781. |
- Rose, Carsten, et al.
(författare)
-
An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole
- 2003
-
Ingår i: European Journal of Cancer. - 1879-0852. ; 39:16, s. 2318-2327
-
Tidskriftsartikel (refereegranskat)abstract
- It was previously shown that letrozole (Femara(R)) was significantly more potent than anastrozole (Arimidex(R)) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. Letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy. (C) 2003 Elsevier Ltd. All rights reserved.
|
|
782. |
|
|
783. |
- Rosenberg, Per, et al.
(författare)
-
Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum
- 2002
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 41:5, s. 418-424
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly (arm A) or every 3 weeks (arm B), and to assess the safety of intravenous steroids versus standard peroral premedication. Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were randomized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks. The median delivered dose intensity was 77.6 mg/m2/week in the weekly arm, and 72.7 mg/m2/week in the every 3 weeks arm. WHO grade 3-4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity, response rate, time to progression or survival between arms was observed. Weekly paclitaxel at a dose of 67 mg/m2/week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks. Intravenous steroids are a safe alternative to oral steroids.
|
|
784. |
- Rosendahl, Ann, et al.
(författare)
-
Influence of IGF-IR stimulation or blockade on proliferation of human renal cell carcinoma cell lines
- 2004
-
Ingår i: International Journal of Oncology. - 1019-6439. ; 25:5, s. 1327-1336
-
Tidskriftsartikel (refereegranskat)abstract
- Several tumors secrete insulin-like growth factors (IGFs) for autocrine growth stimulation and protection from apoptosis. However, the mechanisms responsible for tumor growth in renal cell carcinoma (RCC) are unclear. In this study the biological role of exogenous IGFs in two malignant RCC cells (Caki-2 and SK-RC-52) were investigated in vitro, and compared to the breast cancer cell line MCF-7. IGFs but not the related epidermal growth factor stimulated both RCC cell lines. Caki-2 expressed higher levels of IGF-IR and proliferated more vigorously to added IGF-I, IGF-I analogues des(1-3)IGF-I, LongR(3)IGF-I and IGF-II compared to SK-RC-52. Neutralizing IGF-IR antibodies reduced the IGF driven proliferation in both cell lines. Interestingly, soluble IGF-I receptor resulted in strong growth inhibition of SK-RC-52, while no marked effect on Caki-2 was observed. Moreover, Caki-2 expressed a broad panel of IGFBPs, while SK-RC-52 more selectively secreted high levels of IGFBP-3. Exogenous IGFBP-3 strongly inhibited IGF-I driven proliferation in SK-RC-52, but worked in synergy with IGF-I in Caki-2. Both the IGF-IR and IGFBP-3 were present in respectively 4/4 and 4/8 human malignant renal tissues. In light of this and with the functional data presented in this study, interference with this growth factor system may provide a novel therapeutic approach in renal cancer therapy.
|
|
785. |
- Rudolph, Pierre, et al.
(författare)
-
Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer
- 2001
-
Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 32:3, s. 311-319
-
Tidskriftsartikel (refereegranskat)abstract
- Simultaneous overexpression of c-erbB-2 and p53 has been reported to be prognostically unfavorable in breast cancer. Herein, we show that concurrent overexpression of these 2 proteins is associated with a marked reduction in the relative fraction of cells in G(1) phase of the cell cycle, indicating an accelerated cell cycle progression. Using an immunohistochemical approach, we examined 261 cases of node-negative infiltrating ductal carcinomas of the breast with respect to c-erbB-2 and p53 expression and to the proliferative activity measured by the Ki-67 index. By means of a novel monoclonal antibody, Ki-S2, which exclusively recognizes proliferating cells in the S, G(2), and M phases of the reproductive cycle, we were further able to calculate the relative fraction of the cells having passed the restriction point at the G(1)/S boundary, thus defining a cycling ratio (CR). The results were correlated with clinical outcome; median follow-up time was 96 months. Tumors that simultaneously overexpressed c-erbB-2 and p53 had a high median CR and followed an unfavorable course. However, increased CRs were also observed independently of c-erbB-2 and p53 overexpression, suggesting that other molecular mechanisms may contribute to acceleration of cell cycle progression. In a multivariate analysis that included patient age, tumor size, hormone receptor status, c-erbB-2 and p53 expression, and the Ki-67 index, CR emerged as the most significant independent predictor of overall and disease-free survival (P <.0001). It is concluded that the CR is a gauge of cell cycle deregulation and therefore may be a powerful indicator of the biologic behavior of cancers.
|
|
786. |
- Rudolph, P, et al.
(författare)
-
Differential prognostic impact of the cyclins E and B in premenopausal and postmenopausal women with lymph node-negative breast cancer
- 2003
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 105:5, s. 674-680
-
Tidskriftsartikel (refereegranskat)abstract
- Searching for new prognostic factors, we investigated the influence of cyclin expression on breast cancer prognosis. A total of 273 archival tumor specimens from patients with pT1/pT2 NO breast cancers treated by surgery and local irradiation were immunostained for cyclins E, A and B. Outcome was evaluated as metastasis-free (MFS) and diseasespecific survival (DSS) over a median observation period of 99 months. In postmenopausal women, DSS was significantly predicted by cyclin E, and in premenopausal patients by cyclin B. No statistical significance was found for cyclin A. When the prognostic impact of cyclins was compared to that of standard prognostic indicators in a multivariate analysis, both cyclin E and cyclin B were selected as independent predictors of survival in postmenopausal and premenopausal patients, respectively. After inclusion of Ki-67 in the model, cyclin E lost its significance, whereas cyclin B remained the only independent prognostic factor with a hazard ratio of 4.5 (p = 0.026) for tumor-related death. Assessment of cyclin expression may, therefore, refine current prognostic models if considered in relation to menopausal status. The prognostic relevance of cyclins is likely attributable to an influence on proliferation, cell survival and genetic instability. Awareness of the molecular mechanisms leading to deregulated cyclin expression may guide decisions for risk-adapted therapy regimens.
|
|
787. |
- Rutqvist, L E, et al.
(författare)
-
A systematic overview of radiation therapy effects in breast cancer
- 2003
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 532-545
-
Tidskriftsartikel (refereegranskat)abstract
- A systematic review of radiation therapy trials in several turnout types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41204 patients. The results were compared with those of a similar overview from 1996 including 285982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival. There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies. There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics. There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the turnout bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up. There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences. There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy. There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.
|
|
788. |
- Ruuth, Kristina, et al.
(författare)
-
Interferon-alpha promotes survival of human primary B-lymphocytes via phoshatidylinositol 3-kinase
- 2001
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Academic Press. - 0006-291X .- 1090-2104. ; 284:3, s. 583-586
-
Tidskriftsartikel (refereegranskat)abstract
- Signaling pathways for the antiviral and antiproliferative biological effects of type I interferons (IFN) are well established. In this report we demonstrate a novel signaling pathway for IFN-α, as it induced rapid phosphorylation of both PKB/Akt and its substrate forkhead. The PI3-kinase inhibitor LY294002 abolished these phosphorylations. PI3-kinase has been implicated in cell survival mediating its effect through the second messenger PIP3 and the subsequent activation of PKB/Akt. We could show that IFN-α inhibited spontaneous apoptosis of primary B-lymphocytes, in the absence of a mitogenic stimulus. This effect was inhibited by LY294002. Thus, our data suggests that IFN-α promotes survival of peripheral B-lymphocytes via the PI3-kinase-PKB/Akt pathway. In addition, IFN-α stimulation of anti-IgM activated cells resulted in downregulated expression of the cell cycle inhibitor p27/Kip1.
|
|
789. |
- Rydén, Lisa, et al.
(författare)
-
Assessment of microvessel density in core needle biopsy specimen in breast cancer
- 2004
-
Ingår i: Anticancer research. - 1791-7530. ; 24:1, s. 371-375
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: Estimation of microvessel density (MVD) in primary breast cancer in core needle biopsies (CNB) may predict response to systemic therapy. The aim of the present study was to explore the accuracy of assessment of MVD in CNB related to MVD in excised tumours. MATERIAL AND METHODS: MVD was estimated in core biopsies and subsequently excised tumours in 54 consecutive patients with breast cancer without pre-operative treatment. RESULTS: The correlation between MVD in CNB and excised tumours was non-significant. However, in tumours larger than 20 mm (r=0.56, p=0.005) and in lobular carcinomas (r=0.55, p=0.014) a significant correlation was observed. CONCLUSION: The overall accuracy between estimation of MVD on CNB and excised breast tumours was non-significant. The usefulness of MVD in CNB as a marker of response to systemic therapy should be further validated before it can be used in clinical practice.
|
|
790. |
- Rydén, Lisa, et al.
(författare)
-
Decreased angiogenic activity in breast cancer in ever-users of oral contraceptive therapy--preliminary report
- 2003
-
Ingår i: Anticancer research. - 1791-7530. ; 23:3C, s. 2875-2878
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiogenic activity defined by microvessel density or measurement of vascular endothelial growth factor is a key process under physiological and malignant conditions in steroid hormone responding organs. The aim of this study was to relate microvessel density (MVD) in primary breast cancer to reproductive data and use of exogenous hormones. MATERIAL AND METHODS: MVD was calculated retrospectively in forty-two consecutive tumours and related to clinical, histopathological and gynecological data. RESULTS: Tumours in ever-users of oral contraceptive therapy (OC) had lower MVD (p = 0.002), a finding not explained by smaller tumour size or lower histological grade. There was no influence on MVD by other reproductive data. CONCLUSION: These preliminary data on a supposed interaction between the use of OC and angiogenesis in breast cancer indicate that biological properties in breast tumours may be altered by ever-use of OC, but have to be further explored in an extended number of patients.
|
|