The efficacy of audiotapes in promoting psychological well-being in cancer patients: a randomised, controlled trial.

Open or uncontrolled studies have suggested that providing cancer patients with audiotapes of their clinical interviews can improve information recall and reduce psychological distress. We tested these hypotheses in a ''clinician-blind'', prospective, randomised controlled trial. A total of 117 patients newly referred to a medical oncology clinic who were to be given ''bad news'' had their consultations audiotaped. Blind to the clinician, patients were randomly allocated to receive a copy of the tape to play at home or not (control group). At 6 months follow-up, tape group patients reported positive attitudes to the audiotape and were shown to recall significantly more information about their illness than did controls. Overall improvement in psychological distress at 1 and 6 months follow-up, as measured with the 30-item General Health Questionnaire and the Hospital Anxiety and Depression Scale was no different in the two groups. However, a second-order interaction suggested that poor-prognosis patients were disadvantaged specifically by access to the audiotape, with less improvement in psychological distress at 6 months follow-up than non-tape controls. Patient access to audiotapes of clinical interviews promotes factual retention but does not reliably reduce psychological distress and may be actively unhelpful in some subgroups of patients.     

Differential expression profiling of head and neck squamous carcinoma: significance in their phenotypic and biological classification

The genetic events associated with the development and progression of head and neck squamous carcinoma (HNSC) are largely unknown. We analysed 12 matched pairs of histologically normal squamous mucosa and tumor specimens from six conventional and six phenotypic variants HNSC to define the differentially expressed genes in these tumors. Parallel expression analysis of 8055 unique genes was performed, and the level of the hybridization signal for each gene was measured after normalization. Hierarchical cluster analysis of the expressed genes showed distinct inter- and intra-tumoral patterns in and between conventional squamous carcinoma and squamous carcinoma variants. We also identified 26 (0.32%) differentially expressed genes that were consistently different between matched pairs of normal and tumor specimens; a selected set of the overexpressed genes was validated using real-time quantitative RT-PCR. The majority of the genes were associated with differentiation and proliferation. Our study defines a set of genes that could form the basis for the construction of limited HNSC targeted expression array and in-depth studies and further highlights gene profile differences that may be useful in pathobiologic classification of HNSC.     

Endocrine-responsive breast cancer and strategies for combating resistance

Deaths from breast cancer have fallen markedly over the past decade due, in part, to the use of endocrine agents that reduce the levels of circulating oestrogens or compete with oestrogen for binding to its receptor. However, many breast tumours either fail to respond or become resistant to endocrine therapies. By understanding the mechanisms that underlie this resistance, we might be able to develop strategies for overcoming or bypassing it.     

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.     

Long-term follow-up of a randomised trial designed to determine the need for irradiation following conservative surgery for the treatment of invasive breast cancer.

Four hundred consecutive patients aged under 70 years diagnosed with a clinical T1 or T2 breast cancer were randomised to receive post-operative radiotherapy (n = 208) or not (n = 192), and monitored to record all local recurrences, distant recurrences and deaths for up to 20 years (median 13.7 years). All patients were treated by wide local excision and adjuvant therapy [estrogen receptor (ER) positive: tamoxifen; ER negative: CMF chemotherapy]. Kaplan-Meier and log-rank test methods were used to estimate and compare survival and recurrence. The 20-year Kaplan-Meier rates for local breast recurrence were 28.6% [95% confidence interval (CI) 19.6% to 37.6%] for radiotherapy and 49.8% (95% CI 40.8% to 58.9%). There was no significant difference between the two groups with regard to disease-free or overall survival. The hazard ratio for death among women who received radiation, as compared with those that did not, was 0.91 (95% CI 0.64-1.28; P = 0.59). Therefore, post-operative radiotherapy produced a clear-cut reduction in locoregional recurrence 0.45 (0.31-0.64; P = 0.0001), but did not influence the incidence of distant metastases or time of death. However, of the 119 patients who had a local recurrence, 51 (42.8%) had a distant recurrence, whereas of the 281 without local recurrence only 59 (21%) ever had a distant recurrence. A Cox's regression analysis with local recurrence as a time-dependent variable showed a risk ratio of 5.28 (P < 0.0001). This strong relationship is dependent on the intensity of post-treatment follow-up and investigation.     

Open comparative trial of formestane versus megestrol acetate in postmenopausal patients with advanced breast cancer previously treated with tamoxifen

The aim of the trial was to compare efficacy and safety of the aromatase inhibitor formestane (250 mg i.m. given every 2 weeks) with the progestin megestrol acetate (160 mg administered orally once daily), as second-line therapy in postmenopausal patients with advanced breast cancer previously treated with tamoxifen. A total of 547 patients were enrolled. Analyses revealed no statistically significant or clinically relevant difference between treatments with respect to time endpoints. In the intent-to-treat analysis, the median values for time to failure and overall survival for formestane were 169 and 561 days, respectively. The corresponding values for megestrol acetate were 169 days and 597 days, respectively. Overall response rates were comparable for formestane and megestrol acetate (16.3% vs 20.3%). Formestane was better tolerated than megestrol acetate. In the megestrol acetate group, cardiovascular events, weight increase, and vaginal haemorrhage were significantly more frequent than in the formestane group. Thus, formestane is a suitable alternative to progestins in patients previously treated with tamoxifen.     

Immunohistochemical localisation of pS2 protein in ductal carcinoma in situ and benign lesions of the breast.

The expression of pS2 was examined histochemically in paraffin sections taken from biopsy material from patients diagnosed with ductal carcinoma in situ (DCIS). Often intense immunoreactivity, to an anti-pS2 monoclonal antibody, was observed in comedo, solid, cribriform and micropapillary types of DCIS, with significant positivity found in 63-67% of cases. In 15 samples analysed, we found a good correlation between pS2 expression and presence of progesterone receptor positive cells, but not with estrogen receptor. There was only a limited degree of correspondence between the cells staining with these anti-sera. Some pS2 positive cells were also seen in normal acini in areas adjacent to cancer but much less frequently in sections of normal breast from reduction mammoplasty. Most normal areas were negative, as were cysts. In benign proliferative conditions (seen in sections with and without DCIS) such as adenosis, sclerosing adenosis, mild and florid ductal epithelial hyperplasia, significant pS2 positivity was seen in about 50% of cases. These results suggest that there is a progressive increase in pS2 from normal to benign to cancer cells and that this gene is expressed in both the invasive and pre-invasive forms of breast cancer.     

Clinical management. Sexual frustration

West Hull PCT has set up a joint sexual health an GUM clinic, echoing the inter-disciplinary principles outlined in the public health white paper. Other PCTs have found blurred skill boundaries and training problems to be huge barriers to the policy. Some trusts are "not even close" to meeting the DoH's 48-hour GUM access target by the 2008 deadline.