Search Results - (Author, Cooperation:T. Powles)

2014-11-28

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Antigens, CD274/metabolism ; Female ; Humans ; *Immunotherapy ; Male ; Middle Aged ; Treatment Outcome ; Urinary Bladder Neoplasms/*therapy

1749-6632

Blackwell Publishing Journal Backfiles 1879-2005

Natural Sciences in General

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] The addition of collagenase to tissue culture medium bathing 45Ca-labelled neonatal mouse calvaria increases their release of 45Ca (Table 1) and results in macroscopically obvious disruption of the calcified matrix, together with connective tissue lysis involving the fronto?parietal suture line and ...

Electronic Resource

0960-0760

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Electronic Resource

1569-8041

breast cancer ; chemotherapy ; mastectomy ; neoadjuvant ; tamoxifen

Springer Online Journal Archives 1860-2000

Medicine

Abstract Backgound: A prospective randomised trial was undertaken to evaluate the role of neoadjuvant chemoendocrine therapy prior to surgery in primary operable breast cancer. Patients and methods: Three hundred nine women (median age 56 years, range 27–70) with primary operable breast cancer confirmed on fine needle aspiration (FNA) cytology were recruited to this study. They were treated with a combination of mitozantrone and methotrexate (± mitomycin-C) combined with tamoxifen (2MT). Patients received eight cycles of 2MT (four prior to surgery in the neoadjuvant group) and tamoxifen for five years with appropriate surgery and radiotherapy. The two groups were comparable for age, menopausal status, stage and surgical requirements. Results: The clinical response rates to neoadjuvant therapy were as follows: 22% complete response (CR), 29% minimal residual disease (MRD), 33% partial response (PR), 15% no change (NC) and only two patients had clinical evidence of progressive disease. Surgical requirements were reduced from 31 patients (22%) of the adjuvant group having mastectomy to 14 (10%) in the neoadjuvant group (P 〈 0.003). At a median follow-up of 48 months (range 10–70 months) there is no statistically significant difference between the two groups in terms of local relapse, metastatic relapse or overall survival. Symptomatic and haematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. Conclusion: This randomised trial has shown a significant reduction in the surgical requirements for mastectomy, after treatment with neoadjuvant chemoendocrine therapy, with no deterioration in local or distal relapse.

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1569-8041

breast cancer ; chemotherapy ; margins ; radiotherapy

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin. Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.

Electronic Resource

1432-2307

Fine needle aspiration ; Breast cancer ; Immunocytochemistry ; Cytospin technique ; Flow cytometry

Springer Online Journal Archives 1860-2000

Medicine

Abstract The increasing use of neoadjuvant chemotherapy and endocrine therapy in the management of breast cancer has lead us to evaluate and optimise the standard technique of cytocentrifugation of a single fine needle aspirate (FNA) taken from a breast tumour in-vivo, to determine a range of both immunocytochemical and flow cytometric factors which are predictive of response to primary medical therapy. Some of these factors are also of prognostic significance in early stage disease. An analysis of the cellularity and immunocytochemical staining characteristics of FNAs obtained from a series of 206 patients with palpable breast cancers indicate that in a sample of 46 cases it is possible to measure oestrogen receptor, progesterone receptor and c-erbB-2 providing over 400 cells per slide are obtained, with material obtained in a single FNA prepared by cytocentrifugation, using standard immunocytochemical methods. The staining results obtained were comparable to those obtained using frozen or paraffin embedded tissue sections taken from the same tumour. In addition an estimate of the proliferation indices could be made by flow cytometric analysis of the residual cell suspension fluid with measurement of DNA index and S-phase fraction in 131/164 (80%) and 110/164 (67%) of cases respectively. Providing all FNAs obtained for cytocentrifugation were taken at first presentation rather than immediately following a standard FNA, then it was possible to obtain adequately cellular (〉400 cells/slide) samples in 96 out of 126 (75%) of the last cohort of breast aspirates. These effects may be independent of T stage but not histological type as patients with lobular tumours only produced cellular aspirates in 1/7 (14%) of cases. The advantages and disadvantages of using FNA over trucut biopsy are discussed further.

Electronic Resource

1432-0843

Breast cancer ; Aromatase inhibitors ; 4OHA

Springer Online Journal Archives 1860-2000

Medicine

Abstract This study investigated the influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E 2) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E2 was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3%±9.5%, 70.0%±5.1% and 57.3%±5.3%, respectively (mean±SEM). Corresponding values for plasma E2 suppression were 30.7%±6.5%, 43.4%±4.5% and 42.9%±6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E2 levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E2 suppression was observed. The suppression of E2 by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary Repeated administration of long-acting analogues of gonadotrophin-releasing hormone down-regulates the pituitary gonadotrophins and gonadal hormones. The activity of these compounds in premenopausal women with breast cancer has been previously noted. In an attempt to cause a highly selective medical hypophysectomy 18 consecutive postmenopausal women with symptomatic advanced breast cancer were treated with intranasal buserelin in divided dosages of either 600 or 1000 μg daily. The pituitary gonadotrophins were suppressed in all patients, without objective evidence of response. This is in contrast with an earlier finding that the long-acting analogues of gonadotrophin-releasing hormone were effective in postmenopausal patients with breast cancer.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary Aspirin and indomethacin, flurbiprofen, synthetic human calcitonin, and mithramycin were assessed for their anti-osteolytic properties in patients with breast cancer and painful skeletal metastases. Some patients responded with pain relief to aspirin/indomethacin (2/10), flurbiprofen (2/9), calcitonin (2/7), and mithramycin (3/8). Objective evidence of reduction of osteolysis occurred with flurbiprofen, mithramycin, and calcitonin, but not with aspirin and indomethacin. A sustained reduction in hydroxyproline occurred with flurbiprofen (2/8) and mithramycin (2/8). A reduction of hypercalcaemia occurred with flurbiprofen (2/4), calcitonin (1/1), and mithramycin (2/4). These findings indicate that these agents have no place as primary therapeutic agents for osteolytic bone metastases but they may be useful as an adjuvant to other therapy.

Electronic Resource

1432-0843

Key words Breast cancer ; Aromatase inhibitors ; 4OHA

Springer Online Journal Archives 1860-2000

Medicine

Abstract  This study investigated the influence of the aro- matase inhibitor 4-hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E 2) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E2 was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3%±9.5%, 70.0%±5.1% and 57.3%±5.3%, respectively (mean±SEM). Corresponding values for plasma E2 suppression were 30.7%±6.5%, 43.4%±4.5% and 42.9%±6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E2 levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E2 suppression was observed. The suppression of E2 by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary Fifty-seven patients with metastatic breast carcinoma have been treated with mitomycin C (10 mg/m2 IV 6-weekly), melphalan (6 mg/m2 POx3 days, 3-weekly), and methotrexate (35 mg/m2 IV 3-weekly) to assess the efficacy and toxicity of this regimen. Of 48 evaluable patients 19 (40%) responded for a median period of 5 months and 12 (25%) had stabilisation of disease. Of the 12 patients previously treated with adriamycin only one responded, whereas 18 of the 36 patients without previous chemotherapy responded. Although healing of bone metastases was infrequent control of hypercalcaemia was commonly seen. Generally the treatment was well tolerated and treatment was stopped in only five patients because of toxicity. Cummulative marrow toxicity was observed but was not a significant problem in the first 6 months of treatment. Mitomycin C, melphalan, and methotrexate (MMM) appears to provide an effective, well tolerated chemotherapy combination for metastatic breast carcinoma.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary To assess the modulating effects of a non-steroidal anti-inflammatory drug on chemotherapeutic agents, 183 patients with advanced breast cancer have been treated in a randomised study with flurbiprofen or placebo and adriamycin plus a vinca alkaloid. To assess the efficacy of the new vinca alkaloid, vindesine, in breast cancer, patients were further randomised to receive vindesine or vincristine. The overall response rate in evaluable patients was 57%, and the median duration of response in the different treatment groups varied from 6 to 10 months. Response rates and toxicity in vindesine- and vincristinetreated patients were similar, although with vindesine neurotoxicity was slightly lower. Flurbiprofen did not improve the response rate or reduce the toxicity of adriamycin plus vinca alkaloid.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary A phase-II study of vindesine was carried out in 23 patients with histologically proven advanced breast carcinoma. Toxicity was assessed in a further 24 patients with several different tumour tupes. Treatment was given in a starting dose of 3 mg/m2 weekly by IV bolus, increasing by 1 mg weekly as toxicity allowed. The response rate in 21 evaluable patients with breast carcinoma was 29%. In 47 patients evaluable for toxicity, leukopaenia occurred in 45% and was doserelated; thrombocytopaenia was rare (4%); neurotoxicity occurred in 40%; constipation in 17%, alopoecia in 46% and an influenza-like syndrome in 21%. It was concluded that vindesine was a clinically active agent in breast carcinoma, with a spectrum of toxicity lying between those of vincristine and vinblastine.

Electronic Resource

1573-7217

aminoglutethimide ; aromatase inhibition ; breast cancer ; 4-hydroxyandrostenedione ; oestrogen ; oestrone sulphate

Springer Online Journal Archives 1860-2000

Medicine

Summary The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p〈0.05). Plasma oestrone was suppressed by a mean of 40.6% (p〈0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p〈0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.

Electronic Resource

1573-7217

biochemical markers ; recurrence ; breast cancer

Springer Online Journal Archives 1860-2000

Medicine

Abstract In 141 postmenopausal node-positive patients with primary breast cancer, routine biochemical markers (alkaline phosphatase, gamma-glutamyl transpeptidase, carcinoembryonic antigen), and chest x-ray, in combination with history and clinical examination, have been performed at 3 monthly intervals for at least 2 years. Sixty one patients relapsed at a median time of 14 months. The recurrence was detected at routine follow-up in 40 (66%) patients. Of these 40 patients, 26 (65%) presented with symptoms, 11 (28%) were asymptomatic but were found to have relapsed on clinical examination, and only 3 (8%) had their relapse diagnosed on the basis of an abnormal chest x-ray. The remaining 21 patients presented early with symptoms. Therefore symptoms and clinical examination accounted for the detection of relapse in 58 of the 61 (95%) patients. Of the patients who had relapsed, 49% (30 of 61) had one or more abnormal markers/chest x-rays prior to relapse, rising to 79% (48 of 61) at the time of relapse. Of 80 patients with no evidence of recurrence, 36% (29) had no marker abnormality recorded, whereas in 64% (51) one or more abnormalities were found. These results suggest that history and examination are the important procedures in follow-up, and that abnormal markers are not always due to metastatic disease and may be misleading.

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1573-7217

chemoprevention ; compliance ; tamoxifen ; toxicity

Springer Online Journal Archives 1860-2000

Medicine

Abstract A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been undertaken in order to evaluate the problems of accrual, acute symptomatic toxicity, compliance, and safety as a basis for subsequent large national multicentre trials designed to test whether tamoxifen can chemoprevent breast cancer. From October 1986 until June 1993, 2012 healthy women with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxifen 20 mgs/day or placebo for up to 8 years if possible. Accrual remained high in spite of extensive informed consent regarding potential risk. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medication at 5 years. There was a significant increase in hot flushes (34% versus 20%) mostly in premenopausal women (p 〈 0.005), vaginal discharge (16% versus 4%, p 〈 0.005), and menstrual irregularities (14% versus 9%, p 〈 0.005). The requirements for hormone replacement therapy for women on tamoxifen or placebo were the same. Safety monitoring indicates no adverse anti oestrogenic effects of tamoxifen. There was no obvious effect of tamoxifen on bone mineral densities (single photon radial absorption). The fibrinogen and antithrombin III were both lowered, resulting in no observed detrimental effect on the ratio of these clotting factors. There was a significant reduction in the serum cholesterol maintained out to 5 years. Annual pelvic assessment using transvaginal ultrasound indicates an increased incidence of uterine fibromata and benign ovarian cysts. These results have encouraged the commencement of the NSABP national trial in the USA, and the subsequent start of national trials in Italy and the UK, which together should provide sufficient evidence to evaluate the efficacy of tamoxifen for prevention of breast cancer.

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