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Purpose: The aim of this study was to evaluate oncologists' opinions about the use of ionizing radiation in medical imaging of oncology patients., Methods: An electronic survey was e-mailed to 2,725 oncologists at the top 50 National Cancer Institute-funded cancer centers. The survey focused on opinions on CT dose reduction in oncology patients and current philosophies behind long-term imaging in these patients., Results: The response rate was 15% (415 of 2,725). Eighty-two percent of respondents stated that their patients or families have expressed anxiety regarding radiation dose from medical imaging. Although fewer than half of oncologists (48%) did not know whether CT dose reduction techniques were used at their institutions, only 25% were concerned that small lesions may be missed with low-dose CT techniques. The majority of oncologists (63%) follow National Comprehensive Cancer Network guidelines for imaging follow-up, while the remainder follow other national guidelines such as those of the Children's Oncology Group, the American Society of Clinical Oncology, or clinical trials. Ninety percent of respondents believe that long-term surveillance in oncology patients is warranted, particularly in patients with breast cancer, melanoma, sarcoma, and pediatric malignancies. The majority of oncologists would consider the use of low-dose CT imaging in specific patient populations: (1) children and young women, (2) those with malignancies that do not routinely metastasize to the liver, and (3) patients undergoing surveillance imaging., Conclusions: Cumulative radiation exposure is a concern for patients and oncologists. Among oncologists, there is support for long-term imaging surveillance despite lack of national guidelines., (Published by Elsevier Inc.)

Background: cancer-testis (CT) antigens, frequently expressed in human germline cells but not in somatic tissues, may become aberrantly reexpressed in different cancer types. The aim of this study was to investigate the expression of CT antigens in breast cancer., Patients and Methods: a total of 100 selected invasive breast cancers, including 50 estrogen receptor (ER) positive/HER2 negative and 50 triple negative (TN), were examined for NY-ESO-1 and MAGE-A expression by immunohistochemistry., Results: a significantly higher expression of MAGE-A and NY-ESO-1 was detected in TN breast cancers compared with ER-positive tumors (P = 0.04). MAGE-A expression was detected in 13 (26%) TN cancers compared with 5 (10%) ER-positive tumors (P = 0.07). NY-ESO-1 expression was confirmed in nine (18%) TN tumor samples compared with two (4%) ER-positive tumors., Conclusions: MAGE-A and NY-ESO-1 CT antigens are expressed in a substantial proportion of TN breast cancers. Because of the limited therapeutic options for this group of patients, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.

Objective: Timely access to necessary medicines that Australians need is one of the four pillars of the Australian Government's National Medicines Policy. We were interested to determine whether there was a change in the time taken for medicines to be listed once recommended by the Pharmaceutical Benefits Advisory Committee (PBAC)., Methods: Descriptive statistics were used to show the pattern of recommendations for PBAC meetings from 1999 to 2003. For successful recommendations, we developed a linear regression model to analyze the time to list from the PBAC meeting to date of listing (time to list). The model determined whether this time had changed over the 4-year period, and the reasons for any changes., Results: The PBAC made 307 positive recommendations at its 17 meetings over the study period. Ninety percent resulted in a Pharmaceutical Benefits Scheme (PBS) listing on or before April 1, 2005. Eighty-two percent of the recommendations made in 1999 and 2000 resulted in early or on-time listings. In 2001, 2002, and 2003, the comparable proportions were 67%, 68%, and 75%. Mean times to list for the years from 1999 to 2003 were similar (approximately 23 weeks), except in 2001 where it was 30 weeks., Conclusions: Over the study period, 90% of all PBAC recommendations resulted in a PBS listing. In 2001 there was a statistically significant increase in the mean time to list. In addition, it appears that recommendations for new listings and new indications (medicines that are likely to result in substantial Government expenditure) were associated with a longer time to list.

Background: This study was designed to ascertain whether immunohistochemical methods could improve the detection of metastases in primary breast-cancer patients whose axillary lymph nodes were classified, by conventional methods, as disease free., Methods: Ipsilateral lymph nodes (negative for metastases by routine histology) from 736 patients (participants in Trial V of the International [Ludwig] Breast Cancer Study) were examined by serial sectioning and staining with haematoxylin and eosin (two sections from each of six levels) and by immunohistochemistry of a single section (with two anticytokeratins AE-1 and CAM 5.2). After median follow-up of 12 years, disease-free and overall survival were estimated by Kaplan-Meier methods., Findings: Occult nodal metastases were detected by serial sectioning and haematoxylin and eosin in 52 (7%) of 736 patients and by immunohistochemistry in 148 (20%). Only two (3%) of 64 invasive lobular or mixed invasive lobular and ductal cancers had node micrometastases, detected by haematoxylin and eosin, compared with 25 (39%) by immunohistochemistry. Occult metastases, detected by either method, were associated with significantly poor disease-free and overall survival in postmenopausal but not in premenopausal patients. Immunohistochemically detected occult lymph-node metastases remained an independent and highly significant predictor of recurrence even after control for tumour grade, tumour size, oestrogen-receptor status, vascular invasion, and treatment assignment (hazard ratio 1.79 [95% CI 1.17-2.74], p=0.007)., Interpretation: The immunohistochemical examination of ipsilateral axillary lymph nodes is a reliable, prognostically valuable, and simple method for the detection of occult nodal metastases. Immunohistochemistry is recommended as a standard method of node examination in postmenopausal patients.

The immunocytochemical demonstration, using monoclonal antibodies, of diverse cellular constituents has improved our understanding of many aspects of oncology. This review will focus on this approach to facilitate the detection of human tumors, improve their histological classification and provide functional parameters with potential aetiological, prognostic and/or therapeutic value.

42 patients with metastatic breast carcinoma were treated with aminoglutethimide, which inhibits adrenal steroid hormone synthesis. Treatment was stopped in 2 patients before response could be assessed; of the other 40, 15 (37.5%) had an objective response, 1 (2.5%) showed a response in bone but not in soft tissue, and 4 (10%) had complete or very great relief of metastatic bone pain but no radiological evidence of improvement. 19 (53%) of 36 patients with bone metastases responded to treatment (15 had X-ray evidence and 4 had pain relief), as did 5 (45%) of 11 patients with soft tissue metastases, 2 (25%) of 8 with malignant marrow infiltration, 1 (14%) of 7 with lung metastases, and none of 13 with liver metastases. Response was commonest in patients who had previously responded to other forms of endocrine therapy. Side-effects, usually mild and transient, occurred in a few patients; the most important were an initial period of somnolence in 9 patients and a rash in 5.

The ability of a radiolabelled monoclonal antibody, LICR-LON-M8 (M8), to locate metastatic breast carcinomas has been investigated. The scans generated by M8, either when labelled with radioiodine, or when conjugated with diethylenetriamine-pentaacetic acid (DTPA) and labelled with radioactive indium (111In), have been compared with X-rays and 99mTc-methyl diphosphonate (MDP) bone scans. All 10 patients with skeletal metastases had positive 111In-DTPA-M8 scans and the overall correlation with X-rays and MDP scans was good but varied with the region studied. By contrast, radioiodinated M8 did not detect metastases at any site. The discrepancies between 111In-DTPA-M8 images and conventional techniques may be related to the different stages in the evolution and development of the lesion at which the various techniques detect bone metastases.

222 patients with disseminated breast cancer have been randomised to receive either a combination of hormone therapies using tamoxifen, aminoglutethimide with hydrocortisone, and danazol (TAD), or tamoxifen alone. The response to the combination was significantly better (43%) than that to tamoxifen alone (31%). Patients who relapsed after response or failed to respond to tamoxifen were subsequently treated with aminoglutethimide and then, if possible, with danazol. Some patients who received TAD were subsequently treated with alternative endocrine therapy, which was usually medroxyprogesterone acetate. Of the 111 patients who initially received tamoxifen, 43 responded to the tamoxifen and/or subsequent endocrine therapy. Of the 111 patients who initially received TAD, 50 responded. Although the duration of response to TAD was the same as for tamoxifen, the TAD patients achieved remission more quickly. The total time in endocrine remission for patients receiving TAD is 303 months to date, compared with 264 months for patients receiving tamoxifen. Survival for patients randomised to receive TAD or tamoxifen is the same.

A radioimmunoassay (RIA) was developed for the quantitative measurement of a glycoprotein which was purified from human milk-fat-globule membrane (MFGM) and termed MFGM-pg 70. The assay with a sensitivity of detecting 30 ng of MFGM-pg 70/ml was employed to quantitate the levels of MFGM-gp 70 shed in supernatants from primary cultures of normal and malignant human breast cells and from various established cell lines of human mammary including myoepithelial and fibroblast and non-mammary malignant epithelial cells. The RIA for MFGM-gp 70 showed that the amount of antigen shed was much higher in supernatants from normal mammary epithelial cells compared with their malignant counterparts grown in primary culture and with those from established cell lines of malignant mammary epithelial cells. No detectable antigen was found in supernatants from cultures of normal myoepithelial-like cell lines or primary cultures of fibroblast cells from breast, or cell lines of squamous carcinomas of head and neck and tongue, renal cell carcinoma and teratoma. Trypsinization of mammary epithelial cells from both primary and established lines resulted in the release of most of the antigen from the surface of the cells, suggesting the presence of this molecule on the cell's surface. Following trypsinization, approximately 99% of the cells was viable, indicating that the release of the antigen in supernatants was due to shedding and not cell death. The levels of MFGM-pg 70 in spent media were unaffected by the lactogenic hormones such as prolactin or insulin. The RIA for MFGM-gp 70 provides a sensitive and quantitative means to in vitro study the synthesis of a membrane glycoprotein from human mammary epithelium.

Nineteen biochemical parameters, most of which have been individually advocated as tumour-index-substances for breast cancer, were measured in 51 patients with breast disease, 42 of whom had active breast cancer. Seven of these parameters were raised in more than half of the 17 patients of the series with overt metastases; these were serum ferritin (88%), C-reactive protein (87%), carcinoembryonic antigen (81%), acid glycoprotein (75%), total alkaline phosphatase (64%), sialyl transferase (56%), andthe urinary hydroxyproline/creatinine ratio (73%). The incidence of biochemical abnormalities in patients in this group compared favourably with the results of physical methods of detecting metastases. 7 of 16 further patients without evidence of distant metastases, but who had a poor prognosis as judged by histology of the primary tumour and axillary lymph-nodes, had abnormalities of at least one of the seven parameters. 3 of these patients have relapsed within a year of mastectomy. The results suggest that these biochemical tests could assist in monitoring metastatic disease and could indicate at the time of mastectomy, patients who might benefit from immediate systemic therapy in addition to local treatment of their breast carcinomas.

23 (60%) of 38 human breast carcinomas had significant in-vitro osteolytic activity. All patients presenting with bone metastases or hypercalcaemia had active tumours. Over a subsequent three-year follow-up period, bone metastases did not develop in any of the 15 patients with inactive tumours, and metastases at other sites developed in only 2. Of the 23 patients with active tumours, 7 either had, or have since developed bone metastases; in 4 of these hypercalcaemia also developed. 14 tumours, chosen at random, were tested for in-vitro osteolytic activity in the presence and absence of aspirin, which inhibits prostaglandin synthetase. The activity of 8 of the 9 osteolytically active tumours was significantly, though not completely inhibited by aspirin. Although the number of patients is limited, these results indicate that the in-vitro osteolysis assay may detect substances, perhaps including prostaglandins, produced by breast tumours which affect prognosis and contribute to the subsequent formation of bone metastases.

The value of a monoclonal antibody, LICR-LON-Fib-75 (Fib-75), which mediates complement lysis and recognises an antigen present on all epithelial-tumour cells so far studied but not on lymphoid cells or bone-marrow stem cells, in clearing infiltrated bone marrow was assessed. Chromium-51-release and trypan-blue-exclusion assays showed that no tumour cells were viable after exposure to Fib-75 and complement except when large clumps (greater than 500 cells) were present, whereas Fib-75 had no significant effect on bone-marrow cells, as judged by colony-forming-unit and pluripotential-stem-cell assays.

Of ten tumour markers measured every 3 months after mastectomy in patients with apparently localised primary breast cancer, plasma levels of alkaline phosphatase, carcinoembryonic antigen, and gamma-glutamyl transpeptidase were the most useful in detecting metastatic disease. With these three tests a "lead interval" of 3 months or more was obtained in about half the 23 patients who developed overt metases. Clinical examination, chest X-ray, and these three markers proved the most useful combination of tests in screening for metastases, since at least one test was abnormal in 46 of 47 patients at the time of the development of metastases as judged by more detailed physical tests.