Chromosomal radiosensitivity in G2-phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics.

A substantial proportion of women with breast cancer exhibit an abnormally high radiosensitivity as measured by the frequency of chromatid breaks induced in G2-phase, PHA stimulated lymphocytes. Chromatid break frequencies were compared for a cohort of previously untreated sporadic breast cancer patients and hospital outpatient controls. In the breast cancer group 46% showed high radiosensitivity compared to 14% of controls (P< 0.001). Comparison of those breast cancer patients with a high G2 radiosensitivity (G2RS) versus those with a low G2RS showed no difference in menopausal status or age but the high G2RS group had on average a lower score on the Nottingham Prognostic Index. Predicted survival in the high G2RS group at 15 years was 55% compared to 36% for the low G2RS group. Furthermore, 81% of tumours from the high G2RS were oestrogen receptor positive compared to 45% from the low G2RS group. Thus high G2RS identifies a sub-population of patients with distinctive tumour characteristics and with a predicted improved prognosis as compared with those in the low G2RS group. Our findings imply that besides influencing risk of breast cancer the genetic factors determining G2 radiosensitivity also influence the tumour characteristics and prognosis in these patients.

Educational benefits of student self-marking of short-answer questions.

A pilot study was undertaken to evaluate the feasibility and reliability of undergraduate medical student selfmarking of degree written examinations, and to survey student opinion regarding the process. The correlation between student and faculty staff scores for individual questions and the total examination was high (correlation coefficient ranged from 0.77 to 0.91: p < 0.001). There were no significant differences between the mean student and mean faculty staff scores for individual questions or the total examination: 98% (97199) of student scores fell within ± 15% of the faculty staff score, with 92% (91199) of students falling within ± 10%. Although the approach was demonstrated to be reliable, students generally failed to acknowledge the potential value of self-marking in terms of feedback and as a learning opponunity, and found the process stressful.

Twelve tips for setting up an ambulatory care (outpatient) teaching centre.

The ambulatory care setting is becoming an increasingly important environment for clinical teaching. This reflects the changing focus of healthcare delivery with more procedures and patient treatment being delivered in this setting. Maximizing learning opportunities for students without compromising patient care has never provided a greater challenge. This paper shares 12 educational tips for developing an ambulatory care teaching centre where both students and patients benefit from a protected yet realistic clinical setting.

Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery.

Antibiotic prophylaxis has been used to good effect in the prevention of post-operative wound infections in patients undergoing gastrointestinal operations. We have assessed the use of a single dose of intravenous antibiotic (Augmentin 1.2 g), given with induction of anaesthesia as prophylaxis, against post-operative wound infection in women undergoing clean, elective breast surgery. Three hundred and thirty-four patients were recruited. Of the 164 receiving antibiotic prophylaxis 29 (17.7%) had wound infections compared with 32 (18.8%) in the placebo group (P=0.79). There were no significant differences in any other post-operative infective complications. Antibiotic prophylaxis is probably not required in clean, elective breast surgery.

Shared teaching in health care ethics: a report on the beginning of an idea.

In the majority of academic institutions nursing and medical students receive a traditional education, the content of which tends to be specific to their future roles as health care professionals. In essence, each curriculum design is independent of each course. Over the last decade, however, interest has been accumulating in relation to interprofessional and multi-professional learning at student level. With the view that learning together during their student training would not only encourage and strengthen future collaboration in practice settings but also enhance patient care, the University of Dundee decided to run a pilot study to explore shared teaching in ethics between medical and nursing students. This article presents a report on the reasons for selecting health care ethics as a precursor for shared teaching, the educational tool used for the sessions, and the results of student and facilitator evaluation of the short course. Overall, despite problems such as poor attendance by some students, and facilitation and timetable difficulties, most of the feedback from students and facilitators has been positive. In essence the 'idea' has gone from strength to strength and there are now three levels of shared teaching in ethics between nursing and medical students, with plans to include further sessions with students from other disciplines. Within the text, 'health care ethics' will be referred to as 'ethics'; nursing students/nurses encompasses midwifery students/midwives.

The modified B-mammoplasty incision: an alternative skin-conserving technique for mastectomy with immediate breast reconstruction.

A modification of the B-mammoplasty incision (originally described by Regnault for reduction mammoplasty) is presented for patients undergoing skin-conserving mastectomy and reconstruction. This approach has several advantages; not only does it facilitate good exposure for the oncological surgeon to carry out the mastectomy, but it can easily be extended into the axilla to allow nodal clearance and microvascular access. It creates a suitable pocket into which a flap can be tailored or implant/expander inserted, and further adjustment of the breast size or shape can be undertaken easily. Most importantly, the scar is confined to the infralateral aspect of the breast, leaving the aesthetically important upper and medial breast skin scar free.

Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity.

Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. Previous attempts to determine chemosensitivity ex vivo have been disappointing, but in this study results from a newly developed tumor chemosensitivity assay (TCA) have been correlated prospectively with patient response. In this study, we have used heterogeneity data for standard regimens obtained from 116 breast TCAs to set sensitivity/resistance thresholds which were then used to interpret the results from those with known clinical responses. Assay evaluability was 97% in surgical biopsies. Clinical follow-up of stage III/ IV assessable disease was obtained from 27 breast tumors which were successfully tested for chemosensitivity, including 13 needle biopsies. The ATP-TCA assay predicted response correctly in 22 out of 29 (76%) tumors with clinically evaluable disease, suggesting that it is capable of predicting outcome in individual patients. Assays were performed in seven patients before and after chemotherapy using residual or recurrent tumor tissue. Four cases with initial sensitivity showed a decrease in sensitivity within 6 months of starting chemotherapy, while two others without clinical resistance were still sensitive by TCA. All nine courses of therapy given on the basis of TCA sensitivity resulted in partial or complete responses. Controlled trials of TCA-directed treatment against standardized empirical therapy should be conducted before this technology is widely adopted to assess its impact on rates of response, survival and the cost of treatment.

Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity.

Many cytotoxic agents act by causing DNA damage, and the p53 tumour suppressor gene is known to be involved in the cellular response to DNA damage. Since inactivation of p53 is common in many tumours, we wondered if this would affect the sensitivity of cancer cells to cytotoxic agents. We have shown that this is indeed the case in transformed mouse cell lines with and without a mutated p53 gene; p53 "knockout" mouse fibroblasts, and normal human skin fibroblasts treated with an anti-sense p53 oligonucleotide. In addition, we have demonstrated a correlation between p53 protein expression in human breast cancer specimens and their chemosensitivity. The results show that inactivation or mutation of p53 renders cells more sensitive to those cytotoxic drugs whose primary mechanism of action is DNA damage.

Heterogeneity of chemosensitivity in human breast carcinoma: use of an adenosine triphosphate (ATP) chemiluminescence assay.

Cancer chemotherapy is currently given to patients with breast carcinoma on the basis of data from response rates in patients with advanced disease, or from the results of clinical trials of adjuvant therapy. However, individual tumours may vary in their response to particular cytotoxic drugs: optimal therapy for a population of patients may not be the correct treatment choice in individual cases. In this study we have used an ATP-based non-clonogenic chemosensitivity assay (TCA-100) to investigate the heterogeneity of chemosensitivity of human breast carcinoma to a number of cytotoxic drugs, both as single agents and in combination. Tissue was obtained from 33 patients. Most samples were excision biopsies, but sufficient tumour cells were obtained from three needle biopsies and three pleural effusions for assays to be performed. The results show wide variation in the response of individual breast tumours to single agents, but most tumours show sensitivity to the commonly used combination regimens. The TCA-100 assay may provide useful information to support the choice of regimen for breast cancer chemotherapy.

Is mammographic microcalcification of biological significance?

Mammographic microcalcification is a feature of a proportion of breast cancers. Its occurrence does not appear to be significantly associated with age or primary tumour size. Lymph node involvement by tumour is present in 50% of patients with mammographic microcalcification in relation to the primary tumour, but only 24% of patients without microcalcification. A significantly larger number of lymph nodes (61 of 241 nodes) are involved with tumour in patients with, in comparison to those without (59 of 476 nodes) microcalcification (P < 0.001, chi 2 test). These differences suggest a biologically significant role for the deposition of calcium in microcalcifications, which may relate to the process of tumour cell metastasis. This may be of importance in the assessment of patients with cancers which demonstrate microcalcification on mammography.

Tamoxifen metabolism is altered by simultaneous administration of medroxyprogesterone acetate in breast cancer patients.

We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period. We suggest that the interaction between these drugs may involve additional sites (probably hepatic) besides the desired target tumour.

Effects of fine needle aspiration on subsequent mammograms.

The effects of fine needle aspiration on subsequent mammography were studied in a group of women who were referred with palpable breast lumps. Fifty-two women aged between 36 and 73 (median 53) years underwent mammography before and within 5 days of needle aspiration. Preaspiration and postaspiration mammograms were examined 'blind' by one radiologist. In ten cases, a difference was seen between the preaspiration and postaspiration films. In seven (aged 36-50 years) this was due to aspirated cysts. In three the differences were unexpected and were more significant, although the radiological diagnosis was not altered. If this proportion is extrapolated for a large number of patients then significant numbers of artifacts from fine needle aspiration might be seen on mammograms. It is possible that some might be interpreted falsely as malignant and some small cancers might be obscured. Women accepted mammography more readily before aspiration than after.

Pyridinium crosslinks as markers of bone resorption in patients with breast cancer.

Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.

Potential use of tumour marker CA 15-3 in the staging and prognosis of patients with breast cancer.

The tumour marker CA 15-3 has been assayed in 130 patients with breast cancer and correlated with stage of their disease at presentation. The median value of CA 15-3 (43 kU/l) in 26 patients with stage IV disease was significantly higher than the median for 97 patients classified as stage I or II (17 kU/l). Values were elevated in 18 of 21 (86%) patients with bone metastases at presentation. For the 41 patients with stage I or II disease presenting with levels of CA 15-3 of greater than 20 kU/l, the disease-free interval and survival were significantly less than for 56 patients presenting with levels of less than 20 kU/l. CA 15-3 provides additional information to conventional staging tests for patients presenting with breast cancer and may also have a role as a prognostic indicator. This may be particularly useful in the selection of patients for neoadjuvant therapy.

Patterns of presentation of breast disease over ten years in a specialised clinic.

A clinic specialising in breast disease has been surveyed over a decade. Detailed information has been collected on 3,500 women with benign breast disorders and 950 with breast cancer. Over this time, the demand for and utilisation of this facility has increased steadily. Over the ten years, there has been a trend for a higher proportion of breast cancers to be smaller in size and for fewer cancers to be locally advanced or metastatic at presentation. Critical appraisal of referral and consultation patterns indicates that the original aims of establishing this clinic have not been maintained. Paradoxically, this is a result of the success of the exercise. Measures which might lead to a higher proportion of patients with breast cancer being managed at the Breast Clinic rather than a General Surgical Outpatient Clinic are discussed.

Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only.

One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy.