Showing papers by "Henning T. Mouridsen published in 2006"
TL;DR: This study shows that semi-quantitative scoring of 2 mm cores on TMA is feasible for several potential markers for endocrine therapy, and has great potential in both retrospective and prospective studies aiming at improving the prediction of response to endocrine treatment.
Abstract: Aim: To assess whether immunohistochemically stained tissue microarrays (TMA) of 2 mm cores from paraffin embedded tumour tissue may replace whole sections in semi-quantitative evaluation of selected potential markers for endocrine treatment. Methods: Whole sections and 2 mm cores on TMA were used for immunohistochemical staining of potential markers for endocrine treatment. The Allred scoring system was used for the markers with nuclear localisation: the oestrogen receptor, the progesterone receptor, p27 and the oestrogen receptor co-regulator amplified in breast cancer 1 (AIB1). The Allred scoring system was also used for the non-nuclear markers Bcl-2, pS2 and cyclooxygenase 2 (COX-2); the membrane receptors HER-2, insulin-like growth factor I receptor (IGF-IR) and epidermal growth factor receptor were quantified according to the guidelines for the Herceptest. Results: The data and statistical analyses showed that the semi-quantitative evaluation of oestrogen receptor, progesterone receptor, AIB1, COX-2, HER-2 and IGF-IR on TMA blocks was comparable with analysis on whole sections. Conclusions: This study shows that semi-quantitative scoring of 2 mm cores on TMA is feasible for several potential markers for endocrine therapy. Considering the small size of many breast tumours, the speed and cost-effectiveness of immunohistochemistry on TMA compared with whole sections, and the importance of the expression level of the proteins, semi-quantitative scoring on TMA has great potential in both retrospective and prospective studies aiming at improving the prediction of response to endocrine treatment.
97 citations
TL;DR: Elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to chemotherapy, and this study identified a group of patients with metastatic breast cancer, which hardly respond to the most frequently used chemotherapy regimes.
Abstract: Purpose: Only about 50% of metastatic breast cancer patients benefit from cytotoxic chemotherapy. Today, no validated markers exist for prediction of chemotherapy sensitivity/resistance in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis, and the purpose of the present study was to test the hypothesis that tumors expressing high levels of TIMP-1 are protected against apoptosis-inducing agents and thus less sensitive to apoptosis-inducing chemotherapeutic drugs. Experimental Design: We investigated the association between primary tumor expression levels of TIMP-1 protein and objective response to first-line chemotherapy in 173 patients with metastatic breast cancer. Results: When analyzed as a continuous log-transformed variable, increasing TIMP-1 levels were significantly associated with lack of response to cyclophosphamide/methotrexate/5-fluorouracil and anthracycline-based chemotherapy ( P = 0.01; odds ratio, 2.0; 95% confidence interval, 1.1-3.3). In a multivariate model, including lymph node status, steroid hormone receptor status, menopausal status, dominant metastases site, type of chemotherapy, and disease-free interval, TIMP-1 was significantly associated with resistance to treatment ( P = 0.03; odds ratio, 1.7; 95% confidence interval, 1.1-3.3). Conclusions: In the present exploratory study, we showed that elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to chemotherapy. By using TIMP-1, we identified a group of patients with metastatic breast cancer, which hardly respond to the most frequently used chemotherapy regimes (i.e., cyclophosphamide/methotrexate/5-fluorouracil and anthracyclines).
78 citations
TL;DR: Blation of ovarian function in premenopausal women with hormone receptor-positive breast cancer had a similar effect to CMF on disease-free and OS, and no significant interactions were demonstrated between treatment modality and hormone receptors, age, or any of the well-known prognostic factors.
Abstract: Purpose To compare the efficacy of ovarian ablation versus chemotherapy in early breast cancer patients with hormone receptor–positive disease. Patients and Methods We conducted an open, randomized, multicenter trial including premenopausal breast cancer patients with hormone receptor–positive tumors and either axillary lymph node metastases or tumors with a size of 5 cm or more. Patients were randomly assigned to ovarian ablation by irradiation or to nine courses of chemotherapy with intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) administered every 3 weeks. Results Between 1990 and May 1998, 762 patients were randomly assigned, and the present analysis is based on 358 first events. After a median follow-up time of 8.5 years, the unadjusted hazard ratio for disease-free survival in the ovarian ablation group compared with the CMF group was 0.99 (95% CI, 0.81 to 1.22). After a median follow-up time of 10.5 years, overall survival (OS) was similar in the two groups, with a hazard ratio o...
50 citations
TL;DR: Chemotherapy had more negative impact on health-related quality of life but preserved ovarian function in some younger patients, and CMF chemotherapy and ovarian ablation have similar impact on recurrence and survival.
Abstract: Background
Ovarian ablation is an effective adjuvant therapy for primary breast cancer but little is known about its quality of life impact relative to the more widely used adjuvant chemotherapy. This randomized study compared quality of life outcomes of adjuvant ovarian ablation versus cyclophosphamide, methotrexate, fluoracil (CMF) chemotherapy.
21 citations
TL;DR: Changes in lymph node status distribution explained half of the improvement in 5-year relative survival, and seem to be the single most important cause behind the improved survival of breast cancer patients in Denmark.
Abstract: We studied the impact on survival of changes in breast cancer patients' distribution by lymph node status at the time of diagnosis. Our study included breast cancer patients diagnosed from 1978 to 1994 in Denmark, where the treatment schemes for breast cancer patients were fairly stable, and where mammography screening was limited. We measured lymph node status by the proportion of positive lymph nodes of all excised lymph nodes, as assessed by a pathologist. This measure was available for two-thirds of the breast cancer patients. The outcome was 5-year relative survival. Changes in lymph node status distribution explained half of the improvement in 5-year relative survival, and seem to be the single most important cause behind the improved survival of breast cancer patients in Denmark.
3 citations
TL;DR: Although further studies are required to determine the optimum treatment strategy and duration of AI therapy, the third-generation AIs are proving highly effective agents in the treatment of HR+ early breast cancer, and bring into question the validity of tamoxifen as the gold standard for adjuvant therapy.
Abstract: In early breast cancer, adjuvant therapy significantly reduces the risk of recurrence after complete surgical resection of the tumor mass For over a decade, 5 years of adjuvant endocrine therapy with the selective estrogen receptor modulator tamoxifen has been the gold standard in hormone-receptor-positive (HR+) disease Despite therapy with tamoxifen, relapses still occur, and the rate of relapse is particularly high in the first 2–3 years after surgery More effective therapies are urgently required to prevent these relapses, particularly in patients with higher-risk disease The third-generation aromatase inhibitors (AIs), letrozole, anastrozole and exemestane, have shown greater efficacy than tamoxifen, with comparable tolerability, in large, randomized, phase III trials in the early adjuvant setting On the basis of these findings, AIs are now displacing tamoxifen as the preferred adjuvant endocrine therapy for HR+ early breast cancer in postmenopausal women Two treatment strategies have been used to investigate AI efficacy in the early adjuvant setting, both with 5 years’ tamoxifen as the comparator: upfront AI for 5 years, or switching to an AI after completing between 2 and 3 years of tamoxifen When given upfront, anastrozole (ATAC trial) and letrozole (BIG 1-98 trial) have been shown to significantly improve disease-free survival compared with tamoxifen Letrozole also significantly reduced the risk of distant recurrence, a well-recognized predictor of breast cancer death Indirect comparisons suggest that these two AIs may not be clinically equivalent, but a direct comparison of letrozole and anastrozole in a prospective, randomized trial is required to prove whether these two AIs do differ clinically Switching to exemestane or anastrozole therapy after 2–3 years of tamoxifen has also been shown to significantly reduce the risk of relapse compared with 5 years of tamoxifen therapy However, in these trials, randomization and/or analyses were initiated at the time of switching therapy, including only patients who remained disease-free at this time, thus excluding patients with higher-risk disease who had experienced early relapse, and selecting a more favorable patient population Trials comparing upfront AIs with the sequential approaches are ongoing: BIG 1-98 and amended TEAM Of note BIG 1-98 is the only trial to include both switching strategies: tamoxifen followed by letrozole and letrozole followed by tamoxifen Trials in the early adjuvant setting have revealed that AIs are generally well tolerated: side effects are predictable and manageable Although further studies are required to determine the optimum treatment strategy and duration of AI therapy, the third-generation AIs are proving highly effective agents in the treatment of HR+ early breast cancer, and bring into question the validity of tamoxifen as the gold standard for adjuvant therapy Recently updated international guidelines now recommend that early adjuvant therapy should include an AI
1 citations