in primary melanomas and most melanoma cell lines. Here we have investigated whether targeting PAX3 expression in melanoma cell lines together with chemotherapeutic treatment increases susceptibility to therapeutic cell death. Using PAX3-specific antisense oligodeoxynucleotides (PAX3-AS) to treat melanoma cell lines in vitro, we showed dose-dependent reduction of proliferation of melanoma cells, and induction of apoptosis compared with control treatments. Induction of apoptosis was accompanied by the induction of active caspase-3 in UACC62 and M14 cells, and p53 protein in UACC62 cells. Treatment of melanoma cells with cisplatin induces DNA damage and cytotoxicity, which is thought to be via p53-dependent and -independent mechanisms. Treatment of either p53 mutant (M14) or wild-type (UACC62) melanoma cells with cisplatin, and varying doses of PAX3-AS, resulted in percentages of cells undergoing apoptosis equivalent to the sum of the individual treatments, irrespective of mutation status [e.g., UACC62, 43.8% (1 micromol/L PAX3-AS), 30.1% (20 micromol/L cisplatin), 69.6% (PAX3-AS + cisplatin); M14, 12.6% (1 micromol/L PAX3-AS), 41.5% (40 micromol/L cisplatin), 50.2% (PAX3-AS + cisplatin)]. These data suggest that treatment of melanoma cells with PAX3-AS complements cytotoxicity induced by cisplatin.

Cyclin D1 overexpression in AIDS-related and classic Kaposi sarcoma.

The anatomic distribution and rate of progression vary significantly between acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) and classic KS. The reasons are unclear, but cyclin D1 overexpression is associated with tumor progression in other malignancies. Cyclin D has an important regulatory role in the progression of cell cycle at the G1-S phase due to its effect in phosphorylating the retinoblastoma gene product. Forty-one paraffin-embedded surgical specimens (31 AIDS-related, 10 classic) were examined using streptavidin-biotin-peroxidase immunohistochemistry with monoclonal antibody to cyclin D1. A scoring system based on the intensity and extent of staining was used. The correlations among cyclin D1 expression and clinicopathologic parameters were statistically analyzed. Cyclin D1 overexpression was found in 29% (12/41) of all KS cases. There was a strong correlation between cyclin D1 overexpression and pathologic stage (0% in patch stage, 13% in plaque stage, 50% in nodular stage; P = 0.0017). Classic KS lesions had a higher incidence of cyclin D1 overexpression than AIDS-related lesions (70% vs 16%, P = 0.001). Cyclin D1 overexpression was detected in 78% of the classic nodular lesions and 31% of the AIDS-related nodular lesions (P = 0.03). On multivariate analysis, negative human immunodeficiency virus status (P = 0.001) and nodular lesions (P = 0.007) were strong predictors of cyclin D1 overexpression. Age, gender, recurrence of the tumor, multiplicity, and site of the lesions hold no statistically significant association with cyclin D1 expression on multivariate analysis. In summary, cyclin D1 overexpression was more prevalent in classic lesions and more advanced nodular stage. These findings raise the possibility of a different pathogenetic mechanism in the progression of AIDS-related KS and classic KS.

Radiosensitization of vinorelbine and gemcitabine in NCI-H460 non-small-cell lung cancer cells.

PURPOSE: Results from recent clinical studies of gemcitabine and vinorelbine have encouraged the use of this combination concurrently with radiotherapy in the treatment of non-small-cell lung cancer, although preclinical data are limited. The present study aimed to quantify the in vitro interaction and radiosensitizing effect of gemcitabine and vinorelbine individually and in combination. METHODS AND MATERIALS: Cytotoxicity was measured by exposing NCI-H460 cells to gemcitabine and/or vinorelbine simultaneously or sequentially, followed by irradiation at 0-10 Gy. Clonogenic cell survival assays were performed. Flow cytometry was used to measure the effects of both drug and radiation on cell cycle distribution. Apoptosis was assessed by morphologic criteria, by sub-G1 changes using flow cytometry assay, and by Annexin-V binding assay. RESULTS: Both drugs showed single-agent activity against NCI-H460 cells and targeted different phases of the cell cycle. When both drugs were used in combination, they showed schedule-dependent interaction. An antagonistic effect was observed with simultaneous exposure to the two drugs. The optimum combination schedule was sequential exposure to vinorelbine followed by gemcitabine 24 h later. Both drugs showed radiosensitization effects. The radiosensitization effect of gemcitabine was evident when radiation was given immediately after 4-h incubation. However, the radiosensitization effect of vinorelbine was time dependent and observed with radiation given at 24 h postincubation. Apoptosis induced by gemcitabine increased gradually, reaching 20% at 72 h posttreatment. In contrast, apoptotic cell death was an early feature in vinorelbine-treated cells, reaching approximately 40% at 24 h. CONCLUSIONS: The individual cytotoxic effects of gemcitabine and vinorelbine on NCI-H460 cells are phase specific, and the combined effect of gemcitabine and vinorelbine is sequence dependent. The radiosensitizing effects of both drugs seem to be related to enhanced apoptosis.

Long-term review of a breast conservation series and patterns of care over 18 years.

BACKGROUND: Multiple randomized trials of breast conservation compared with mastectomy in early breast cancer have validated equivalence of survival. Overwhelmingly the standard management of breast conservation includes surgical removal of the tumour, axillary dissection, postoperative breast irradiation, and adjuvant systemic therapy as appropriate. The outcomes are reviewed of 832 women with early breast cancer treated by local resection and irradiation at Royal Prince Alfred Hospital over an 18 year period, with particular emphasis on the changing patterns of practice. METHODS: Between September 1978 and May 1996, 832 women with early stage breast cancer were treated with conservative surgery and radiation therapy. The changes in patient, tumour and treatment factors were analysed over this time period. The outcomes of local recurrence and survival were recorded. Trends in patterns of these variables were evaluated by dividing the 18 years accrual period into three consecutive periods (1978-1983, n = 28; 1984-1990, n = 392; 1991-1996, n = 412). RESULTS: At a median follow up of 76 months, the 5 and 10 year actuarial local recurrence rates were 4% and 6%, respectively. Half of the local recurrences were at the primary site. Young age, extensive intraduct carcinoma, oestrogen receptor (ER) status and extranodal spread were predictive of local recurrence on multivariate analysis. The 5 and 10 year overall survival rates were 88% and 73%, respectively. Actuarial 5 year local recurrence (4%, 6%, 2%) and survival (96%, 88%, 92%) rates varied little across the three time intervals. There was an increase in median age from 46 to 56 years over the accrual period, with no change in median primary tumour size (1.5 cm). There were significant histopathological improvements in reporting margin status and ER status. Surgically, the median number of axillary lymph nodes retrieved (14) did not alter significantly. With respect to adjuvant therapies, irradiation of lymph nodes regions decreased over time. The proportion of patients receiving adjuvant hormones or chemotherapy increased significantly (18%, 35%, 54%). CONCLUSIONS: The low local recurrence rate and high survival are consistent with published literature for early breast cancer. Changes in practice during the accrual period included improvements in histopathological reporting, a reduction in irradiation of lymph node regions, and an increase in the use of systemic therapy. These changes parallel international recommendations regarding the optimal management of early breast cancer.