Role of Doppler ultrasound flowmetry in the diagnosis of breast lumps

One hundred and five patients with discrete breast lumps were examined with a 10 MHz Doppler ultrasonic flowmeter. Doppler flow signals were analysed on an Angioscan spectrum analyser. Recordings from the opposite normal breast were taken as controls and signals from the two sides compared. In 23 patients signals from the normal breast could not be recorded and therefore results of the remaining 82 patients are reported. These included 39 patients with carcinoma, 20 with fibroadenoma, 12 with cyclical nodularity and 11 with cysts. Malignant lumps exhibited significantly higher peak systolic (S) and minimum diastolic frequencies (D) in comparison to the control breast. Fibroadenoma also had a higher S and D than those of the opposite normal breast. Signals over cysts and cyclical nodularity showed no significant difference from the recordings over the control side. Despite significantly higher systolic and diastolic frequencies in the cancer group in comparison to benign lumps and normal breast, considerable overlap in the values was seen between cancer and other groups. Therefore the patterns on 10 MHz Doppler sonography are not sufficiently specific to discriminate benign from malignant breast lumps.     

Organization and expression of human telomere repeat binding factor genes

The ends of mammalian chromosomes terminate in structures called telomeres. Recently a human telomere repeat binding factor (TRF1) that binds the vertebrate TTAGGG telomeric repeat in situ was isolated by Chong et al. (1). TRF1 regulates telomere length (2), which is often altered in cancer cells. To understand their genetic organization, TRF1 genes were localized to human chromosomes 13 cen, 21cen, and Xq13 by analysis of human monochromosomal hybrids, and by fluorescent in situ hybridization. We also confirmed the recent localization of a human TRF1 gene to chromosome 8, and provide evidence that this locus is alternatively spliced. In contrast to the TRF1 genes on chromosomes 8 and X, the chromosomes 13 and 21 TRF1 genes contained a 60 bp deletion in the coding region. The results suggest that two distinct forms of TRF1 are expressed and that the TRF1 gene family includes at least three pseudogenes whose dispersal in the human genome may have occurred via cDNA intermediates.     

Gamma linolenic acid inhibits tyrosine phosphorylation of focal adhesion kinase and paxillin and tumour cell matrix interaction

Gamma linolenic acid (GLA) is an anti-cancer agent recently reported to inhibit tumour cell-matrix attachment. This study examined the effects of GLA on the adhesion of two tumour cell lines, HT115 (human colon) and MDA MB 231 (human breast), to an extracellular matrix, Matrigel. The action of GLA on focal adhesion kinase(FAK) and paxillin was also investigated. Following cell adhesion to Matrigel in control experiments, both FAK and paxillin were quickly tyrosine phosphorylated and become concentrated at focal adhesion areas. Inclusion of GLA resulted in an inhibition of the tyrosine phosphorylation of both FAK and paxillin leading to a reduced attachment of both cell types to Matrigel. FAK and paxillin were also less well distributed in the focal adhesions compared with the controls. It is concluded, therefore, that GLA inhibits tumour-matrix adhesion via the inhibition of FAK and paxillin tyrosine phosphorylation.     

Inhibition of membrane ruffling and ezrin translocation by gamma linolenic acid

Membrane ruffling of a tumour cell is correlated with its motile and metastatic behaviour. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer agent, on HGF/SF induced membrane ruffling in the human cancer cell line, HT115. HGF induced a rapid appearance of membrane ruffling which was related to increased motility and the tyrosine phosphorylation and translocation of ezrin, a membrane-cytoskeleton linker protein. The presence of GLA significantly inhibited both the membrane ruffling and cell motility of the tumour cells, at sub-toxic concentrations. Western blotting revealed that the tyrosine phosphorylation of ezrin was inhibited by GLA. The translocation ezrin from cytosol and generalised areas of cell membrane to ruffled areas of the membrane induced by HGF/SF was also inhibited as shown by both indirect immunofluorescence and transmission electron microscopy. It is concluded that GLA inhibits HGF/SF induced membrane ruffling via its effect on ezrin, and this provides a further molecular explanation for the anti-tumour action of GLA.     

Mastalgia: psychoneurosis or organic disease?

To test the traditional surgical view that pain in the breast is largely an expression of psychoneurosis, the Middelesex Hospital Questionnaire was given to 317 women with mastalgia and 170 controls with varicose veins. Their scores were compared with those of 173 women psychiatric outpatients tested by the designers of the questionnaire. The results were broadly similar in the mastalgia and varicose veins groups, and where there were significant differences women with varicose veins had a higher psychoneurotic score in each case. Within the mastalgia group no difference in scores was observed between patients with cyclical mastalgia and those with mastalgia due to periductal mastitis. Both groups of surgical outpatients had significantly lower scores in major traits than the psychiatric group, except for a small group of patients with breast pain who persistently failed to respond to treatment. Patients with mastalgia are therefore no more "neurotic" than those with varicose veins, and differ greatly from patients with recognized psychoneurosis. Most patients have a physiological or pathological basis for their breast pain, and they deserve an appropriate diagnostic and therapeutic approach.     

A randomized trial of specialist genetic assessment: psychological impact on women at different levels of familial breast cancer risk

The aim was to compare the psychological impact of a multidisciplinary specialist genetics service with surgical provision in women at high risk and those at lower risk of familial breast cancer. Women (n=735) were randomized to a surgical consultation with (trial group) or without (control group) specialist genetic risk assessment and the possible offer of presymptomatic genetic testing. Participants completed questionnaires before and immediately after the consultation to assess anxiety, cancer worry, perceived risk, interest in genetic testing and satisfaction. Responses of subgroups of women stratified by clinicians as low, moderate, or high risk were analyzed. There were no significant main effects of study intervention on any outcome variable. Regardless of risk information, there was a statistically significant reduction in state anxiety (P<0.001). Reductions in cancer worry and perceived risk were significant for women at low or moderate risk (P<0.001) but not those at high risk, and satisfaction was significantly lower in the high risk group (P<0.001). In high risk women who received specialist genetic input, there was a marginally significant trend towards increased perceived risk. The effect of risk information on interest in genetic testing was not significant. Breast care specialists other than geneticists might provide assessments of breast cancer risk, reassuring women at reduced risk and targeting those at high risk for specialist genetic counselling and testing services. These findings are discussed in relation to the existing UK Calman-Hine model of service delivery in cancer genetics. DOI: 10.1038/sj/bjc/6600051 www.bjcancer.comCopyright 2002 The Cancer Research Campaign     

From PCR to RCA: a surgical trainee's guide to the techniques of genetic amplification.

With the advent of evidence-based medicine and the Calman-Hine Report, more and more surgical trainees are undertaking a period of research, either before entering or during their Specialist Registrar training. Many will encounter concepts in science uncommon in daily clinical settings. This paper will elucidate the techniques of genetic amplification available today with their potential for usage in clinical research.     

History, present status and future of sentinel node biopsy in breast cancer. The Mary Béves Lecture

The word 'Sentinel' is defined in The Oxford English Dictionary as 'a guard, one who keeps watch or a sentry'. When translated to the concept of a tumour and its lymph node drainage, the sentinel node could be interpreted to mean the lymph node that guards or keeps watch over a tumour. The sentinel lymph node can thus be defined as the first lymph node that drains a primary tumour within the regional lymphatic basin of that tumour. We know that tumour progression in breast cancer often occurs in an orderly, progressive fashion 12. So in theory, if the sentinel node is tumour free then the rest of the nodes in the lymphatic basin should also be uninvolved by the tumour.