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Biomedical subjects

K W Andersen

Publications and source records attributed to K W Andersen.

At least 37 records · Page 2Linked to original sources
PubMed1991

[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↗
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↗
PubMed1989

Experience with 7,604 bone scintigraphies at time of operation for breast cancer 1977-1987.

From 1977 to 1987, 7,604 out of a total of 20,483 Danish breast cancer patients had a bone scintigraphy in order to exclude or localise osseous metastases. The scintigrams were performed and interpreted at 14 local hospitals. In 1979, standardised guidelines for interpretation were agreed upon. Until 1983, the scintigrams were described centrally, based on the local reports. From 1979, the frequency of positive bone scintigrams suggesting bone metastases stabilised at about 5% of the patients compared with 12 and 20% in 1977-78. The local take-over of description did not change the frequency. The frequency was also stable from 1979 when evaluated in age groups. With increasing age the frequency of positive scintigrams increased. The frequency of positive scintigrams was significantly lower in patients entering a protocol than in those not entering a protocol. The conclusion is that on a nation-wide basis it is possible to establish a stable, uniform interpretation of bone scintigrams after a two-year introduction period.

Adult↗
PubMed1988

Adjuvant systemic treatment and the pattern of recurrences in patients with breast cancer.

The aim was to analyze the impact of adjuvant systemic treatment (AST) on the anatomical distribution, the number, and the temporal relationship of the first metastases in 635 patients (pts) with breast cancer. These patients participated in the prospective studies of AST of the Danish Breast Cancer Cooperative Group (DBCG) 77-program. All patients had primary high-risk breast cancer (i.e. node positive or local invasion or tumor size greater than 5 cm). The initial treatment was mastectomy with axillary sampling, followed by postoperative radiotherapy. The types of AST and the number of patients with recurrence were: chemotherapy (CT), 134 pts; levamisole (LEV), 96 pts; tamoxifen (TAM), 154 pts. The pattern of recurrence in these patients was compared with the pattern of recurrence in 251 pts who did not receive AST (controls). Although CT reduced the total number of metastatic sites (P = 0.04), the incidence of liver metastases was increased compared to untreated controls (P = 0.02). The median number of metastatic sites was equal in TAM- and LEV-treated pts compared to controls. The incidence of lung metastases was increased in TAM-treated pts (P = 0.03), and LEV-treated pts had a decreased incidence of lymph node (P = 0.01) and pleural recurrences (P = 0.01) compared to controls. The results may suggest that mechanisms of clonal selection during the metastatic process involve differences in sensitivity to antineoplastic treatments of metastases at various anatomical locations.

Antineoplastic Agents↗
PubMed1988

Danish Breast Cancer Cooperative Group (DBCG). A description of the register of the nation-wide programme for primary breast cancer.

An account of the criteria for protocol allocation and of the various treatments in the DBCG programme is given together with some numerical representations. Furthermore the article explains how the DBCG programme has been run, including its randomization. Finally there is a description of the calculation of recurrence-free survival and survival. It is concluded that in the nation-wide programme there are only minor methodological errors, and that the conclusions based on the therapeutic outcome of the different therapies are reliable.

Breast Neoplasms↗
PubMed1988

A Danish randomized trial comparing breast-preserving therapy with mastectomy in mammary carcinoma. Preliminary results.

The present study comprises 847 women operated upon for invasive breast carcinoma at 19 surgical departments and enrolled in protocol DBCG-82TM from January 1983 to November 1987. Among them 662 (78%) were allocated for breast-preserving therapy or mastectomy by randomization, while 185 patients (22%) did not accept randomization. Within the randomized group 6% could not be entered into adjuvant protocols, i.e. subsequent programmes of postoperative therapy and follow-up. This left 619 evaluable patients. In the non-randomized series 26% did not fulfil the demands for entrance into the adjuvant protocols, leaving 136 evaluable patients, 60 of whom had chosen a breast-preserving operation and 76 mastectomy. In the randomized series the patients in the two treatment arms were comparable in age, menopausal status, site of tumour, pathoanatomical diameter of the tumour, number of removed axillary lymph nodes, number of metastatic axillary lymph nodes, and distribution on adjuvant regimens. Ninety per cent of the patients in the randomized group accepted the method offered, whereas 10% declined and wanted the alternate form of operation. The median follow-up period was approximately 1.75 years. The cumulative recurrence rate in the randomized group was 13% and in the non-randomized group 7%. These results are preliminary. Life-table analyses have not so far demonstrated differences in recurrence-free survival either in the randomized or the non-randomized series.

Adult↗
PubMed1988

Adjuvant therapy of premenopausal and menopausal high-risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group Trials 77-B and 82-B.

From September 1977 to November 1987 high-risk (i.e. with positive axillary lymph nodes, or tumor size greater than 5 cm or skin/facia invasion) premenopausal and menopausal breast cancer patients have been included in 2 randomized trials. In both trials the primary surgical treatment was total mastectomy with axillary sampling. In the first trial (DBCG 77-B) 1034 patients all received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment (0), 2) cyclophosphamide (C), or 3) cyclophosphamide + methotrexate + 5-fluorouracil (CMF). The chemotherapy was given for 1 year. With a median observation time of 7 years the actuarial survival after 9 years is 50, 60 and 65% respectively. Retrospectively, the survival benefit was observed to be most pronounced in patients with tumor size less than or equal to 5 cm and with less than or equal to 3 positive lymph nodes. In the subsequent study initiated in 1982 (82-B) all patients received CMF for 9 months. Furthermore they were randomized to 1) RT, 2) no further treatment, or 3) tamoxifen (TAM) for 1 year. As of November 1, 1987, 1308 patients have been included. At 4 years and with a median observation time of 2 years the survival is similar in the 3 groups. In conclusion, in high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT resulted in a 20-30% relative reduction in mortality at 9 years compared with RT alone. Preliminary analysis of adjuvant CMF + RT, compared with CMF alone or with CMF + TAM, shows after a median observation time of more than 2 years no significant survival differences.

Adult↗
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↗
PubMed1987

Stage and pattern of metastases in patients with breast cancer.

This study compares the pattern of metastases in 228 patients with initial stage I and 635 patients with initial stage II breast cancer. All these patients had recurrence within a median time of follow-up of 4.9 years (range 2.0-7.0 years). All patients were initially mastectomized, and staging was based on histopathological evaluation of mastectomy specimens. Patients with stage II disease received postoperative radiotherapy; 67% also received systemic adjuvant therapy. Locoregional recurrences were the most common sites of recurrence in stage I, whereas distant metastases occurred more often in stage II patients. Stage II patients had a significantly higher number of metastatic sites than stage I patients. Among patients with a single site of recurrence the frequency of local or regional recurrence was 62% in stage I patients compared to 16% in stage II patients. When correcting for this difference, which was ascribed to the effect of radiotherapy, the number and the distribution of metastatic sites were almost equal in stage I and II patients. The anatomical distribution of metastatic sites in different periods after mastectomy was almost the same in stage I and stage II patients; extraregional lymph node metastases, however, occurred earlier in stage II than in stage I patients. The recurrence-free interval, the survival after recurrence (SAR), and the overall survival were all significantly shorter for stage II than for stage I patients. The reduced SAR for patients with stage II disease hints that tumours of higher stages have a higher rate of progression. The progression time, however, was of the same duration in patients with initial stage I and II breast cancer. The prognostic significance of the classification of patients with breast cancer according to stage does not seem to discriminate tumours with different biological properties with regard to the rate as well as the pattern of dissemination. Postmastectomy follow-up of patients with stage I and II disease should therefore, follow the same guide-lines. Since the anatomical distribution of metastases was the same in different periods after mastectomy, the screening for recurrent disease should not be directed towards any specific sites in certain periods after initial diagnosis.

Adult↗
PubMed1987

Bone metastases in primary operable breast cancer. The role of a yearly scintigraphy.

In 231 patients with primary operable breast cancer bone scintigraphies were performed yearly from the second to the 6th year until recurrence irrespective of localization was diagnosed, another cancer was detected, or the patient refused further follow-up or died. During the observation period (from 2 up to 7 years after surgery) 13 patients (5.6%) had bone metastases verified by X-ray or histology within 12 months after the last bone scintigraphy. The scintigraphy was positive in only 7 of these patients. The yearly incidence of bone metastases varied between 0.6 and 2.6%. Due to this low incidence and a low cost/benefit, we conclude that a fixed schedule of repeated scintigraphies in primary operable breast cancer patients otherwise free of apparent disease is not justified.

Bone Neoplasms↗
PubMed1987

Evidence of a castration-mediated effect of adjuvant cytotoxic chemotherapy in premenopausal breast cancer.

This prospective randomized trial, conducted by the Danish Breast Cancer Cooperative Group, is the largest study, so far, of adjuvant chemotherapy in premenopausal breast cancer. The trial is unique in that it is nationwide and based on a nonselected population of patients, and is the only adjuvant trial studying the effect of cyclophosphamide monotherapy. After total mastectomy with axillary node sampling, followed by local radiotherapy, 1,032 pre- and perimenopausal women with operable breast cancer were randomized to observation alone, or to adjuvant chemotherapy for 1 year with either cyclophosphamide monotherapy or with a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). As of January 1987, median follow-up was 68 months. From early on both cyclophosphamide alone and CMF were found to improve recurrence-free survival (RFS) significantly and to a similar degree (P = .0001). However, an overall survival advantage did not become evident until 5 years after the start of treatment. So far, this advantage appears to be more pronounced in CMF (P = .0065) than in cyclophosphamide-only patients (P = .08). Thus, the study confirms the findings of the National Surgical Adjuvant Breast Project (NSABP) and Milan trials that adjuvant chemotherapy prolongs the survival of premenopausal women with early breast cancer. A retrospective analysis revealed that, in contrast with CMF, cyclophosphamide alone did not improve RFS significantly in subsets of patients without amenorrhea, with estrogen-receptor (ER) negative tumors, and with tumors of low histological differentiation. Assuming that cyclophosphamide alone is a less tumoricidal treatment than CMF, these findings suggest that the effect of adjuvant cytotoxic chemotherapy is mediated partly through chemical castration, and partly through a purely cytotoxic effect.

Adult↗
PubMed1986

Prognostic usefulness of estrogen receptor immunocytochemical assays for human breast cancer.

Breast cancers of postmenopausal patients at high risk for recurrence participating in an adjuvant therapy protocol were independently assayed for estrogen receptor by conventional dextran-coated charcoal steroid binding assays and by immunocytochemistry (ER-ICA) to compare the two assays and to assess the prognostic usefulness of ER-ICA. The ER-ICA was based on a monoclonal antibody to the estrogen receptor and was applied to lightly fixed, frozen sections of the cancers. Excellent agreement was found between the two estrogen receptor methods. It was found that a combination of the distribution of ER-ICA stained cells and the overall staining intensity gave a statistically significant correlation with the quantitative estrogen receptor dextran-coated charcoal steroid binding assay value. In addition, the overall appraisal of the lesion as ER-ICA positive or negative as well as the ER-ICA staining intensity and proportion of ER-ICA stained cancer cells related to patient disease-free interval and survival, independent of patient lymph node involvement. This relationship of ER-ICA status to prognosis appeared not to relate only to responses to adjuvant tamoxifen treatment since it also was observed with patients who did not receive the antiestrogen.

Breast Neoplasms↗
PubMed1986

Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone.

The therapeutic efficacy of combined endocrine therapy with tamoxifen, aminoglutethimide and hydrocortisone (T+AG+H) was evaluated against treatment with tamoxifen (T) alone in 210 patients above 65 years of age with metastatic breast cancer. The treatment results have been assessed for the 166 fully evaluable patients and were the following for the T and T+AG+H groups, respectively: PD: 31 and 35%; NC: 35 and 37%; PR: 13 and 16%; and CR: 21 and 12%. The overall treatment results are not statistically different (p = 0.35) and the 95% C.L. of the difference of the response rates are -8% to +20%. The median duration of remission was approximately 24 months in both treatment groups (p = 0.31). The time to treatment failure was comparable with median values of 10 and 8 months in the T and the T+AG+H groups respectively (p = 0.17). Toxicity was more frequent and severe in the combined treatment group and could in most instances be attributed to treatment with AG+H. In conclusion, the simultaneous use of T and AG and H does not seem to improve the therapeutic results in postmenopausal patients with advanced breast cancer.

Aged↗
PubMed1986

Steroid hormone receptors as prognostic indicators in primary breast cancer.

Recurrence-free survival (RFS) has been evaluated with regard to estrogen and progesterone receptor (ER and PgR) status for 145 postmenopausal women with primary breast cancer at high risk for recurrent disease. All patients received only local-regional therapy as an adjuvant therapy (DBCG protocol 77-c patients). ER+ patients had a significantly longer RFS than ER-patients. This difference was apparent using a cut-off level of 10 fmol/mg cytosol protein to distinguish between ER+ and ER-patients. There was no apparent difference in patients with high (greater than = 100 fmol/mg cytosol protein) ER levels vs. those with intermediate (10-99 fmol/mg cytosol protein) levels, indicating that the prognostic value of ER determinations in the natural course of the disease resides in a qualitative rather than a quantitative distinction among patients. No difference in RFS was found patients when patient were subdivided according to PgR status. The clinical applicability of the ER-ICA assay method for ER determinations is demonstrated in a subset of patients, some of whom received adjuvant endocrine therapy.

Actuarial Analysis↗
PubMed1986

Adjuvant tamoxifen in postmenopausal high-risk breast cancer patients: present status of Danish Breast Cancer Cooperative Group trials.

The aim of the present study was to analyze the efficacy of adjuvant tamoxifen (TAM) in postmenopausal patients with high-risk breast cancer. The primary surgical treatment was total mastectomy with axillary sampling. There were 1,650 eligible patients; 829 were randomized to receive postoperative radiotherapy (RT) and 821, to receive RT + TAM (10 mg three times daily for 1 yr). The 2 groups were identical with respect to age, tumor size, number of positive lymph nodes, degree of anaplasia, and estrogen and progesterone receptor content. Overall recurrence-free survival at 6 years was 39% in the RT group, compared to 48% in the RT + TAM group (P = 0.0008), but there was no significant difference in survival (P = 0.14). From retrospective analyses of recurrence-free survival according to prognostic variables, it appears that 4 subgroups of patients benefited from adjuvant TAM: those less than 69 years of age, those with 4 or more positive nodes, those with grade I-II tumors, and those with high estrogen receptor values (greater than 100 fmol/mg cytosol protein).

Aged↗