Relationships in Canada between mortality from tumours of the gastrointestinal tract and marital status.

The mortality from tumours of the gastrointestinal tract in the Canadian population in 1970-72 was 16% higher in single than in married men (on the basis of age-adjusted rates), 25% higher in widowed men and 28% higher in divorced men. All these differences were unlikely to be due to chance. The rates were 4% higher for single women, 14% higher for widows and 22% higher for divorced women, compared with the married. The differences for single and divorced women were not significant. Substantial excess mortality was found in the unmarried for tumours of the mouth, pharynx and esophagus, and rectum; for tumours of the stomach and colon the excess was small or nonexistent. This variation between sites suggests that systematic errors in the census data used as denominators are not responsible for the high mortality for the unmarried from certain tumours. The effect is found in conditions for which treatment can have made little difference (e.g., a 75% excess mortality for tumours of the esophagus in single men compared with married) and in conditions for which differences in the use of medical facilities may have been important (e.g., a 44% excess mortality for tumours of the rectum in widowers).     

Zoladex® plus tamoxifen versus zoladex® alone in pre- and peri-menopausal metastatic breast cancer

Phase II studies examining the endocrinological and clinical efficacy of Zoladex® and Zoladex® plus tamoxifen have been examined in pre- and peri-menopausal women with advanced breast cancer. No adverse endocrinological interaction between the drugs have been observed. Although a higher proportion of static disease was observed with the combination of the drugs, which possibly occurred at the expense of partial remissions, the time to disease progression was extended in women who received Zoladex® plus tamoxifen. Remissions were primarily restricted to patients whose tumours were ER positive. Only occasional responses were seen in ER negative disease. This was especially evident where the ER negative tumours were EGF-R positive and showed high rates of cell proliferation.     

In vitro estrogen-binding by human breast carcinomas.

Patients whose breast carcinomas possess only low concentrations of a receptor molecule that binds estrogens with high affinity are unlikely to respond to hormonal manipulative therapy when the disease recurs. The estrogen-binding capacity of 106 breast carcinomas was measured by an in vitro method and was expressed per milligram wet weight and in some cases related to the concentration of deoxyribonucleic acid (DNA) of the tumours. The ability of tumors to bind 3H-estradiol ranged from 0 to 1.3 fm/mg in pre- and perenopausal women, and from 0 to 16.8 fm/mg in postmenopausal women. Menopausal status or serum concentrations of endogenous estrogen, or both, should therefore be considered when tumours are classified into low and high estrogen-binding capacity. It is not necessary to carry out Scatchard analysis for every tumour, and expressing estradiol binding on the basis of DNA concentration may be preferable to expressing in on a wet-weight basis.     

Overweight in relation to tumour size and axillary lymph node involvement in postmenopausal breast cancer patients—Differences between women invited to vs. not invited to mammography in a randomized screening trial

Objectives: Overweight is associated with advanced stage at diagnosis in breast cancer patients. This could be explained by specific tumour characteristics or tumour promoting factors in the obese, but a diagnostic delay could also be of importance. Mammographic screening has caused a change towards diagnosis of less advanced tumours. This study investigates invitation to mammographic screening and the association between overweight and tumour size/axillary lymph node involvement at breast cancer diagnosis in postmenopausal women. Methods: In 1976 a randomized mammographic screening trial, inviting 50% of all women aged 45–69 was set up in Malmö, Sweden. The present analysis examined overweight (body mass index ≥25) as a determinant for large tumours (>20 mm) and axillary lymph node involvement in postmenopausal women. These associations were studied separately in patients diagnosed prior to the mammographic screening trial, in invited women and in non-invited subjects (controls). In all, 2478 postmenopausal women were diagnosed with invasive breast cancer in these groups between 1961 and 1991. Logistic regression analysis allowed adjustment for other potential determinants of tumours size and axillary lymph node involvement. Results: In women diagnosed before the onset of the screening trial and in women not invited to mammography in the trial (controls), overweight was positively associated with large tumour size and axillary node involvement. There was no statistically significant association between overweight and these factors in women invited to mammographic screening. Conclusion: Invitation to mammographic screening may be particularly important for overweight postmenopausal women in order to detect breast tumours early.     

CT abnormalities of the pituitary in hyperprolactinaemic women with normal or equivocal sellae radiologically.

Sixteen young women with hyperprolactinaemia and normal or equivocal sella in radiographs underwent computed tomography using a Siemens Somatom II. In all but one case an abnormality was found. The sella was full in seven and partially empty in nine. A tumour was visible in six of the full and in four of the partially empty sellae. All but one of the 10 tumours was unilateral, and in seven the pituitary stalk was deviated away from the tumour. After administration of intravenous contrast (Urografin) four tumours showed diffuse enhancement, four ring enhancement, and two enhanced less than adjacent normal pituitary tissue. Two of the tumours have been subsequently shown histologically to be prolactinomas. Prolactin response to thyrotrophin-releasing hormone predicted a tumour in seven out of eight with visible tumours but also in three out of four without visible tumours; using metoclopramide, a tumour was predicted in six out of seven with tumours, but again in three out of four without visible tumours. Such results question the value of dynamic tests for the discrimination of tumours. We conclude that practically all women with sustained hyperprolactinaemia and a normal or equivocal sella radiologically have pituitary disease.     

Oestrogen receptors and survival in early breast cancer.

Oestrogen receptor status was related to survival in 414 patients with primary breast cancer. Women with oestrogen receptors in their tumours survived significantly longer than those without receptors; this was true for both premenopausal and postmenopausal women and also when the patients were subdivided into those with and without axillary metastases. Patients with axillary metastases and no oestrogen receptors in their tumours had the worst prognosis, while women with axillary metastases and oestrogen receptors had a death rate similar to that of women with no axillary metastases and no receptors. Patients without oestrogen receptors and with no axillary metastases were identified as a high-risk group, and it would seem appropriate to include such patients in future trials for adjuvant therapy in early breast cancer.     

Circulating macrophage colony stimulating factor as a marker of tumour progression

Tumour expression of the macrophage colony stimulating factor (CSF-1 or MCSF) has been associated with an adverse prognosis in breast cancer, through an effect on the promotion of metastasis. The aim of the present study was to evaluate the clinical relevance of high circulating CSF-1 levels in patients with newly diagnosed breast tumours and correlate CSF-1 with clinico-pathological parameters. A secondary aim was to also measure CSF-1 in patients with other tumour types and at different stages of disease. Using a commercially available ELISA, pre-treatment plasma levels of CSF-1 were assessed, in 471 consecutive patients diagnosed with breast tumours, in 70 patients with newly diagnosed cancer of the head & neck, in 32 men with prostate cancer metastatic to bone and in 39 women with advanced metastatic breast cancer. Mean CSF-1 levels were significantly higher in patients with locally advanced (p <.015) or metastatic breast tumours (p <.048) and in a group of primary breast cancer patients (n = 26) selected for intensive chemotherapy because of multiple adverse tumour characteristics (p <.0002). Mean CSF-1 was also higher in patients younger than 35 years (p <.02) and in post-menopausal patients (p <.03). There was no significant association with tumour histologic type, grade, or other individual histopathologic parameters. No significant association was found between pre-treatment CSF-1 and overall/relapse free survival. Median CSF-1 levels were dramatically higher in patients with newly diagnosed tumours of the head & neck (604 pg/ml), in men with prostate cancer metastatic to bone (627 pg/ml) and women with advanced metastatic breast cancer (867 pg/ml) than those seen in patients with newly diagnosed breast tumours (334 pg/ml). Our data support the hypothesis that CSF-1 may play a functional role in tumour progression to metastasis as has previously been reported in animal models.     

Epidemiology of central nervous system tumors in Karlovac area (Croatia), 1995-2010

The aim of this study was to provide an overview of the central nervous system (CNS) tumours epidemiology in Karlovac region, over the 1995-2010 period. We analyzed data on 359 patients (194 men and 165 women), diagnosed with CNS tumours according to the World Health Organization's diagnostic criteria, in period 1995-2010. The data were obtained from the Neurology and Neurosurgery Department, including other medical records. The data were analysed with t-test and chi-square test. A total of 359 cases of tumours in CNS were recorded for the period of 1995-2010, with slight predominance of men (194;54.0%) over women (165;46.0%). Under the assumption of gender equality, we did not detect a significant gender difference in tumour diagnosis (p = 0.279). Mean age at the diagnosis was 64.1 +/- 12.6 years, with significant gender difference: mean age at diagnosis for men was 62.8 +/- 11.6 years, while for women it was 65.7 +/- 13.5 (p = 0.029). The commonest type of all tumours was metastases (144;40.1%). When only primary tumours were analysed, the commonest type was glioblastoma (125;58.15%), followed by meningeoma (44;20.5%). The remaining types were much less frequent, with i.e. 5 recorded cases of the following three types: astrocytoma, ependimoma and oligodendroglyoma (2.3%). These results suggest a commonly encountered epidemiological profile in the region, with commonest metastases, and glioblastoma as the most common primary tumour. Due to difficulties related to patient gravitating hospitals admittance and overall small sample size for more detailed analyses, it remains for future studies to determine potential association of the Homeland war (1991-1995) and the occurrence of CNS tumours.     

Fluorescence in situ hybridisation analysis and ovarian histology of women with Turner syndrome presenting with Y-chromosomal material: a correlation between oral epithelial cells,lymphocytes and ovarian tissue

The early detection of Y-chromosomal material in women with Turner syndrome (TS) is of great importance due to a relatively high risk of gonadal tumour development. Using fluorescence in situ hybridisation (FISH) analysis, we studied the presence of three different Y-specific sequences (SRY, Ycen and Yq12) in three different tissues (oral epithelial cells, lymphocytes and ovarian tissue) of twelve TS women. We have also described their ovarian histology. Two of the women (17%) had gonadal tumours. In five women where ovarian tissue was available, the presence of Y-chromosomal material in oral epithelial cells and lymphocytes correlated to the presence of Y-chromosomal material in the gonads. We therefore conclude that FISH analysis of oral epithelial cells and/or lymphocytes is a valuable complement to karyotyping for the early detection of Y-chromosomal material in TS women.     

Surgical issues surrounding use of aromatase inhibitors

There are important surgical issues related to the use of the third generation aromatase inhibitors in both the neoadjuvant and adjuvant settings. Neoadjuvant hormone therapy is effective at downstaging tumours, particularly large tumours initially thought to be inoperable or requiring mastectomy. Randomised trials have shown that the newer aromatase inhibitors letrozole and anastrozole increase the numbers of women who are suitable for breast-conservation compared with tamoxifen, and that letrozole is superior to tamoxifen in terms of clinical response.

Aromatase inhibitors are most effective in ER-rich tumours and are clinically and biologically effective in both HER2 positive and negative tumours, whereas HER2 positive tumours show a level of resistance to tamoxifen.

In neoadjuvant studies comparing aromatase inhibitors with tamoxifen, the duration of use has been 3–4 months, by which time any response is usually evident but longer treatment periods produce continued shrinkage and response. The re-excision rate following breast conservation surgery after neoadjuvant hormone therapy is favourable compared with the rates following immediate wide local excision. Local recurrence rates are acceptable in patients undergoing neoadjuvant therapy and breast-conserving surgery providing post-operative radiotherapy is given.

Adjuvant aromatase inhibitors, as well as having an effect on metastatic disease and survival, reduce local and regional recurrence.     

Androgens and breast cancer risk

Transdermal testosterone supplementation is a treatment option for postmenopausal women with distressful decreased libido. Side effects are minor, but there is a long-term safety concern with respect to breast cancer, as women with high testosterone serum levels appear to be at a significantly increased risk to have or to develop breast cancer within a few years. Epidemiological studies of sufficient duration to study long-term effects of testosterone supplementation are limited, both in number and in methodological quality and are, therefore, inconclusive. Preclinical studies do not provide evidence for an androgen receptor-mediated stimulating effect of androgens on breast epithelium. However, one biologically plausible possibility, which cannot be ruled out, is that exogenous androgens become mitogenic after aromatization into bioactive oestradiol, either in peripheral fat or within the breast or even within small occult tumours. The evidence available so far makes counselling women interested in testosterone supplementation for distressful low sexual desire, more of an art than science.     

Audit of public education campaign to encourage earlier detection of malignant melanoma.

OBJECTIVES--To evaluate a public campaign to encourage earlier referral and treatment of primary cutaneous malignant melanoma and thus reduce mortality related to melanoma. DESIGN--Production and distribution of educational material aimed at adults. Update information sent to general practitioners before campaign. Analysis of data on melanoma before and after campaign in June 1985. SETTING--West of Scotland, population 2.7 million. MAIN OUTCOME MEASURES--Total numbers of referrals per month to melanoma clinic, numbers of melanomas diagnosed, change in distribution of thickness, and mortality before and after introducing the campaign. RESULTS--Referrals to the pigmented lesion clinic increased by 278%, from five a week in June-July 1984 to 19 a week in June-July 1985. Twice as many women as men were referred to the clinic (49% of referrals were of women aged under 65). The numbers of newly diagnosed primary cutaneous melanoma were 63 (12/month) in January-May 1985 and 146 (21/month) in June-December 1985, an increase of 131%. The percentage of tumours detected that were less than 1.5 mm thick rose significantly by 16% (95% confidence interval 11% to 19%), from 38% (328) in 1979-84 to 54% (592) in 1985-9. Mortality began to fall in women from 1988. CONCLUSIONS--The public education campaign succeeded in reducing the absolute number of thick tumours and melanoma related mortality in women.     

Breast self-examination: importance of technique in early diagnosis.

Shortly after diagnosis of breast cancer 416 patients were interviewed about their use of screening procedures and the method of tumour detection. Although 72% reported that they performed breast self-examination (BSE), only 12% actually inspected and palpated their breasts monthly. BSE was not significantly associated with tumour size or involvement of the lymph nodes; however, thorough inspection was associated with smaller tumours, and careful palpation with the absence of palpable nodes. Of those who no longer or never had examined their breasts 40% reported having annual breast examinations by their physician and had significantly smaller tumours than did the others. Most of the women (86%) reported having detected their own tumours, and BSE did not significantly increase the likelihood of self-detection. The frequency of use of screening procedures was similar in a sample of women without breast cancer.     

Characterization of the relationship between FLI1 and immune infiltrate level in tumour immune microenvironment for breast cancer

Breast cancer is the most common cancer and the leading cause of cancer death among women in the world. Tumour-infiltrating lymphocytes were defined as the white blood cells left in the vasculature and localized in tumours. Recently, tumour-infiltrating lymphocytes were found to be associated with good prognosis and response to immunotherapy in tumours. In this study, to examine the influence of FLI1 in immune system in breast cancer, we interrogated the relationship between the FLI1 expression levels with infiltration levels of 28 immune cell types. By splitting the breast cancer samples into high and low expression FLI1 subtypes, we found that the high expression FLI1 subtype was enriched in many immune cell types, and the up-regulated differentially expressed genes between them were enriched in immune system processes, immune-related KEGG pathways and biological processes. In addition, many important immune-related features were found to be positively correlated with the FLI1 expression level. Furthermore, we found that the FLI1 was correlated with the immune-related genes. Our findings may provide useful help for recognizing the relationship between tumour immune microenvironment and FLI1, and may unravel clinical outcomes and immunotherapy utility for FLI1 in breast cancer.     

Bone mineral content in normally menstruating women with hyperprolactinaemia

Decreased bone density has been reported in women with hyperprolactinaemia due to pituitary tumours. We identified a number of seemingly healthy women with hyperprolactinaemia, i.e. a serum prolactin concentration exceeding 500 mU/l (25 micrograms/l) on three occasions, during a study in 1980/1981 of a representative population sample of greater than 1,400 women in seven different age strata (range 26-72 years). We compared vertebral bone mineral content and bone mineral areal content in 5 hyperprolactinaemic normally menstruating 50-year-old women with that of 6 controls matched for age and menstrual status but found no difference. Since the degree of prolactin elevation was similar in our study group to that previously reported for hyperprolactinaemic subjects with pituitary tumours and the time of exposure to raised hormone concentration appears to be of the same magnitude, other hormonal changes than hyperprolactinaemia per se seem to be the cause of low bone mineral content in women with hyperprolactinaemia and amenorrhoea.     

Estrogen receptor status of breast cancer in Ontario

Data from a number of studies of breast cancer have suggested that after the ages associated with the menopause the rates of estrogen-receptor-positive tumours increase with age, whereas the rates of estrogen-receptor-negative tumours do not. Previous investigators studied cases in specific treatment centres, so there was a possibility that the findings were influenced by differences in patterns of case referral by age. A review of all the cases of breast cancer diagnosed in Ontario women in 1981 and assayed for estrogen receptors, however, confirmed the earlier findings. The results showed that the incidence of estrogen-receptor-positive and estrogen-receptor-negative tumours increased at about the same rate before age 45, but thereafter an increase in incidence was seen only for estrogen-receptor-positive tumours. These differences in patterns of incidence suggest the possibility that the two types of tumour may have different etiologic factors.     

The role of thallium-201 and pentavalent dimercaptosuccinic acid for staging cartilaginous tumours

INTRODUCTION: Heterogeneity of cartilage tumours may confound accurate diagnosis and grading resulting in under and over treatment. Improved preoperative assessment of malignancy and grade would be invaluable for developing a rational plan for treatment. We examined correlations between nuclear tracer avidity and malignancy grade in cartilage tumours. METHODS: Between 1996 and 2000, 92 consecutive patients with cartilaginous tumours (50 benign, 42 non-metastatic malignant) underwent nuclear scanning. Thallium-201 (TL-201) and pentavalent dimercaptosuccinic acid (DMSAV) were used as nuclear isotopes. Scanning with these agents was performed on separate days 48 hours apart. Static and SPECT images were obtained at 30 m and 4 h after injection of nuclear tracer. Pathology review was undertaken blinded to the results of the nuclear scans and correlations between histologic results and trace uptake at 4 hours examined. RESULTS: 25 patients with negative DMSAV had benign tumours. 15/17 tumours with positive TL-201 had malignant tumours. 11/13 patients with both positive DMSAV and TL-201 scans had intermediate or high grade tumours and 4 of these developed metastases. We have developed an algorithm for the management of patients with tumours that aims to avoid over treatment of low grade tumours and under treatment of high grade tumours. CONCLUSION: Functional nuclear scanning with TL-201 and DMSAV complements other imaging modalities in the management of cartilaginous tumours.     

The changing pattern of neoplastic disease in Canadian Eskimos.

The records of the two main referral centres for the western and central Arctic were reviewed for Eskimo patients with cancer diagnosed between 1949 and 1974 inclusive. To these were added the records for the past 6 years of patients from the eastern Arctic, giving the toatal of 180 histologically proved cases of malignant disease. Athe data were analysed for prevalence, relative frequency, geographic distribution and changes with time of the various neoplasms. Salivary gland and renal neoplasms have in recent years been displaced by cancer of the lung and uterine cervix as the most common malignant tumours in Canadian Eskimos. The prevalence of lung cancer in Eskimo women, particularly of the central Artic, is striking. Cancer of the nasopharynx kept the same relative position during early and late years of the survey period. Breast cancer is still uncommon in Eskimos. Lactation rather than gestation history appeared to be an important protective factor. Cases of cervical cancer outnumbered those of breast cancer by 18 to 4, in sharp contrast to the relative proportions of these tumours in all Canadian women.     

Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours.

To examine the possibility that cytotoxic drugs may cause sterility or congenital malformations in the offspring of women of childbearing age who are cured of cancer a study was conducted of the obstetric histories of 445 long term survivors treated in this unit with chemotherapy for gestational trophoblastic tumours between 1958 and 1978. After completing treatment 97% of those who wished for a pregnancy (49% of all women studied) conceived and 86% had at least one live birth. All these women had received methotrexate. Of the 47 women who wished to conceive and whose combination therapy included cyclophosphamide, 37 (79%) had a live birth. Women who received three or more drugs were less likely to have a live birth than those who received methotrexate alone or with only one other drug (p less than 0.001). There was no statistically significant excess of congenital malformations. These results are strong evidence that the cytotoxic drug regimens used in this unit for treating gestational trophoblastic tumours are compatible with the preservation of fertility in most women and not associated with any increase in congenital abnormalities.     

Contents of putrescine, spermidine and spermine in tissue of the human brain glial tumors

It is shown that in the tissue of the human brain glial tumours the content of putrescine depends on the degree of the tumour malignization. In malignant gliomas (glioblastomas), as compared to the benign (astrocytomas), the content of putrescine is significantly higher. The content of spermidine in glial tumours of a malignancy different degree is twice as high as the level of this polyamine in the brain grey matter, and it is twice as low as in the white matter. The content of spermine in the brain glial tumours does not differ essentially from its level in the brain tissue.