Assessing impact of organised breast screening across small residential areas-development and internal validation of a prediction model.

Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post-diagnostic survivals through lead-time and related effects, as well as mortality reductions. Linked cancer and BreastScreen data at four hospitals (n = 2,039) were used to investigate whether screened cases had higher recorded survivals in 13 small areas, using breast cancer deaths as the outcome (M1), and a risk of death score derived from TNM stage, grade, histology type, hormone receptor status, and related variables (M2). M1 indicated lower risk of death in screened cases in 12 of the 13 areas, achieving statistical significance (p < .05) in 5. M2 indicated lower risk scores in screened cases in all 13 areas, achieving statistical significance in 12. For cases recently screened at diagnosis (<6 months), statistically significant reductions applied in 8 areas (M1) and all 13 areas (M2). Screening effects are more detectable in small areas using these risk scores than death itself as the outcome variable. An added advantage is the application of risk scores for providing a marker of screening effect soon after diagnosis.

Influences on decision for mastectomy in patients eligible for breast conserving surgery.

Increasing emphasis is being placed on low mastectomy rates. Our objective was to investigate factors influencing rates of mastectomy and breast conserving surgery. A group of 171 patients (27%) who could have had breast conserving surgery (BCS) but chose mastectomy was identified as well as all patients who underwent BCS over a 6 year period. A questionnaire asking patient's attitudes to factors which could influence their choice of operation was compiled and sent to this study group. Results showed surgical advice to be the most important factor, with significantly more influence in BCS patients. No significant difference was found in distance to treatment between the groups. Shorter duration radiotherapy would have made 47% of mastectomy patients more likely to accept BCS. BCS rates are a poor measure of quality of patient care. More emphasis should be put on choices offered to patients rather than overall uptake of a specific choice.

Factors predictive of immediate breast reconstruction following mastectomy for invasive breast cancer in Australia.

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.

Inhibition of A. carbonarius growth and reduction of ochratoxin A by bacteria and yeast composites of technological importance in culture media and beverages.

Five composites of yeast and six of bacterial isolates from fermented products were studied, in order to assess their ability to inhibit Aspergillus carbonarius growth and reduce OTA concentration in culture media and beverages. The antagonistic effect of the above composites against A. carbonarius growth was studied in synthetic grape medium of pH 3.5 and a(w) 0.98, 0.95, 0.92 after incubation at 25°C. Different combinations of initial inocula of bacteria or yeast composites and fungi were used (10(2)cfu/mL vs 10(5)spores/mL; 10(5)cfu/mL vs 10(2)spores/mL; and 10(5)cfu/mL vs 10(5)spores/mL). Regarding the OTA reduction experiment, 10(3) and 10(7)cfu/mL of the bacteria and yeast composites were inoculated in liquid media of different pH (3.0, 4.0, 5.0, and 6.1 or 6.5) and initial OTA concentration (50 and 100µg/L) and incubated at 30°C. Moreover, grape juice, red wine, and beer were supplemented with 100µg/L of OTA and inoculated with composites of 16 yeasts (16YM) and 29 bacterial (29BM) strains (10(7)cfu/mL) to estimate the kinetics of OTA reduction at 25°C for 5days. Fungal inhibition and OTA reduction were calculated in comparison to control samples. None of the bacterial composites inhibited A. carbonarius growth. The high inoculum of yeast composites (10(5) cfu/mL) showed more efficient fungal inhibition compared to cell density of 10(2) cfu/mL. All yeast composites showed higher OTA reduction (up to 65%) compared to bacteria (2-25%), at all studied assays. The maximum OTA reduction was obtained at pH 3.0 by almost all yeast composites. For all studied beverages the decrease in OTA concentration was higher by yeasts (16YM) compared to bacteria (29BM). The highest OTA reduction was observed in grape juice (ca 32%) followed by wine (ca 22%), and beer (ca 12%). The present findings may assist in the control of A. carbonarius growth and OTA production in fermented foodstuffs by the use of proper strains of technological importance.

Feasibility study on the MammoSite in early-stage breast cancer: initial experience.

The aims of this study were to evaluate the feasibility, practicality, efficacy and safety of the delivery of accelerated partial breast irradiation using the MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0, T2N0, Grade I-II invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The MammoSite was inserted 20-37 days postoperatively. External beam radiation therapy to the whole breast commenced 1-5 days after accelerated partial breast irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed spontaneously within 3-5 days. No Grade III or higher acute toxicity or local infection was recorded. The ease of insertion and accuracy of dosimetry makes the MammoSite suitable for use in properly selected women with early-stage breast cancer in a trial setting.

Phenotypic similarities in bilateral breast cancer.

Bilateral breast cancers that develop at similar times in an individual are likely to have been subjected to similar hormonal, environmental and genetic influences during tumourogenesis compared with metachronous tumours. As such, it is possible that tumour phenotype in synchronous bilateral breast cancer may display similar biological characteristics. The aim of this study was to identify phenotypic similarities between synchronous and metachronous bilateral breast cancers which may suggest a common origin. Thirty-three cases of synchronous and 46 cases of metachronous bilateral breast cancer that displayed similar tumour type were analysed for concordance in relation to various histological and immunohistochemical parameters. A higher level of concordance was demonstrated for synchronous cases with the highest level seen for oestrogen receptor. It is likely that this is related to similar tumourogenic pathways occurring at equivalent exposure times to various environmental and hormonal influences, although, in a proportion of cases, inherited genetic factors may play a role.

Identification of carcinoma cells in peripheral blood samples of patients with advanced breast carcinoma using RT-PCR amplification of CK7 and MUC1.

We have undertaken a pilot study to attempt to identify circulating carcinoma cells in a series of patients with advanced breast carcinoma, using reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA of epithelial specific antigens. Using this method to amplify mRNA of MUC1 and cytokeratin 7 (CK7) the sensitivity of the technique was demonstrated by means of diluted concentrations of "spiked MCF7" cells in whole blood, showing a detection limit of 1 in 10(6) (CK7) and 1 in 10(5) (MUC1). Positive results were obtained from the peripheral blood of all nine female patients with advanced breast cancer for CK7 and eight of the nine patients for MUC1. CK7 was however detected in five of 11 healthy controls (eight females, three males) and MUC1 in one of the 11 controls. None of the control group were positive for both CK7 and MUC1, in contrast to eight of the nine patients with advanced breast carcinoma who were positive for both markers. The RT-PCR method thus appears sufficiently sensitive to identify circulating tumour cells in peripheral blood samples from patients with advanced breast carcinoma. However a high proportion of false-positive results was seen in the control population. More extensive investigation is required before the technique is likely to be of benefit clinically.

Removal of two sentinel nodes accurately stages the axilla in breast cancer.

BACKGROUND: Assessment of lymph node status in breast cancer is still necessary for staging. Sentinel lymph node biopsy (SNB) may provide accurate staging with less morbidity than axillary clearance. The aim of this study was to assess the effect of the number of sentinel nodes removed on the false-negative rate. METHODS: Data were collected prospectively from 395 women undergoing SNB for breast cancer, between June 1995 and December 2001. All nodes that were hot and/or blue were removed and analysed. RESULTS: During this interval 136 patients who had SNB were lymph node positive. The median number of sentinel nodes removed was two (range one to five). The overall false-negative rate of SNB in these women was 7.1 per cent. If only one sentinel node had been removed, the false-negative rate would have been 16.5 per cent. The removal of more than two nodes had no effect on axillary staging in all but two women. CONCLUSION: In early breast cancer, when there were multiple sentinel nodes, removal of two sentinel nodes significantly reduced the false-negative rate compared with removal of one node. Removing more than two sentinel nodes did not significantly reduce the false-negative rate further.

Clinical impact of false-negative sentinel node biopsy in primary breast cancer.

BACKGROUND: The aim was to assess the false-negative sentinel node biopsy rate in women with early breast cancer and its implications in patient treatment. METHODS: Between January 1995 and March 2001, 328 consecutive patients with clinically lymph node-negative primary operable breast cancer underwent lymphatic mapping and sentinel node biopsy using a combination of preoperative lymphoscintigraphy and/or blue dye. All underwent immediate axillary dissection. The intraoperative success rate in sentinel node identification, false-negative rate, predictive value of negative sentinel node status and overall accuracy were assessed. The clinical features and primary tumour characteristics for each false-negative case were reviewed. RESULTS: The sentinel node was identified in 285 (86.9 per cent) of 328 women. The false-negative rate was 7.9 per cent (eight of 101). Most members of the breast multidisciplinary team would have instituted adjuvant systemic therapy for six false-negative cases based on clinical features and primary tumour histology. In all, only two (0.7 per cent) of 285 women who had sentinel node biopsy may have had their management and survival prospects potentially jeopardized owing to a false-negative sentinel node. CONCLUSION: The results of this study suggest that the clinical impact of a false-negative sentinel node is low.

Prognostic significance of synchronous and metachronous bilateral breast cancer.

Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast, but the clinical significance of this development is unclear. The purpose of this study was to assess the impact of synchronous bilateral breast cancer or the development of a metachronous contralateral breast primary on the prognosis. In a series of 3210 women age < or = 70 years treated between 1975 and 1995 for primary operable breast cancer, 106 were identified to have bilateral breast cancer. Of these women, 26 were noted to have synchronous bilateral breast primaries (0.8%), and 80 developed a contralateral breast cancer after treatment for an initial primary breast cancer. Using life-tables analysis, there was a significant difference in survival between women with unilateral breast cancer, those with synchronous bilateral breast cancers, and those with metachronous contralateral breast with survivals at 16 years of 53.8%, 42.4%, and 60.1%, respectively (p < 0.0001), from the date of the diagnosis of the first primary tumor. There was no difference in survival seen between the three groups when survival was calculated from the date of diagnosis of the second primary in cases of metachronous contralateral breast cancer (p = 0.31). When contralateral breast cancer was incorporated as a time-dependent covariate in a Cox multivariate model together with the three factors used to determine the Nottingham Prognostic Index (invasive tumor size, grade, and lymph node stage), contralateral breast cancer continued to be a significant prognostic determinant (p = 0.02). The survival of women with synchronous bilateral breast cancer or metachronous breast cancers diagnosed within 2 years of the original primary was worse than those with unilateral disease. However, the time duration to metachronous contralateral breast cancer did not have prognostic significance in a multivariate model compared with the prognostic features of the original primary.

Quality assurance in a multidisciplinary symptomatic breast assessment clinic.

BACKGROUND: Although quality assurance guidelines for surgeons have been issued and adopted for use in population-based breast screening programs in Australia, similar guidelines are unavailable for women referred with symptomatic breast problems. METHODS: Six hundred and ninety-six women who attended the Royal Adelaide Hospital Women's Health Centre between February and November 1998 for investigation and management of a new breast-related complaint were prospectively evaluated. Investigation strategies and outcomes of the initial consultation were determined and the results compared with the performance quality standards for symptomatic breast disease according to the British Association of Surgical Oncology (BASO) Breast Surgeons' Group. RESULTS: A breast lump was the presenting symptom in 45%, while breast pain was present in 26%. Ninety per cent of women referred with breast symptoms were given a definitive benign or malignant diagnosis at the initial clinic visit. Although the median time delay between the date of general practitioner referral and breast clinic appointments for all patients was < or =7 days, the time delay for 'urgent' cases was not met according to BASO performance indicators. All other Royal Adelaide Hospital Breast Clinic audit data were within the range suggested by BASO performance indicators for new consultations in a symptomatic breast assessment clinic. CONCLUSIONS: A multidisciplinary breast clinic in a public hospital setting is able to provide clinical services to symptomatic women, with the majority of patients obtaining a confident diagnosis at the first presentation. Performance indicators for symptomatic breast disease are useful in identifying inadequacies at the clerical or clinical level which, following the implementation of subsequent changes, may lead to improvement in patient outcomes.

Clinical and histological factors associated with sentinel node identification in breast cancer.

BACKGROUND: Although sentinel lymph node biopsy is likely to be offered as a method of assessing nodal status in primary breast cancer, the inability to identify the sentinel node at the time of surgery will limit the number of patients who may benefit from the procedure. The purpose of the present study was to identify factors that are associated with intraoperative identification of the sentinel node(s). METHODS: Between September 1995 and May 1999, lymphatic mapping using a combination of preoperative lymphoscintigraphy and/or blue dye was performed on 169 consecutive patients with clinically lymph node-negative primary operable breast cancer. Clinical and histological factors were assessed using univariate and multivariate analysis to determine those that were associated with intraoperative identification of the sentinel node. RESULTS: The sentinel node was identified at the time of surgery in 142 cases (84%). Of the clinical factors assessed, preoperative identification of the sentinel node on lymphoscintigraphy (P < 0.0001), use of blue dye in combination with isotope (P = 0.001), symptomatic palpable tumours (P < 0.05) and the experience of the surgeon (P = 0.03) were significant in identifying the sentinel node at operation. No histological factor was associated with intraoperative identification of the sentinel node. Using multivariate analysis, positive identification of the sentinel node on lymphoscintigram, the experience of the surgeon and the use of both blue dye and isotope for sentinel node mapping were independent factors associated with intraoperative sentinel node identification. The lymphoscintigram result was the strongest independent factor according to its beta value, a measure of the weight of significance. CONCLUSION: Patients undergoing sentinel lymph node mapping and biopsy should be warned of the possibility of failure of sentinel node identification at operation. Our results suggest that the best predictor of intraoperative sentinel node identification is the visualization of the sentinel node on preoperative lymphoscintigraphy. The result of the lymhoscintigram may allow for additional preoperative counselling of the patient regarding the success or failure of sentinel node biopsy. Technical factors such as the experience and diligence of the surgeon, as well as the sentinel node mapping technique, are also important in determining the success of the procedure.

Value of contralateral surveillance mammography for primary breast cancer follow-up.

Mammographic screening of the contralateral breast is often advocated during follow-up of women previously treated for primary operable breast cancer. The purpose of this study was to determine the value of this investigation. Between 1987 and 1995 a total of 5102 contralateral screening mammograms were performed biennially on 2511 women aged

Sentinel node biopsy in breast cancer: recommendations for surgeons, pathologists, nuclear physicians and radiologists in Australia and New Zealand.

BACKGROUND: Assessment of axillary lymph node status is necessary for patients with invasive breast cancer. Sentinel node biopsy is a new minimally invasive technique that may provide accurate assessment of regional lymph node status while limiting the morbidity associated with axillary clearance. METHODS: A workshop conducted in Adelaide in November 1998 aimed to assess current sentinel node mapping and biopsy techniques, and make recommendations regarding its application in the surgical management of early breast cancer in Australia and New Zealand. RESULTS: At the conclusion of the workshop, a consensus was reached regarding indications, exclusions, sentinel node mapping/biopsy technique, nuclear medicine requirements, pathology and safety of sentinel node biopsy in breast cancer. It was agreed that a feasibility study according to an agreed prospective protocol was necessary to validate the technique by breast surgeons. Surgeons that satisfied validation criteria for the feasibility study could then consider a prospective randomized study comparing sentinel node biopsy with standard axillary dissection. CONCLUSIONS: Sentinel node biopsy in breast cancer involves close cooperation between members of a multidisciplinary team including surgeons, nuclear physicians, pathologists and radiologists. Although the technique has the potential to reduce morbidity associated with axillary surgery, surgical performance in this area will need to be closely monitored to ensure that the technique does not fall into disrepute by adversely affecting breast cancer prognosis.

Loss of heterozygosity in bilateral breast cancer.

Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age < 50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.

Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma.

BACKGROUND: Many empiric protocols are used to detect metastases in sentinel lymph nodes (SLNs), but comparison of the efficacy of these methods is impractical because tissue is lost in processing, making reassessment with another policy difficult. Consequently, performance indicators of this test are largely unknown. DESIGN: The authors retrospectively examined 112 SLNs removed from 89 patients with breast carcinoma treated at the authors' institution and used the histologic data to devise a mathematic model of a SLN with Matlab modeling software. The authors simulated examination of this computer-generated (virtual) lymph node according to several macroscopic and histologic sampling protocols and for each protocol assessed the probability of detecting micrometastases of specified sizes. The authors used published costing figures to estimate the cost of the policies. RESULTS: Direct comparison of 6 sectioning strategies currently in use by pathology laboratories showed the chances of detecting a 500-microm metastasis ranged from 20% to 75%. Four of the 6 protocols had a less than 30% chance of detecting metastases of this size. The detection rate of smaller metastases was poorer. Cost was not a good discriminator because some policies were more efficient than others. CONCLUSIONS: The detection of metastases is highly dependent on the methods used to look for them. The authors' simulations suggest that commonly used methods of examining lymph nodes have high false-negative rates, particularly for small metastases. There is an urgent need for pathologists and clinicians to agree on the minimum size of SLN metastases that will be sought by histology and set standard methods for examining these lymph nodes.

Effect of evening primrose oil on clinically diagnosed fibroadenomas.

The effects of oil of evening primrose oil on fibroadenomas was assessed over a 6-month period. Eleven out of 21 (52%) of fibroadenomas receiving evening primrose oil and 8 out of 19 (42%) controls reduced in size. This study demonstrates that evening primrose oil does not significantly effect the natural history of breast fibroadenomas.