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Biomedical subjects

H T Mouridsen

Publications and source records attributed to H T Mouridsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Impact of axillary dissection on staging and regional control in breast tumors < or = 10 mm--the DBCG experience. The Danish Breast Cancer Cooperative Group (DBCG), Rigshisoutalet, Copenhagen, Denmark.

Data from 4771 patients with tumor diameters < or = 10 mm were analyzed. Results of surgery and pathoanatomical examinations indicated that nodal status was related to diameter, but not to number of nodes removed. More axillary metastases were found in group T1b tumors than in T1a. In 8% of tumors, at least 4 positive nodes were identified. Mean number of positive nodes was related to number of nodes removed, and when 10 or more nodes were removed a significantly lower axillary recurrence rate and better recurrence-free survival were demonstrated, confirming that axillary surgery has two goals: staging and regional disease control. Age, receptor status, grade and histological type, but not tumor location, were related to prognosis. In accordance with the classical prognostic factors, it was not possible to define a patient group where axillary surgery was superfluous. We conclude that proper staging and regional control renders a full axillary level I-II dissection necessary.

Adult↗
PubMed2000

Rationale and use of epirubicin-based therapy in the adjuvant setting.

The taxanes paclitaxel and docetaxel have an important role in the treatment of breast cancer, and numerous randomized trials have evaluated their efficacy for this indication. A systematic, evidence-based review was performed, which included all randomized, controlled trials evaluating taxanes for the treatment of early- or advanced-stage breast cancer that were identified in CANCERLIT and MEDLINE searches. The primary objectives of this review were to determine the dose and schedule for each taxane that was associated with the most favorable therapeutic index, and to determine whether (and under what circumstances) the taxanes improved survival. The search revealed 18 randomized phase II (n=1) or phase III (n=17) trials. For metastatic breast cancer, the dose and schedule associated with the most favorable therapeutic index for paclitaxel was 175 mg/m2 given as a 3-hour infusion every 3 weeks, and docetaxel was 60-100 mg/m2 given as a 1-hour infusion every 3 weeks. Survival was improved under the following circumstances: (1) when 4 cycles of paclitaxel (175 mg/m2 every 3 weeks) was given following 4 cycles of conventional doxorubicin- cyclophosphamide for axillary node-positive operable breast cancer, (2) when trastuzumab was added to paclitaxel as first-line therapy for metastatic breast cancer that overexpressed HER2/neu, and (3) when docetaxel was given as second-line therapy for anthracycline-resistant disease. Although a survival benefit was found for taxanes as a component of first-line therapy in two of six trials, the interpretation of both positive trials was confounded by a lack of crossover to taxane therapy in those who were initially randomized to receive standard therapy. The taxanes improve survival in patients with early-stage breast cancer and selected patients with metastatic breast cancer. Further research is necessary in order to identify the efficacy of docetaxel relative to paclitaxel, the optimal dose of docetaxel, the role of weekly taxane therapy, the role of trastuzumab plus taxanes in early-stage disease, and whether taxanes are more effective when given concomitantly or sequentially in patients with early-stage disease

Antibiotics, Antineoplastic↗
PubMed1999

Reproductive history and stage of breast cancer.

A woman's reproductive history influences her risk of breast cancer. The authors hypothesized that reproductive history also influences stage of disease at the time of diagnosis. The authors analyzed a population-based cohort of 1.5 million Danish women born between 1935 and 1978 for whom individual information on births was available. Between 1978 and 1994, 10,790 incident cases of breast cancer in women under 60 years of age were identified. Nulliparous women compared with parous women and women with a late age at first birth compared with an early age were at significantly increased risk of being diagnosed with a large tumor and with cancer that had spread to regional lymph nodes. However, such an association was not seen for women diagnosed with a small tumor and women with cancer that had not spread to regional lymph nodes. Reproductive history did not appear to influence the time interval from first symptoms to first physician visit ("patient delay") or the time interval from first physician visit to surgery ("doctor delay"). The authors conclude that reproductive history is associated both with incidence of breast cancer and with stage of the disease at diagnosis, indicating possible influences on tumor progression and growth rate. Intensified awareness is warranted to achieve earlier diagnosis among nulliparous women and women with a late age at first childbirth, with the hope of improving their prognosis.

Adult↗
PubMed1999

Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial.

BACKGROUND: Postmastectomy radiotherapy is associated with a lower locoregional recurrence rate and improved disease-free and overall survival when combined with chemotherapy in premenopausal high-risk breast-cancer patients. However, whether the same benefits apply also in postmenopausal women treated with adjuvant tamoxifen for similar high-risk cancer is unclear. In a randomised trial among postmenopausal women who had undergone mastectomy, we compared adjuvant tamoxifen alone with tamoxifen plus postoperative radiotherapy. METHODS: Between 1982 and 1990, postmenopausal women with high-risk breast cancer (stage II or III) were randomly assigned adjuvant tamoxifen (30 mg daily for 1 year) alone (689) or with postoperative radiotherapy to the chest wall and regional lymph nodes (686). Median follow-up was 123 months. The endpoints were first site of recurrence (locoregional recurrence, distant metastases, or both), and disease-free and overall survival. FINDINGS: Locoregional recurrence occurred in 52 (8%) of the radiotherapy plus tamoxifen group and 242 (35%) of the tamoxifen only group (p<0.001). In total there were 321 (47%) and 411 (60%) recurrences, respectively. Disease-free survival was 36% in the radiotherapy plus tamoxifen group and 24% in the tamoxifen alone group (p<0.001). Overall survival was also higher in the radiotherapy group (385 vs 434 deaths; survival 45 vs 36% at 10 years, p=0.03). INTERPRETATION: Postoperative radiotherapy decreased the risk of locoregional recurrence and was associated with improved survival in high-risk postmenopausal breast-cancer patients after mastectomy and limited axillary dissection, with 1 year of adjuvant tamoxifen treatment. Improved survival in high-risk breast cancer can best be achieved by a strategy of both locoregional and systemic tumour control.

Antineoplastic Agents, Hormonal↗
PubMed1999

Anxiety and depression in breast cancer patients at low risk of recurrence compared with the general population: a valid comparison?

Breast cancer and its treatment have been associated with psychological morbidity. In this study our aim was to quantify the excess anxiety and depression resulting from breast cancer. We compared 538 newly diagnosed breast cancer patients at low risk of recurrence (87.0% responded) to 872 women randomly selected from the Danish general population (69.7% responded) using the Hospital Anxiety and Depression Scale (HADS). Contrary to expectations, the proportions classified as "cases" of anxiety and depression were not significantly different in the two groups. The breast cancer patients' mean HADS scores were significantly lower than those in the general population sample (anxiety, P = 0.021; depression, P < 0.001), indicating less anxiety and depression. However, we question the validity of this comparison. The HADS may not be suitable for use in the general population and there may be methodological problems in comparisons of groups whose life situations are very different.

Adult↗
PubMed1999

Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer--a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group. Danish Breast Cancer Cooperative Group (DBCG).

To evaluate the substitution of methotrexate with doxorubicin (Dox) in CMF-(cyclophosphamide, methotrexate, 5-fluorouracil) containing regimen for advanced breast cancer, 415 postmenopausal patients below the age of 66 years, naïve to chemotherapy, were accrued from 1980 to 1984 and followed-up until 1995. They received tamoxifen 30 mg daily orally and by randomisation either 400 mg/m2, cyclophosphamide, 25 mg/m2 doxorubicin and 500 mg/m2 5-fluorouracil (CAF) or 40 mg/m2 methotrexate instead of Dox (CMF) intravenously (i.v.) days 1 + 8 repeated every 4 weeks. Dox was substituted by methotrexate at a cumulative dose of 550 mg/m2. Among 341 eligible patients the response rate and median time to progression was significantly in favour of CAF: 53% CAF versus 36% CMF (P = 0.002) and 11.8 months CAF versus 6.5 months CMF (P = 0.001). Median duration of response was 19.5 CAF versus 18.0 CMF months, and survival 20.8 CAF versus 17.4 CMF months (non-significant). The two regimens were equimyelotoxic. There were no treatment-related fatalities but 1 patient with congestive heart failure on CAF was reported. Nausea/vomiting, stomatitis and infections were modest in both groups, whilst alopecia was more common with CAF. Regression analysis showed that long recurrence free interval, good performance status, and no visceral involvement was significantly related to long-term survival, whilst the treatment regimen was not. It is concluded that in chemotherapy-naïve patients with advanced breast cancer Dox-containing regimens are superior and remain the first choice of chemotherapy, especially in patients with visceral metastases, until newer drugs and combinations have been proven to be superior.

Adult↗
PubMed1999

Oral clodronate in breast cancer patients with bone metastases: a randomized study.

OBJECTIVES: To investigate the effect of the bisphosphonate clodronate on the occurrence of skeletal events (hypercalcaemia, fractures and radiotherapy) in breast cancer patients with bone metastases. DESIGN: Prospective, randomized, controlled, clinical trial. SETTING: A department of oncology in a university hospital. SUBJECTS: One hundred patients who received firstline systemic antineoplastic treatment for metastatic breast cancer with bone involvement were randomized to receive clodronate as two 400 mg capsules twice a day for 2 years or no additional therapy. RESULTS: In the clodronate group the number of skeletal events was reduced to 14 events in 48 evaluable patients as compared with 21 events in 51 evaluable control patients. The time to the first skeletal event was significantly longer in the clodronate group than in the control group (P = 0.015) and the most distinct difference was a lower occurrence of fractures in the clodronate group (P = 0.023). After 15 months the effect of clodronate tended to decline as the need for radiotherapy increased in the clodronate group compared with the control group (P = 0.069). Significant improvements in several quality-of-life aspects were seen in both groups during the first 6 months, but there was no significant difference between the groups. No effect was observed on time to radiologically evaluated disease progression in bone or on survival. The most frequent side-effects resulting in discontinuation of clodronate were nausea and diarrhoea. CONCLUSION: Oral clodronate is associated with a temporary reduction of morbidity related to bone metastases in breast cancer patients.

Adult↗
PubMed1998

Nordic trials of adjuvant therapy in primary breast cancer.

The Scandinavian Breast Group (SBG), established in 1989, has members representing research, diagnosis, and treatment of breast cancer. In 1992 the SBG analyzed ongoing adjuvant trials in the Scandinavian countries. Many trials were analyzing similar questions, but a substantial proportion recruited an insufficient number of patients to enable valid conclusions within a reasonable time. As a result the SBG Clinical Trials Group was established to coordinate and organize trials in primary and advanced disease. Present activities include a study in premenopausal patients with node-positive, receptor-positive disease (CMF vs castration), a study in pre- and postmenopausal patients with node-positive, receptor-negative disease (CMF vs CEF), and a study in high-risk patients aged < 60 years (dose-escalating CEF vs three cycles of CEF followed by high-dose chemotherapy and autologous stem cell support). All these studies are planned to close during 1998. Another study has recently been activated. This enrolls patients with climacteric symptoms given previous treatment for in situ or invasive breast cancer, who are randomized to observation vs hormone replacement therapy for 2 years. Other groups are strongly encouraged to participate. Potential future activities are briefly described. Some of these will be undertaken in international collaboration.

Antineoplastic Agents, Hormonal↗
PubMed1998

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. EORTC Breast Cancer Cooperative Group.

The EORTC Breast Cancer Cooperative Group carried out a randomized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer. Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial, of whom 232 patients were eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(-2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin were 36% and 28% respectively (P = 0.173). The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P = 0.048) were significantly worse in the doxorubicin arm. Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure (CHF). At the dose levels used in this study, no statistical differences in response rate and survival were found between the two treatment arms. Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin.

Adult↗
PubMed1998

Parity, age at first childbirth and the prognosis of primary breast cancer.

Reproductive factors are known to be aetiologically important in breast cancer, but less is known regarding their effect on breast cancer prognosis. We have investigated the prognostic effect of age at first birth and total parity using data from the Danish Breast Cancer Cooperative Group that, since 1977, has collected population-based information on tumour characteristics, treatment regimes and follow-up status on Danish women with breast cancer. Details of pregnancy history were added from the Danish Civil Registration System and the National Birth Registry. Included in the study were 10,703 women with primary breast cancer. After adjusting for age and stage of disease (tumour size, axillary nodal status and histological grading), the number of full-term pregnancies was found without prognostic value. However, women with primary childbirth between 20 and 29 years experienced a significantly reduced risk of death compared with women with primary childbirth below the age of 20 years [20-24 years: relative risk (RR) = 0.88, 95% confidence interval (CI) 0.78-0.99; 25-29 years: RR = 0.80, 95% CI 0.70-0.91]. Further adjustment for oestrogen receptor status did not influence these results. The effect was not modified by age at diagnosis, tumour size or nodal status. In conclusion, low age at first childbirth, but not parity, was associated with a poor prognosis of breast cancer. We speculate whether women who develop breast cancer despite an early first full-term pregnancy might represent a selected group with a more malignant disease.

Adult↗
PubMed1998

Survival in breast cancer patients after the first episode of hypercalcaemia.

OBJECTIVES: To investigate hypercalcaemia (serum ionized calcium (S-Ca2+) > 1.35 mmol L(-1)) in breast cancer patients before and after the introduction of bisphosphonates and the effect of disease- and treatment-related factors on survival. DESIGN: Prospective and retrospective registration of covariates. SETTING: A department of oncology in a university hospital. SUBJECTS: A consecutive cohort of 212 hypercalcaemic patients never treated with bisphosphonate was identified prospectively (period 1) and 193 patients with metastases were classified into three groups: mild (S-Ca2+ < 1.48: n=102). moderate (1.48 < or = S-Ca2+ < or = 1.60; n=41). and severe hypercalcaemia (S-Ca2+ > 1.60 mmol L(-1); n=50). Fifty-one patients with severe hypercalcaemia all treated with bisphosphonate except one were identified retrospectively (period 2). RESULTS: For period 1 median survival was 6.7 months. Survival was significantly decreased in the two groups with the highest initial S-Ca2+ (P < 0.0001). Median survival times in severely hypercalcaemic patients from periods 1 and 2 were 1.4 (9 5(% confidence interval 0.8-2.1) and 2.2 (95% confidence interval 1.3-3.1) months, respectively. In a Cox model for period 1 significant covariates were: WHO performance, extent of metastases, whether systemic anticancer treatment could be given, and haemoglobin, but not S-Ca2+. CONCLUSION: Prognosis is poor in hypercalcaemic breast cancer patients with WHO performance 3-4 and advanced metastatic disease when effective systemic treatment can no longer be offered. Bisphosphonate treatment does not seem to improve survival in severe hypercalcaemia. Antihypercalcaemic treatment of mild malignancy-associated hypercalcaemia appears not to be vital. Therapeutic efforts should be aiming at patients with moderate hypercalcaemia.

Breast Neoplasms↗
PubMed1997

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.

Adult↗
PubMed1997

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

BACKGROUND: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). METHODS: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. RESULTS: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. CONCLUSIONS: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

Adult↗
PubMed1997

Should women be advised against pregnancy after breast-cancer treatment?

BACKGROUND: Oestrogen is an established growth factor in breast cancer. There has, therefore, been much discussion about whether women should be advised against becoming pregnant after breast-cancer treatment because of a possible negative prognostic effect from the high oestrogen concentrations associated with pregnancy. METHODS: We studied 5725 women with primary breast cancer. Information on these women was obtained from the Danish Breast Cancer Cooperative Group. Since 1977 this group has collected population-based data on tumour characteristics, treatment regimens, and follow-up status of Danish women with breast cancer. Details of reproductive history were obtained from The Danish Civil Registration System, the National Birth Registry, and the National induced Abortion registry. We estimated the relative risk of death among women who became pregnant after breast-cancer treatment compared with women who had not become pregnant. FINDINGS: 5725 women with primary breast cancer aged 45 years of younger at the time of diagnosis were followed up for 35,067 patient-years. Among these, 173 women became pregnant after treatment of breast cancer. Women who had a full-term pregnancy after breast-cancer treatment had a non-significantly reduced risk of death (relative risk 0.55 [95% CI 0.28-1.06]) compared with women who had had no full-term pregnancy after adjustment for age at diagnosis, stage of disease (tumour size, axillary nodal status, and histological grading), and reproductive history before diagnosis. The effect was also not significantly modified by age at diagnosis, tumour size, nodal status, or reproductive history before diagnosis of breast cancer. Neither miscarriages nor induced abortions after breast-cancer treatment influenced the prognosis. INTERPRETATION: We found no evidence that a pregnancy after breast-cancer treatment increased the risk of a poor outcome.

Abortion, Induced↗
PubMed1997

Quality control of end results in a Danish adjuvant breast cancer multi-center study.

In a Danish multi-center study, quality control was performed on off-study data for high-risk breast cancer patients included in protocols of adjuvant therapy. In the two protocols 4455 patients were randomized and 2477 were registered off-study. Data from these patients were validated by reviewing the patients' records. Incorrect data were observed in 16.2% of the cases who went off-study due to recurrence, other malignant disease or death. In 258 of 2133 patients unidentical locations were demonstrated. Of these, 104 showed a time difference also. A major difference in site of recurrence was found in 107 patients (5.0%), 43 of whom were upstaged from local to a distant recurrence and 64 were downstaged. A time difference of more than 30 days was found in 192 patients (9.0%) and in 17 the difference exceeded 366 days. A time difference only was found in 88 patients (4%). The major parameter in the statistical analysis of the two protocols, i.e. recurrence-free survival, was not significantly influenced by the validation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Molecular cytogenetic analysis of a nontumorigenic human breast epithelial cell line that eventually turns tumorigenic: validation of an analytical approach combining karyotyping, comparative genomic hybridization, chromosome painting, and single-locus fluorescence in situ hybridization.

The immortalized, nontumorigenic human breast epithelial cell line HMT-3522 has been used as a model for premalignant and, eventually, malignant development. During cultivation, the karyotype evolution was followed. At an early stage, a very long constant phase showed a near-diploid karyotype, with only five marker chromosomes. DNA from this phase was used for comparative genomic hybridization (CGH) analysis, confirming a previously known MYC amplification, and the integration sites were subsequently determined by single-locus fluorescence in situ hybridization (FISH). Furthermore, gains of 5q22-qter and 20q11-qter and deletion of most of chromosome 6 (6p23-qter) were detected by CGH. Because of uncertainty about some of the indicated changes, including a deletion of Ip35-pter, the CGH findings were investigated more closely by chromosome painting, leading to a revision of the karyotype: 45,XX,del(I)(p35),-6,dup(8)(pter-->qter::qter-->q24),der(12) t(6;12)(p23; p13),der(14)t(5;14)(q22;q32.3),der(17)t(8;17;20)(17pter-->17q25 ::8qter--> 8q23::8q24-->8qter::8q24-->8qter:: 8q23-->8q24.1::20q11-->20qter). Some karyotypic changes were confirmed by CGH; others had to be revised; and, in the Ip35 region, classical cytogenetics seems superior to CGH. However, CGH revealed a karyotypically unsuspected dup(20q) that might be of special relevance to breast tumor initiation or progression. Our study confirms that CGH is supplementary to current technologies, e.g., karyotyping and Southern analysis, but cannot replace them. In addition, our cell line turned out to be an excellent model for comparison among the different methods. The results imply that future cytogenetic analyses of complex karyotypes should be based on a combination of karyotyping, CGH, and FISH.

Breast↗
PubMed1997

Plasminogen activator inhibitor type 1 in cytosolic tumor extracts predicts prognosis in low-risk breast cancer patients.

We have reported previously that both urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) are statistically significant prognostic variables in patients with high-risk breast cancer (Grondahl-Hansen et al., Cancer Res., 53:2513-2521, 1993), and we recently described that the uPA receptor (uPAR) is a prognostic marker in postmenopausal, node-positive breast cancer patients (Grondahl-Hansen et al., Clin. Cancer Res., 1:1079-1087, 1995). The present retrospective study describes the prognostic impact of uPA, its receptor uPAR, and PAI-1 in breast cancer cytosol from 111 low-risk premenopausal patients and 184 low-risk postmenopausal patients with a median follow-up of 6.0 years (range, 3.8-14.9) and 7.4 (range, 3.7-14.0) years, respectively. uPA, uPAR, and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays, and data were dichotomized using the median value as the cutoff for calculation of recurrence-free survival and overall survival. A correlation was found between the levels of each of the three molecules. In univariate analysis, high PAI-1 was significantly associated with short overall survival in postmenopausal patients [relative risk (RR), 2.3; 95% confidence interval (CI), 1.3-4.3; P = 0.005] and shorter recurrence-free survival in both premenopausal (RR, 2.5; 95% CI, 1.3-4.7; P = 0.004) and postmenopausal (RR, 1.8; 95% CI, 1.1-2.9; P = 0.02) patients. Neither uPA nor uPAR reached statistical significance in the univariate analyses. The prognostic value of uPA, uPAR, and PAI-1 was then compared with that of other established prognostic variables by multivariate analysis. PAI-1 was an independent prognostic variable for recurrence-free survival in premenopausal patients, with a RR of 2.6 (95% CI, 1.3-5.0). For recurrence-free survival (RR, 1.9; 95% CI, 1.1-3.5) and overall survival (RR, 2.6; 95% CI, 1.2-5.7) in postmenopausal patients, PAI-1 was the only independent variable left in this group of patients. Neither uPA nor uPAR reached significance in the multivariate analysis. These data, together with previously published data on the prognostic significance of components of the urokinase plasminogen activation system in breast cancer cytosols, strongly indicate that PAI-1 is a statistically significant and independent prognostic marker in both low- and high-risk breast cancer patients.

Adult↗