Biomedical subjects

B B Rasmussen

Publications and source records attributed to B B Rasmussen.

At least 55 records · Page 3Linked to original sources

PubMed1993

Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer.

The ability of oestrogen and progesterone receptor (ER and PgR, respectively) status to discriminate recurrence-free survival (RFS) among a cohort of consecutively accrued 952 postmenopausal patients has been studied. None of the cohort members investigated were treated with adjuvant therapy. Using a graduated scale of receptor status [low, intermediate and high receptor levels (< 10 vs. 10-107 vs. > or = 108 fmol/mg cytosol protein, respectively)] instead of the more commonly used dichotomous subdivision (positive vs. negative), ER level significantly discriminated between groups of patients with long vs. short RFS. Contrary to our expectations, patients with highest ER levels have as poor a prognosis as ER-negative patients, while patients with intermediate ER levels have longest RFS. The group of patients with ER levels > or = 108 fmol/mg cytosol protein comprises 47% of the cohort. The independent significance of overexpression of ER as a prognostic factor among this patient group is demonstrated in multivariate analysis where ER level is more significant than either grade of anaplasia or tumour size. PgR status did not significantly predict RFS among these patients. While the highest ER levels predispose for poorer prognosis among postmenopausal patients, it is precisely this group that experiences greatest benefit from adjuvant treatment with tamoxifen. Thus, patients who might otherwise go untreated due to their node-negative status can be readily identified and offered adjuvant treatment.

Adult↗

PubMed1992

Metastasis from squamous carcinoma of the cervix stage 1B to a borderline cystadenoma of the ovary.

A case of metastasis from squamous carcinoma stage 1B of the cervix to a borderline cystadenoma of the ovary is described. In addition, the patient had atypical endometrial hyperplasia. The patient underwent a radical hysterectomy with no adjuvant postoperative treatment and has resumed work, with no sign of recurrence one year postoperatively. The aspects of the metastasis to the ovary, multiple tumors in the genital tract and tumor-to-tumor metastasis are discussed. Reports on ovarian metastasis in low-stage squamous carcinoma of the cervix are few and it still seems justified to spare the ovaries at surgery in the young patient.

Carcinoma, Squamous Cell↗

PubMed1992

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↗

PubMed1991

Prognostic indicators of metastatic bone disease in human breast cancer.

The time to detection of metastatic bone disease (MBD) by radiographic examination was studied in 221 patients with advanced breast cancer. None of the patients had bone metastases by radiography or bone marrow carcinosis, evaluated by bilateral iliac crest biopsy. The period of follow-up after first recurrence was 46 months. Fifty-five patients (25%) had MBD; 89 patients died without MBD. The cumulated rate of MBD was 14% and 27% after 1 and 2 years, respectively. The actuarial time to MBD was associated significantly with the presence of positive regional lymph nodes at primary diagnosis, the occurrence of metastases in the mediastinum, and the presence of visceral metastases. Moreover, a positive bone scintigraphic scan at the time of first recurrence and abnormal biochemical analyses from serum also were associated significantly with a shortened time to MBD. Micrometastases in the bone marrow, as detected by monoclonal antibodies against epithelial markers (epithelial membrane antigen and cytokeratin), were present in 18% of the patients. The presence of such tumor cells was not associated with development of radiologic MBD. Cox analyses revealed that the result of bone scintigraphic scanning and the presence of visceral metastases were the most important and independent predictors of the time of MBD. Four distinct prognostic groups were identified based on the status of these two variables. The recognition of these prognostic groups has several implications for clinical and therapeutic management of patients with recurrent breast cancer.

Aged↗

PubMed1991

[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↗

PubMed1991

[Adjuvant chemotherapy in premenopausal and menopausal high-risk patients with breast cancer. 4. Results of the DBCG (Danish Breast Cancer Cooperative Group) 77B study].

From October 1977 to November 1982 premenopausal and menopausal high-risk breast cancer patients were included in a randomized trial (DBCG 77B). The primary surgical treatment was total mastectomy with axillary dissection. In the trial, a total of 1,034 patients were enrolled and received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment, 2) cyclophosphamide, or 3) cyclophosphamide + methotrexate + 5-fluorouracil. The chemotherapy was given for one year. With a median observation time of ten years, the survival was 45, 60 and 62%, respectively. Retrospectively, the survival benefit was observed to be most pronounced in the age group less than 40 years, in patients with tumour size less than or equal to 5 cm or with less than or equal to 3 positive lymph nodes. In high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT thus resulted in a more than 25% relative reduction in mortality at ten years of observation compared with RT alone.

Adult↗

PubMed1991

Estrogen receptor in primary breast cancer estimated in paraffin-embedded tissue. A study of its usefulness compared to dextran-coated charcoal assay.

Estrogen receptor (ER) was estimated immunohistochemically in formalin-fixed and paraffin-embedded tissue from the primary breast cancer in 349 postmenopausal patients with a high risk of recurrence and compared with the results of dextran-coated charcoal assay. There was a highly significant correlation between the ER classification obtained by the two methods (p less than 10(-6)). Patients ER positive according to immunohistochemical estimate had a significantly longer disease-free survival (p less than 0.001) and survival (p less than 0.001) than ER negative patients. The DCC assay showed an advantage of ER positive patients of the same magnitude. The patients, who were followed for a median of 86 months, were a subset of 1,700 patients participating in the Danish Breast Cancer Cooperative Group's randomized trial of adjuvant tamoxifen (TAM) treatment. In the presently analyzed subset of patients there were no statistically significant difference in disease-free survival (p = 0.52) or survival (p = 0.54) between patients who received adjuvant TAM and the controls. The same was true for receptor-defined subgroups regardless if the ER receptor was estimated in paraffin-embedded tissue or by the dextran-coated charcoal method. The analyzed subset might have been too small for demonstrating a positive effect of adjuvant TAM treatment.

Breast Neoplasms↗

PubMed1990

Estrogen and progesterone receptors in acoustic neuromas.

Acoustic neuromas are more frequent, larger, and more vascular in women, and their growth rate increases during pregnancy. Estrogen receptors were claimed to be demonstrated in these neoplasms for the first time in 1981. Since then, numerous diverging studies, using various biochemical and histochemical methods, have been published on the contents of estrogen and progesterone receptors in acoustic neuromas. We determined the content of estrogen and progesterone receptors by means of an immunohistochemical method, using monoclonal antibodies, which has proved to be reliable, reasonably sensitive, and clinically relevant in other tissues, especially in breast carcinomas. No estrogen or progesterone receptors could be found in 18 consecutive acoustic neuromas from 7 men and 11 women, ranging in age from 26 to 73 years. The results do not support preoperative hormone treatment of acoustic neuromas.

Adult↗

PubMed1990

The prognostic value of immunohistochemical estrogen receptor analysis in paraffin-embedded and frozen sections versus that of steroid-binding assays.

Estrogen receptors (ER) were independently analyzed using dextran-coated charcoal assays (ER-DCC) and immunohistochemical assays in frozen (ER-ICA) and paraffin-embedded tissue (ER-PAR) from 130 human breast cancer specimens drawn from postmenopausal high-risk patients registered in the Danish Breast Cancer Cooperative Group. ER was best detected with the ER-DCC assay followed by the ER-ICA (relative sensitivity 87%) and the ER-PAR assays (relative sensitivity 71%). The semiquantified staining features of the immunohistochemical assays were statistically significantly correlated with each other and with ER-DCC. Analysis of disease-free interval (DFI) and overall survival (OS) showed that all assays allowed statistically significant discrimination between a high risk and a low risk group, although the sensitivity differences tended to be reflected as small differences in clinical discriminatory power. The patient groups were then stratified according to adjuvant treatment [radiotherapy (RT) versus radiotherapy and tamoxifen (RT + TAM)]. The survival advantage was tied primarily to the receptor status itself in the steroid-binding assays, but was linked to both the receptor status and the adjuvant treatment in the immunohistochemical assays. Thus, the relative risks in terms of DFI and OS were of the same relative magnitude in the RT and RT + TAM groups for ER-DCC assays using a cut-off level of 10 fmol/mg cytosol protein, while there were large differences in the relative risks between RT and RT + TAM groups for ER-ICA and ER-PAR assays. We conclude that an ER assay in fresh tissue should be given first priority, but if there is no fresh tissue, an ER assay in paraffin-embedded tissue offers a reasonably good alternative as a prognosticator and an equivalent alternative as a predictor of the response to endocrine treatment.

Breast Neoplasms↗

PubMed1989

Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary human breast cancer.

The Mr 52,000 cathepsin D is the precursor of a lysosomal protease secreted in excess by breast cancer cells. This protease can degrade extracellular matrices and proteoglycans and is induced by estrogens in estrogen receptor-positive breast cancer cell lines. In a 4- to 6-yr retrospective cohort study, the concentration of the total cathepsin D (precursor plus intermediate and mature chains) was assayed in cytosols of primary tumors from 242 pre/perimenopausal and 154 postmenopausal breast cancer patients in a solid-phase immunoassay using two specific monoclonal antibodies. Patients were initially divided into groups with low, intermediate, or high concentrations of cathepsin D corresponding to the quartiles of the overall distribution. Using these groupings, the level of Mr 52,000 cathepsin D was not significantly associated with the recognized prognostic factors of age, lymph node involvement, tumor size, and/or grade of anaplasia. A significant association was found between cathepsin D concentrations and estrogen receptor status only among pre/perimenopausal patients. Receptor-positive tumors (greater than or equal to 10 fmol of estrogen receptor/mg of cytosol protein) had a significantly greater proportion of patients with high Mr 52,000 cathepsin D concentrations. Patients with high Mr 52,000 cathepsin D concentrations (greater than 78 pmol/mg for pre/perimenopausal and greater than 24 for postmenopausal patients) have shorter recurrence-free survival (P = 0.06 for pre/peri- and P = 0.039 for postmenopausal patients) and have a trend toward shorter overall survival (P = 0.30 and P = 0.089 for pre/peri- and postmenopausal groups, respectively). In multivariate analysis, Mr 52,000 cathepsin D status was found to be an independent prognostic factor for recurrence-free survival of about the same import as lymph node status for both menopausal groups. This first retrospective study demonstrates that the level of Mr 52,000 cathepsin D in cytosol of primary breast cancer biopsies is an independent prognostic factor in predicting relapses in both pre/peri- and postmenopausal patients.

Adult↗

PubMed1989

Oestrogen receptor status of primary breast carcinomas and their metastases. Relation to pattern of spread and survival after recurrence.

Immunohistochemical antibody techniques for detection of oestrogen receptors (ER) were applied to formalin fixed, paraffin embedded sections from 62 primary breast cancers, the metastases of their original regional lymph nodes (29 cases), bone marrow carcinosis (43 cases) and liver metastases (20 cases). Forty per cent of the primary tumours and 31% of the regional lymph node metastases were ER positive; in contrast, less than 20% of liver and bone marrow metastases were ER positive. The ER status of regional lymph node metastases was concordant with that of the primary tumour in 90% of the cases. The concordance rate was 75% for liver metastases and 58% for bone metastases. Patients with ER positive primary tumours had recurrence significantly more often in bone; ER negative tumours recurred more often in the liver. The survival after recurrence (SAR) was significantly related to the ER status of the primary tumour and to that of the regional lymph node metastases. In contrast, the SAR was not associated with the ER status of bone marrow carcinosis or liver metastases. Cox analyses showed that age and ER status of the primary tumour were the most important independent prognostic factors compared to other clinical, therapeutic, pathoanatomical and biochemical features. The study supports the hypothesis that tumour cell clones with different ER content are selected and adapted to grow in various anatomical sites. Moreover, the ER status of the primary tumour seems to be more important for the prognosis than the ER status of bone and liver metastases.

Breast Neoplasms↗

PubMed1988

Immunocytochemical detection of progesterone receptor in breast cancer with monoclonal antibody. Relation to biochemical assay, disease-free survival, and clinical endocrine response.

A new immunocytochemical assay for progesterone receptor (PgR-ICA) employing the monoclonal antibody JZB 39 was used to study tumors from two series of patients with breast cancer. In Series 1 assay results were in agreement with those of biochemistry in 76% of 338 cases (P less than 0.001) and in 54% of 101 cases in Series 2 (P less than 0.001). Agreement was better in Series 1 because it included fresher, previously untouched specimens. There were 70 patients in Series 1 with known clinical endocrine response. A negative assay correlated with disease progression in 45 of 57 patients, significantly better than with biochemistry (P = 0.013). In comparing 39 women with rapid disease progression with 39 free of disease at 5.1 years, those with PgR-ICA-positive tumors were over four times more likely to remain disease-free than those with negative results (P = 0.007). Product moment life-table analysis of 79 patients from Series 2 showed a significantly better cumulative survival for those with PgR-ICA-positive tumors (P = 0.047). These findings indicate that PgR-ICA should be of value in planning therapy and predicting disease course in breast cancer patients.

Antibodies, Monoclonal↗

PubMed1988

Human-human hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocytes from breast cancer patients.

Lymphocytes from lymph nodes obtained from breast cancer patients undergoing mastectomy were fused with the 0467.3, UC729HF2, or KR-12 human cell lines, totaling 42 fusions with lymphocytes from 23 patients. A total of 1696 human-human hybridomas were generated, 675 (39.8%) of which produced human IgG and/or IgM. Seventy-three human hybridomas produced antibodies binding to autologous malignant breast tissue and/or MCF-7 cells, as assayed by immunohistology or by cell-binding enzyme-linked immunosorbent assay. Twelve of these hybridomas, all reacting with malignant breast tissue, were subcloned to stabilize the production of human immunoglobulin. The reaction patterns of these 12 human monoclonal antibodies were investigated further by immunohistology on formalin-fixed, paraffin-embedded tissues. The reaction patterns of the various antibodies showed substantial variation and the antibodies reacted with a varying frequency with antigens expressed by different malignant breast tumors. One of these antibodies, MAC 40/43 (IgM), reacted with malignant breast and colon carcinomas and other epithelial derived neoplasms but did not react with normal breast tissue or with other normal and malignant tissues tested, except for a weak reaction with certain normal epithelial tissues. The antigen defined by MAC 40/43 was identified as a Mr approximately equal to 47,000 glycoprotein.

Antibodies, Monoclonal↗

PubMed1988

Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C.

The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients (tumor greater than 5 cm, positive axillary nodes, or invasion to skin/fascia) were randomized after total mastectomy and axillary sampling to postoperative radiotherapy (control) or to radiotherapy plus treatment with tamoxifen (TAM), 30 mg daily for 1 year. A total of 1,716 patients entered the study. At 8 years of follow-up, (7 years median time of observation), we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality, which is significant for patients less than 70 years of age. Retrospectively, an increased recurrence-free survival in TAM treated patients was significant in the following subgroups: tumor less than 5 cm, positive lymph nodes, anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein. In the subsequent trial (DBCG 82 C), 1,347 postmenopausal patients less than 70 years were randomized to one of the following 3 regimens: radiotherapy + tamoxifen, 30 mg daily for 1 year (TAM), TAM alone, or TAM + CMF (CMF i.v. day 1 every 4 weeks x 9). The survival is similar in the 3 groups at 4 years (2 years median time of observation).

Aged↗

PubMed1988

DNA ploidy and S-phase fraction in primary breast carcinomas in relation to prognostic factors and survival for premenopausal patients at high risk for recurrent disease.

Fine needle aspiration on small tumour pieces from 153 premenopausal women with primary breast cancer at high risk for developing recurrent disease has been used for flow cytometric DNA analysis; 133 of the tumours had either one or more cell populations different from diploid or a single, diploid cell population with an aspiration cytology showing presence of typical tumour cells. The distribution of tumour cell populations in this material was rather unusual with a high number of tetraploid populations. There were significant differences between various DNA ploidy classes with respect to prognostic factors such as lymph node involvement and oestrogen and progesterone receptor status. The S-phase fraction was significantly lower for diploid tumour cell populations compared to aneuploid populations. Diploid tumours with high S-phase fraction were not correlated to prognostic factors usually indicating a poor prognosis. Patients with an aneuploid tumour cell population classified as medium aneuploid had a significantly shorter recurrence-free survival than the rest of the patients. No conclusion on the effect of adjuvant treatment for patients with different tumour cell populations can be made at present.

Breast Neoplasms↗

PubMed1988

Immunohistochemical steroid receptor detection in frozen breast cancer tissue. A multicenter investigation.

Now that monoclonal antibodies against the estrogen receptor (ER) have become available, it is possible to detect the presence of ER immunohistochemically. In order to evaluate the validity of the immunohistochemical (ERICA) method in a routine detection of ER, we have tested the method in a multicenter investigation. As reference is used a conventional biochemical assay, dextran-coated-charcoal assay (DCC). The investigation analyzes the validity of the ERICA-assay, including a semiquantitative estimation of the ER-content, when the method is used in several independent departments of pathology, and the interobserver variation of the analysis. The results show that the qualitative detection of ER, obtained by the ERICA-assay and the DCC-assay has a concordance of about 90% for all the participating departments. The concordance is around 60-70%, when a semiquantitative estimation of the ER-content is used. The interobserver variation is also very low, with full agreement in 58 of 59 cases. The ERICA-assay may, therefore, be a relevant alternative to the DCC-assay. However, its clinical importance still has to be fully elucidated.

Antibodies, Monoclonal↗

PubMed1987

Prognostic value of steroid hormone receptors: multivariate analysis of systemically untreated patients with node negative primary breast cancer.

The value of estrogen and progesterone receptor (ER and PgR, respectively) determinations in predicting the recurrence-free survival (RFS) has been evaluated in a group of 807 node negative breast cancer patients. All of these patients are enrolled in the Danish Breast Cancer Cooperative Group (DBCG) 77-1a and 82-a protocols for low risk patients, and none of them have received systemic adjuvant therapy. At a median observation time of 50 months and in an evaluation of the total patient population as an entity, ER+ patients had only a marginally significant (P = 0.07) longer RFS than ER- patients while PgR+ patients experienced a significant advantage (P = 0.02). Among patients subgrouped according to menopausal status, both ER and PgR statuses were found to be significant prognostic factors for predicting RFS in the premenopausal women (less than 50 years) but not in peri- or postmenopausal women. Using Cox's multivariate analysis, nuclear pleomorphy was found to be the only significant prognostic variable, while the value of PgR status as a prognostic factor approached significance (P = 0.065). Although knowledge of ER status did not significantly improve distinction between patients with good and poor prognoses in the relatively small subgroup of premenopausal patients (n = 120) when PgR status was known, ER+PgR- patients have a lower risk of recurrence or death than ER-PgR- patients. Using a log-likelihood model, significant and distinct cut-off limits for the definition of receptor positivity were found for premenopausal patients: these were 5 fmol/mg cytosol protein for ER and 10 fmol/mg cytosol protein for PgR. These cut-off levels may reflect the ability of the ligand binding assay method used to discriminate between tissues with and without receptor proteins. Qualitative assessment of receptor status was as valuable as quantitative expression of receptor concentrations in predicting the RFS of the natural course of the disease among node negative premenopausal patients.

Adult↗

PubMed1987

Prognostic factors in primary mucinous breast carcinoma.

Two hundred seven mucinous breast carcinomas were morphologically classified into two different groups: pure mucinous carcinomas consisting only of areas with small epithelial islands of solid tumor floating in abundant extracellular mucin, and mixed carcinomas where the tumor contains large areas of mucin, as well as areas with infiltrating carcinoma devoid of extracellular mucin. Of the 207 tumors, 95 were of the pure type and 112 of the mixed type. The pure and mixed carcinomas differed significantly with respect to a number of prognostic factors, the most important of which was lymph node status. Patients with pure mucinous carcinomas had significantly fewer lymph node metastases at the time of primary operation (P = 0.0001) and a significantly longer recurrence-free survival (P = 0.03) than patients with mixed carcinomas. Patients with mixed carcinomas closely resembled patients with infiltrating ductal carcinomas not otherwise specified (NOS) with respect to both lymph node status and recurrence-free survival. In multivariate analysis, the single most important factor for predicting recurrence-free survival among the 207 patients was lymph node status. However, of 94 pure carcinomas, only 6 had lymph node metastases at the time of mastectomy. A detailed morphologic analysis demonstrated that two of these six cases were incorrectly diagnosed as being pure mucinous carcinomas--they were actually of the mixed type. In another two of these cases, the metastases originated from a co-existent infiltrating ductal carcinoma. Thus, metastases to the regional lymph nodes were observed in only two cases of pure mucinous carcinomas. It is concluded that the biologic behavior of the pure mucinous carcinomas differs from that of both the mixed carcinomas and infiltrating ductal carcinomas NOS. Thus, a new definition is suggested, in which a mucinous carcinoma is classified as such only if it is a pure carcinoma, and mixed mucinous carcinomas are classified according to the component without extracellular mucin production.

Adenocarcinoma, Mucinous↗