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Biomedical subjects

J A Dewar

Publications and source records attributed to J A Dewar.

At least 19 recordsLinked to original sources
PubMed2006

Postmastectomy radiotherapy.

Radiotherapy given after mastectomy (PMRT) will reduce the risk of local recurrence by about two-thirds. The absolute benefit will depend on the risk of local recurrence, which will depend on pathological characteristics (tumour size, nodal status, etc.) but also the type and extent of the surgery. The overall effect of radiotherapy on survival has changed with time. Improved local control reduces the risk of dying from breast caner, presumably by preventing secondary dissemination from recurrent disease. Older radiotherapy techniques were associated with an excess risk of cardiovascular death, which counterbalanced the improvement in survival seen with better local control. More recent studies show that modern radiotherapy techniques can improve local control and avoid cardiac morbidity. PMRT remains an important component of the management of patients with breast cancer.

Breast Neoplasms↗
PubMed2004

Improvements in survival for women with breast cancer in Scotland between 1987 and 1993: impact of earlier diagnosis and changes in treatment.

We investigated changes in survival, and their causes, in women with early breast cancer diagnosed in Scotland. The Scottish Cancer Registry identified 1617 and 2077 such women, without metastases at diagnosis who underwent surgery as part of their primary treatment, diagnosed in 1987 and 1993, respectively. There was a statistically significant 11% improvement in 8-year survival between 1987 and 1993. Survival improved across almost all clinical/pathological, treatment and health care delivery/deprivation categories; improvement was not limited to those women diagnosed through the screening programme. In a multivariate model, improved survival appeared to be explained largely by screening and clinical/pathological prognostic factors. Deprivation also had an adverse effect on survival; however, the geographical variation in survival observed for women diagnosed in 1987 was not apparent by 1993. We did not demonstrate a significant independent effect of surgical caseload on survival. We conclude that survival has increased partly as a consequence of screening and earlier diagnosis, but also due to improvements in the organisation and delivery of care.

Adult↗
PubMed2002

Tamoxifen beyond 5 years--patients' decisions regarding entry to the aTTom trial.

The aim of this study was to assess among a population of women who had taken adjuvant tamoxifen for 5 years, how many were prepared to enter a randomised trial looking at the duration of tamoxifen treatment and what was the preference of those who declined trial entry. There is uncertainty as to the optimum duration of adjuvant tamoxifen and this is the subject of the aTTom (adjuvant Tamoxifen Treatment offer more?) trial in which patients are randomised to continue or stop tamoxifen after 5 years. Patients have been recruited to the aTTom trial in Dundee since 1996 and a record has been kept of all the patients with whom the trial was discussed. Patients who declined trial entry were allowed to choose whether to electively stop or continue tamoxifen. 306 patients were eligible for trial entry of whom 171 (56%) consented to randomisation (82 to continue and 89 to stop). Amongst the 135 (44%) who declined randomisation, 28 (21%) elected to stop tamoxifen treatment, 90 (67%) elected to continue and in 17 (13%) their decision was unclear. These results illustrate that patients eligible for the aTTom trial share our clinical equipoise. A majority (56%) of patients were agreeable to randomisation, but among those who declined, some (67%) preferred to continue, some (21%) to stop tamoxifen. This trial is unusual in that the patients have already experienced the treatment options, so the patients' preferences reflect a truly informed choice.

Antineoplastic Agents, Hormonal↗
PubMed1999

Megestrol acetate therapy and secondary adrenal suppression.

BACKGROUND: Adrenal suppression has been noted in patients who are receiving medroxyprogesterone acetate (MPA). Megestrol acetate (MA) is used to treat patients with advanced breast carcinoma, cachaexia related to acquired immune deficiency syndrome, and disseminated carcinomatosis, and it is believed to have fewer side effects than MPA. The aim of this study was to test for secondary adrenal suppression in patients receiving MA therapy for advanced metastatic cancer. METHODS: Ten postmenopausal female patients receiving long term MA therapy, nine with advanced metastatic breast carcinoma and one with metastatic ovarian carcinoma, were recruited consecutively from the oncology outpatient clinic at Ninewells Hospital in Dundee, Scotland. A short synacthen test and a corticotrophin-releasing hormone (CRH) stimulation test were performed on two separate occasions. Urine collection for 24-hour urinary free cortisol was performed on 6 patients. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (T4) were measured in eight patients. An insulin stress test (IST) was performed on two patients. RESULTS: Nine of 10 patients had a poor cortisol response to the short synacthen test. The CRH test had abnormal results in eight of nine patients. In all patients tested, 24-hour urinary free cortisol excretion was low, indicating adrenal suppression. Basal serum FSH, LH, TSH, and free T4 values indicated normal pituitary function. Adrenocorticotrophic hormone response in the CRH test varied and is discussed in this article. CONCLUSIONS: MA causes secondary adrenal suppression that is thought to be due to its effect at the hypothalamic level. The authors recommend a short course of steroid replacement for patients receiving MA at times of acute illness.

Adrenal Glands↗
PubMed1999

In pursuit of excellence for patients with cancer: the Scottish Cancer Therapy Network model.

The Scottish Cancer Therapy Network (SCTN) was created against a background of rising concerns about perceived variation in the quality of care available to patients with cancer. SCTN has established itself as a major organization with the necessary recognition and infrastructure to provide leadership, support and impetus in the field of clinical guidelines, clinical audit and clinical trials of cancer therapy in Scotland. Since being formed in 1993, SCTN has been instrumental in the development of three evidence-based, clinical guidelines and in the completion of detailed, national, retrospective audits of the treatment of five major tumour sites. The infrastructure has been used successfully to support and encourage trial participation. Challenges for the future are a re-orientation towards prospective audit, widening the constituency and sense of ownership of SCTN as a resource for practising clinicians, and further increasing recruitment into clinical trials.

Clinical Trials as Topic↗
PubMed1999

Breast cancer in Scotland: changes in treatment and work-load. Scottish Breast Cancer Focus Group and the Scottish Cancer Therapy Network.

Throughout Scotland, the patterns of care of patients with breast cancer were examined for the years 1987 and 1993. Substantial changes in oncological work-load were shown in the intervening period. The number of patients referred to an oncologist (clinical or medical) increased by 52% (from 1076 to 1634), the number of patients receiving postoperative radiotherapy to the breast or chest wall increased by 72% (from 724 to 1248) and the number of patients receiving adjuvant chemotherapy increased by 215% (from 123 to 388). The number of consultant oncologists increased by only 16% (from 32 to 37). If patients are to be treated to the standards expected, then increases in work-load must be matched by appropriate increases in staff.

Breast Neoplasms↗
PubMed1998

Variation in the survival of women with breast cancer in Scotland. The Scottish Breast Cancer Focus Group and The Scottish Cancer Therapy Network.

We have investigated factors influencing the survival of women with early breast cancer in Scotland. In a retrospective study, clinical, treatment and 'service' factors, e.g. surgical case load, deprivation and geographical area (health board of first treatment) were recorded from hospital records. A total of 2148 women with invasive breast cancer diagnosed in 1987 were identified from the Scottish Cancer Registry, of whom 1619 without metastases at diagnosis underwent surgery as part of their primary treatment. In a multivariate analysis, clinical factors (age, clinical stage, pathological tumour size, node status and oestrogen receptor status) all influenced survival. After allowing for these clinical factors, surgical case load and deprivation did not have statistically significant effects on survival. By contrast, health board did affect survival. This was explained in part by the selection of patients for surgery. There appeared, however, to be a residual effect that may be related to differences in the use of adjuvant systemic treatment among the different health boards. We conclude that, in Scotland, geographical variation in both surgical and non-surgical treatment has a greater effect on variability in survival for women with breast cancer than surgical case load and deprivation.

Adult↗
PubMed1996

Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group.

In 1985 a second randomisation was initiated for women in the treatment arm of the Scottish Tamoxifen Trial either to stop tamoxifen at 5 years or to continue indefinitely. A preliminary analysis of outcome in 342 patients at a median follow-up of 6 years suggests that a worthwhile gain in disease control from continuing adjuvant tamoxifen beyond 5 years is unlikely. [Hazard ratio for events (relapse or death without relapse) is 1.27, 95% CI = 0.87 - 1.85.] There is a suggestion that therapy for longer than 5 years may increase the risk of endometrial carcinoma (P = 0.064).

Adult↗
PubMed1996

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (Institut Gustave Roussy 1970-1982). IGR Breast Cancer Group.

BACKGROUND: Breast conservation is now established treatment for patients with small breast cancers. The authors reviewed a large series of patients with long term follow-up who underwent conservative treatment. Clinical and pathologic factors were analyzed to identify patients at an increased risk of relapse in the breast (local relapse) or development of a contralateral tumor. METHODS: Seven hundred fifty-seven patients with unilateral invasive breast cancer (T0-2, N0-1, M0) were treated conservatively (wide local excision and radiotherapy) at the Institut Gustave-Roussy between 1970 and 1982. The median follow-up was 9 years. The risk of local relapse or development of a contralateral tumor (as first event) was studied by univariate analysis for the main clinical, pathologic, and treatment factors. Those found to be significant were entered into a Cox proportional regression analysis. RESULTS: Fifty-one patients relapsed in the treated breast (actuarial local relapse rates at 5 and 10 years were 5% and 8%, respectively) and 34 in the contralateral breast (actuarial contralateral tumor rates at 5 and 10 years were 3% and 6%, respectively). Multivariate analysis of the risk factors for local relapse showed that only age younger than 40 years (P < 0.02) or inadequate surgical excisioin (P < 0.02) were significant. No particular risk factors for contralateral tumor development were identified. CONCLUSIONS: Overall, for most patients, the risk of local relapse or of developing a contralateral tumor was low. A small number of young patients with inadequately excised tumors are at higher risk of local relapse, need more meticulous surgery, and may merit higher dose radiotherapy.

Actuarial Analysis↗
PubMed1993

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.

Adenosine Triphosphate↗