Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer.

The generation of antitumour immunity depends on the nature of dendritic cell (DC)-tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy.

Changes in survival after breast cancer: improvements in diagnosis or treatment?

We have compared 5-year survival rates in two cohorts of women diagnosed with breast cancer in Brisbane, Australia, between 1981-1984 and 1990-1994. Tumours diagnosed in the early 1990s were significantly smaller and less likely to have nodal involvement than those diagnosed 10 years earlier (P<0.0001). The size difference was particularly striking for women aged over 50 at diagnosis, those targeted for screening. Five-year survival was greater among women diagnosed in the 1990s (84% vs. 74%; hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.81). After adjusting for the effects of tumour size and nodal status this difference was reduced, but women diagnosed more recently still showed improved survival (HR 0.75; 95% CI 0.56-1.01) and disease-free survival (HR 0.72; 0.56-0.92) at 5 years. This suggests that both earlier diagnosis and changes in breast cancer treatment have contributed to improved breast cancer survival.

Perceived sensitivity of mammographic screening: women's views on test accuracy and financial compensation for missed cancers.

OBJECTIVES: To estimate women's expectations of the accuracy of screening mammography and to explore attitudes towards compensation for missed cancers. DESIGN: Cross sectional survey (by telephone). SETTING: Australia; population-based survey conducted in April 1996. PARTICIPANTS: Random sample of women aged 30-69 years. A total of 2935 women completed the Breast Health Survey (adjusted response rate 65%). A random sample of 115 completed this sub-survey on perceived sensitivity of mammographic screening and compensation for missed cancers. RESULTS: About one third of women (32.2%, 95% CI 23.7, 40.7) had an unrealistically high expectation of the sensitivity of screening mammography, reporting it to be 95% or higher. Approximately 40% of the women (43.5%, 95% CI 34.4, 52.6) thought that screening mammography should pick up all cancers (should have a sensitivity of 100%). Just under half the women (45.2%, 95% CI 36.1, 54.3) said financial compensation should be awarded for a cancer missed by screening mammography even if the cancer was missed as a consequence of the small failure rate of the test. Younger women living in metropolitan areas and women who had realistic expectations of the accuracy of the tests were more likely to favour financial compensation. CONCLUSION: Unrealistically high expectations of the sensitivity of screening mammography were common in this group of women. Many women favoured financial compensation for missed cancers even if the cancer was missed solely because of the failure rate of the test. Public education is required to inform women of the limited sensitivity of breast cancer tests but this may not reduce claims for financial compensation when cancers are missed.

Breast cancer: current issues in diagnosis and treatment.

The diagnosis and treatment of breast cancer in Australia has changed in response to new technologies and cultural influences which have emphasized the importance of psychological and social aspects of breast cancer. In this review article, recent developments are examined in relation to current surgical practice. Changes in the incidence of breast cancer, the effect of mammographic screening on the outcome of treatment, the increasing use of breast-conserving surgery, the timing of surgery in relation to the menstrual cycle and the importance of risk factors for breast cancer are all considered. Breast cancer is a potentially curable disease. Early detection and conservative surgery provide a framework for disease control.

Estimating treatment cost functions for progressive diseases: a multiproduct approach with an application to breast cancer.

Using the theory of multiproduct cost functions, a treatment cost function is derived for diseases which progress through a number of stages. The output classes are conceived as the stages at detection of the disease, with the unit of output within each class being the treated case. The derivation clarifies the assumptions underlying various specific functional forms for the treatment cost function. An empirical application to the treatment of breast cancer is provided, producing evidence on an important issue in the economics of screening programs, viz. whether detection of breast cancer at an earlier stage results in treatment cost savings.

The costs of treating breast cancer in Australia and the implications for breast cancer screening.

The aim of the study was to determine if there is a relationship between the stage of breast cancer at the time of detection and the costs of treatment and to assess whether any such relationship would have an influence on the cost of a mammographic screening programme. A retrospective analysis of the stage at presentation for primary breast cancer and the treatment costs over the duration of treatment was made. Multiple regression analysis was employed, with treatment cost as the dependent variable and categorical variables to represent stage at detection. A total of 301 women whose treatment for breast cancer commenced at the Royal Brisbane Hospital participated in the study. A statistically significant relationship was found between the stage of disease at the time of detection and subsequent treatment costs; more advanced stages of disease incurred higher treatment costs. This relationship was robust even after taking into account the age of patients, their discharge status, and differences between patients in the duration of treatment. When the effect of earlier detection on treatment cost was assessed in relation to a breast screening programme, cost savings were estimated to be in the range of 8-36% of total screening costs. There are treatment cost savings to be gained from breast cancer screening as a result of the detection of earlier stages of disease. These treatment cost savings should be offset against the cost of a mammographic screening programme.

PCNA immunostaining in breast cancer.

Expression of proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic value in patients with certain types of cancer. The aim of this study was to determine if the abundance of PCNA is inversely correlated with survival of patients with breast cancer. Paraffin blocks were available from 68 patients, all of whom had been followed clinically for at least 5 years. Sections from 20 patients showed no reactivity to PCNA and were excluded from the study because it was not possible to distinguish between true negatives and false negatives (those due to poor fixation of the original specimens). The PCNA index (the number of stained cancer cells as a percentage of the total number of cancer cells present) was calculated for the remaining 48 patients. Results were analysed by Wilcoxon's rank sum test (two tailed) and Pearson's correlation coefficient. There was no statistical difference between the PCNA indices of those patients dead from their disease within 5 years of diagnosis compared with those alive and without signs of breast cancer at 5 years. There was also no correlation between PCNA index and size of the cancer, involvement of axillary lymph nodes, time to recurrence or time to death. There was, however, a significant correlation between PCNA index and histological grade (P = 0.029). It appears that PCNA staining of stored paraffin sections is of little prognostic value in patients with breast cancer.

Dirofilariasis in Australia: unusual cause of a breast lump.

A breast lump due to infestation with Dirofilaria repens is reported in a Sri Lankan student residing in Brisbane. Although human infestation with this parasite is not uncommon in certain Asian countries, this is the first report of such a lesion occurring in Australia.

Spontaneous rupture of the liver associated with amyloidosis.

Fatal spontaneous rupture of the liver is described in a 46-year-old women with hepatic amyloidosis diagnosed premortem by liver biopsy. An autopsy revealed systemic amyloidosis, with no evidence of an underlying chronic inflammatory condition, infection, or immunocyte dyscrasia. By computerized search, this is only the third reported case of spontaneous rupture of the liver complicating amyloidosis.

The detection of early breast cancer: three-year results from a diagnostic breast clinic.

The initial results from a diagnostic breast clinic in which clinical examination, x-ray mammography and ultrasound are used to establish a diagnosis during a single patient-visit are described. In 3461 patient-visits, 82 histologically-proven breast cancers were detected. Fifty-two per cent of these cancers were 2 cm or less in diameter and 61% had no axillary lymph-node metastases. Fifteen cancers were impalpable lesions which were detected by mammography alone. The over-all malignant-to-benign biopsy ratio was 1:2.7; for impalpable tumours, this ratio was 1:3.9. The role of such a diagnostic breast clinic is discussed, and attention is drawn to a relatively low attendance of women in the "high-risk" age group of over 50 years of age.

One hundred cases of arteriovenous fistula for haemodialysis access: the effect of cigarette smoking on patency.

The results of 100 radiocephalic arteriovenous fistulae formed in 85 patients to provide access for haemodialysis have been assessed. First fistulae had an immediate patency of 90.5% and a patency predicted by life table analysis of 78% at 1 year. An additional 15 fistulae were formed after initial failure in 13 patients, and the predicted patency for all fistulae was 76% at 1 year and 73% at 2 years, with no subsequent failures during the period of the study. Access was established and maintained in 77 patients (90.6%) using the first or a subsequent radiocephalic fistula, and the requirement for other access procedures was low. There was a significantly higher incidence of early and late fistula failure in those patients who were cigarette smokers.