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M Blichert-Toft

Publications and source records attributed to M Blichert-Toft.

At least 73 records · Page 4Linked to original sources

High levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis.

The urokinase pathway of plasminogen activation is supposed to be involved in proteolytic degradation of the extracellular matrix during cancer invasion. The prognostic value of urokinase-type plasminogen activator (uPA) and type 1 plasminogen activator inhibitor (PAI-1) levels in cytosolic extracts of ductal breast carcinomas was studied, retrospectively, in 118 premenopausal and 72 postmenopausal high-risk patients entered into the protocol of Danish Breast Cancer Cooperative Group trials for adjuvant treatment of breast cancer. The median observation time was 8.5 years. uPA and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays. There is a strong correlation between these levels (P < 0.001; r = 0.57). Univariate analysis showed that a high uPA level is significantly associated with short overall survival in both premenopausal (P < 0.001) and postmenopausal (P = 0.03) patients, while a high PAI-1 content significantly predicts shorter overall survival in premenopausal (P = 0.005) and postmenopausal (P < 0.001) patients and shorter relapse-free survival in postmenopausal patients (P < 0.001). When the levels of uPA and PAI-1 are related to those of other prognostic parameters, both high uPA and high PAI-1 levels are associated with grade of anaplasia in premenopausal patients and with number of tumor-positive lymph nodes in postmenopausal patients. A high PAI-1 level is associated with low estrogen and progesterone receptor levels in both pre- and postmenopausal patients. The prognostic value of uPA and PAI-1 levels was compared with that of established prognostic parameters by multivariate analysis. In premenopausal patients, high uPA is an independent prognostic parameter for shorter overall survival, the relative risk being 2.0 (95% confidence interval, 1.1-3.7). In postmenopausal patients, a high PAI-1 level is a strong and independent factor in predicting shorter overall survival with a relative risk of 2.9 (95% confidence interval, 1.5-5.8). In this group of patients a high PAI-1 level is also an independent predictor of shorter relapse-free survival (relative risk, 2.1; 95% confidence interval, 1.1-3.9). These data together with previous reports indicate that uPA and PAI-1 are potentially important prognostic factors in breast cancer. This is in good agreement with the supposed function of uPA in cancer invasion. It is proposed that PAI-1 plays a role in protecting the tumor against degrading itself. Alternatively, the PAI-1 level may be a biochemical marker of tumor angiogenesis.

Adult↗

[The duct ectasia syndrome. A prospective clinical study of patients with breast diseases].

Mammary duct ectasia is a benign condition of the mammary gland histopathologically characterized by inflammatory changes in the collecting ducts. A prospective clinical and histopathological study was done of 316 consecutive patients with surgical mammary diseases. The syndrome of mammary duct ectasia (DES) was found in 42 patients (13%). The mean age was 44 years and 81% of the patients were pre- or menopausal. Forty-eight percent of the patients had a history of previous benign breast lesions and abnormality associated with lactation was also frequently represented in the history. Major symptoms were tumour formation, localised in the subareolar region in more than half of the cases, subareolar abscess and nipple discharge. Minor symptoms were mastalgia, mammary fistula, nipple retraction, general symptoms and enlarged axillary lymph nodes. Treatment for an abscess in DES seems to fail more often if only incision and drainage are performed. Excision of the entire focus and corresponding duct may prove to be better.

Adolescent↗

[The duct ectasia syndrome--an overlooked disease entity].

Mammary duct ectasia is a benign disease of the mammary gland, characterized by a frequently long history of tumour formation, nipple discharge, nipple retraction and mastalgia. Non-puerperal mammary abscess, which may be the presenting symptom, is also part of the syndrome. Diagnosis can often be made on the basis of the history and the clinical findings of nipple discharge, nipple retraction, tenderness on palpation, fistula formation and subareolar tumour/abscess formation. Mammography may guide diagnosis. Breast cancer is the most important differential diagnosis. If the clinical picture resembles cancer, it is necessary to perform diagnostic biopsy. Causal therapy of mammary duct ectasia is not available. Until now excision of the central mammary tissue and larger ducts has been used as treatment for the clinical manifestations of abscess, fistula and nipple discharge, apparently with good results.

Breast↗

[Primary hyperparathyroidism. An underdiagnosed disease in Denmark?].

Population-based investigations measuring serum calcium levels seem to indicate a prevalence of primary hyperparathyroidism (pHPT) of 0.4-1% in adults with a figure of about 3% in women over 60 years of age. Annual incidence rate varies and is found to be about 25-30 new cases per 100,000 adults with routine use of serum calcium measurements in diagnostic work-up. In women over 60 years of age the incidence approaches 200 instances per 100,000 individuals. Autopsy studies have demonstrated parathyroid disease in about 10%, one third as solitary adenomas and two thirds as hyperplasia. Annual incidence of surgical interventions, however, is currently found to be low with a frequency of about 2 instances per 100,000 inhabitants in Denmark, but with somewhat higher figures in Sweden and Finland. Recently, the preoperative diagnosis of pHPT has been considerably simplified and requires in most cases solely the demonstration of sustained raised serum calcium levels associated with elevated serum concentration of intact PTH. Investigations indicate that pHPT is underdiagnosed in Denmark, and indications for surgical treatment appear to be restrictive. Compared with Swedish operation series the weight of parathyroid adenomas in Danish series is found to be 3 times higher and the mass of hyperplasia 9 times higher consistent with significantly more elevated serum calcium concentrations. Arguments are presented in favour of an increased interest in diagnosing pHPT and a more liberal approach in the selection of patients for surgical treatment of mild or even asymptomatic disease. Routine measurement of serum calcium concentration in blood samples from patients might be considered in order to increase the incidence rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sarcomatoid tumours of the breast in Denmark from 1977 to 1987. A clinicopathological and immunohistochemical study of 100 cases.

One hundred sarcomatoid breast tumours, which had been diagnosed and registered in Denmark from January 1977 to January 1987, were subclassified using a combination of conventional morphological evaluation and immunohistochemistry, and the diagnosis was in each case related to clinical follow-up of 5-14 years or until death of the patient. Conventional histological examination resulted in 36 benign, 19 borderline and 18 malignant phyllodes tumours, 1 angiosarcoma and 26 non-specified sarcomatous tumours, 6 with small carcinoma-like foci. Immunohistochemical staining revealed that 23 of the non-phylloid sarcomatous tumours showed a tumour cell reaction for epithelial markers, predominantly cytokeratin and, therefore, the tumours were interpreted as metaplastic carcinomas. Clinical follow-up showed for phyllodes tumours and for the three cytokeratin-negative sarcomatous tumours local recurrence rates of 21 and 33%, respectively, whereas metastases only occurred from the angiosarcoma and from one borderline phyllodes tumour with five recurrences (5%). In contrast, metaplastic carcinomas gave rise to distant metastases in 50% of cases but no local recurrences. Axillary lymph nodes had been examined in 28 cases, 13 from metaplastic carcinomas. Only two of these showed metastatic spread, both with a pattern similar to the primary tumour. The differences in survival between patients with metaplastic carcinoma and patients with a borderline/malignant phyllodes tumour or a cytokeratin-negative sarcomatous tumour has in this study proven to be highly significant (P < 0.0001), and we find it of importance to use immunohistochemistry in the subclassification of sarcomatous breast tumours for appropriate surgery, reliable prognostic outlook and optimal postoperative therapy.

Actins↗

Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinomas and atypical lesions of the breast, 88 women, comprising 69 patients with lobular carcinoma in situ (LCIS) and 19 patients with combined lobular and ductal carcinoma in situ (LCIS + DCIS), were accrued from 1982 through 1987. All cases were treated with excision only. Within a median follow-up time of 61 months, a recurrence rate of 17% (15 cases) was found, excluding nine cases of refinding of LCIS. No contralateral recurrences occurred. The recurrences were in eight cases invasive carcinomas (IC), in six cases LCIS + DCIS, and in one case DCIS alone. The recurrence rates among cases of LCIS and of LCIS + DCIS were not significantly different. The histopathological review included an estimate of the number of lobules with LCIS and nuclear size, both of which were significantly related to recurrence. The risk of developing IC was calculated to be increased by a factor 11 as compared with the reference population.

Adult↗

[Axillary dissection in primary surgical treatment of breast cancer: risk of false-negative axillary status].

The present study evaluates the extent of axillary dissection as part of the primary surgical treatment of operable breast cancer. Data are from the period January 1979 to August 1990 and were collected prospectively as part of the Danish Breast Cancer Cooperative Group protocols for low-risk mammary carcinoma. The series consists of 6774 breast cancer patients aged 69 years or younger. The number of axillary lymph nodes removed was related to the frequency of ipsilateral axillary recurrence, recurrence-free survival, and overall survival after a median of five years follow-up, respectively. The recurrence-free survival and overall survival rate were directly related to the number of axillary lymph nodes removed. The difference in outcome is believed to be caused by false-negative classification of axillary-positive high-risk patients in groups of patients where only a few axillary lymph nodes were removed.

Adult↗

Ductal carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinoma of the breast, 112 women with ductal carcinoma in situ, treated with excision only, were registered from 1982 to 1987. Within a median follow-up of 53 months, a crude recurrence rate of 22% (25 cases) was found, of which five cases recurred as invasive carcinomas and 20 cases as in situ carcinomas. The histopathologic review included a single-parameter analysis of histological growth pattern, size of lesion, nuclear size, presence of comedonecrosis, and subhistologic type. A strong interrelationship was found for histological growth pattern, nuclear size, and comedonecrosis. These parameters were also significantly related to recurrence. Cases that had clinical symptoms had a high recurrence rate as compared with cases that were discovered by mammography only or incidentally.

Adult↗

Breast-conserving therapy for mammary carcinoma: psychosocial aspects, indications and limitations.

Breast-conserving therapy (BCT) for invasive cancer comprises complete tumour excision and axillary dissection, followed by irradiation. The object is to perform local treatment and determine the stage of disease on lines similar to those of mastectomy. In selected series of patients the efficacy of BCT has been equivalent to that of mastectomy with a view to distant relapse and survival. On the other hand, it has not been proved whether local relapse pattern is comparable to that of mastectomy, especially in high-risk patients. The advantage of BCT is of psychological nature, since preserving the configuration of the body maintains the sensation of female identity and body image to a better extent than that seen after mastectomy. BCT does not, however, reduce the high frequency of anxiety phenomena, mental instability, and depression. The selection of patients for BCT is based primarily upon a clinical-technical assessment, patient's preference and surgeon's preference, rather than eligibility based on biological risk factors. Demands on surgical technique, radicality of operation, and irradiation are important issues regarding local control. The relation between local recurrence rate and distant relapse will be discussed. The conclusion is that BCT is a method eligible for selected patients and that the increased used of mammography is going to extend the intake of patients for the method. However, it must be an obligation to keep following up the therapeutic results, in order not to lose the advantage of an early diagnosis by altered treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Classical prognostic factors in node-negative breast cancer: the DBCG experience.

Classical prognostic factors were analyzed in patients with low-risk primary breast cancer, defined as absence of tumor-positive axillary lymph nodes, tumor size less than or equal to 5 cm in diameter, and no invasion into skin or deep fascia. The primary surgical treatment was total mastectomy and lower axillary dissection. None of the patients received adjuvant therapy. Between 1977 and 1990, 7315 patients entered the study, and at the time of this analysis (January 1, 1990), the median follow-up time is 5 years. In univariate analyses, the following variables were significantly related to recurrence-free survival: age in premenopausal patients; tumor size; number of negative nodes removed; histological grade; and in premenopausal patients, estrogen receptor and progesterone (PgR) status. In multivariate analyses, age in premenopausal patients was the most important factor, followed by tumor size and histological grade, whereas PgR status in premenopausal patients was just of borderline significance. These variables should be included in multivariate analyses testing the value of more recently introduced prognostic factors.

Breast Neoplasms↗

Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group.

The Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma. From January 1983 to March 1989, the trial accrued a total of 1153 women. Of this number, 905 patients (79%) were randomly assigned to one of the two treatment options, whereas 248 patients (21%) did not accept randomization. Of the randomly assigned patients, 90% received the surgical option to which they had been originally assigned. In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination, and radiotherapy was subsequently administered to residual breast tissue. The axilla was dissected in all instances. Patient and tumor characteristics were similar in the two randomization arms. The median follow-up time was 40 months. At 6 years of life-table analysis the probability of recurrence-free survival was 70% in the breast conservation arm against 66% in the mastectomy arm. Survival figures were 79% against 82%, respectively.

Breast Neoplasms↗

[Rationalization profits of radiographic diagnosis with systematic follow-up DBCG (Danish Breast Cancer Cooperative Group) programs. 1].

In the follow-up programme of the DBCG-77 control and treatment protocols for primary operable breast cancer, bone scintigraphy and chest X-ray were performed 6 months after surgery and thereafter yearly until the diagnosis of any recurrence or another cancer. In the present study, the value of the two examinations was examined to the 6th year control. As a result of a low incidence of primary recurrence to the bone (0.6-3.9%) and to the chest (0.0-3.0%) the value was found to be low. About two thirds of the patients with primary chest recurrence addressed themselves with or had at the time of control pulmonary symptoms. About one half of those patients, in whom (during a 12-month period after the scheduled bone scintigraphy) bone metastases were diagnosed by another method, had a normal scheduled bone scintigraphy. False positive changes were not infrequent, especially at the bone scintigraphies. The diagnosis of asymptomatic chest recurrence did not reduce the mortality among stage II patients, among whom the greatest value of the control examination was found. It is concluded, that systematic use of bone scintigraphy and chest X-ray is not justified in a follow-up programme for stage I and II breast cancer patients.

Bone and Bones↗

[Prognosis after surgical treatment of breast cancer. 3. The low-risk group of the DBCG (Danish Breast Cancer Cooperative Group)].

The two therapeutic protocols of The Danish Breast Cancer Cooperative Group (DBCG) DBCG 77a (1977-1982) and 82a (1982-1990) comprise patients who were classified as low risk patients after operation for cancer of the breast, a total of 7,315 women. Treatment consisted of mastectomy and dissection of the lower and middle axillary levels. The median period of observation for DBCG 77a was 9 1/2 years and for DBCG 82a 3 1/3 years. The curves for recurrence-free survival and survival were found to be congruent in the two protocols. The recurrence-free survival after five years was 70% and 55% after ten years. Survival was 87% after five years and 70% after ten years. Local recurrence developed in 12.7% and 1.1% had distant recurrences simultaneously. Local recurrence was distributed with 60% in the scar or thoracic wall, 33% in the axilla and 7% in the clavicular lymph nodes. Distant recurrence alone developed in 11.4%. The time curves for development of local or distant recurrences were practically congruent. Local recurrence developed in 3.8% of the patients per annum during the first four years and after that in 1.5% per annum. Distant recurrence was found in 3.5% per annum in the first four years and after that in 1.8% per annum. The survival was significantly different after local and distant recurrence. Patients with tumours of grade 1 anaplasia had better prognoses than patient with grade 2 og 3 tumours as regards recurrence-free survival and survival. Multivariate analysis revealed that age under 40 years and anaplasia grad were significant prognostic variables for the parameters: distant recurrence and local recurrence. In addition, the number of lymph nodes in the operation specimen was a prognostic variable for local recurrence.

Adult↗

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial].

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

Aged↗