Mitoxantrone and prednimustine combination chemotherapy in breast cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
M Kaufmann
Publications and source records attributed to M Kaufmann.
Expression of HLA-A, -B, -C, -DR, -DP, -DQ, and of HLA-D-associated invariant chain (Ii) in non-neoplastic mammary epithelium, fibroadenoma, adenoma, and carcinoma of the breast.
Non-neoplastic mammary gland, 20 benign tumors and 206 carcinomas of the breast were immunohistochemically examined for expression of HLA-A, -B, -C, HLA-DR, -DP, and -DQ molecules and the HLA-D associated invariant chain (Ii). In contrast to cells from benign lesions, tumor cells of 51.2% of carcinomas had an abnormally low content of HLA-A, -B, and -C determinants ranging from reduction of antigenic density per cell (28.8%) over an incomplete (15.6%) to complete loss of antigens (6.8%). Associated with lymphohistiocytic stromal infiltrates, HLA-D/Ii determinants were found to be induced in benign duct and acinar epithelium after the order Ii greater than or equal to HLA-DR greater than or equal to HLA-DP greater than or equal to HLA-DQ. These antigens were also expressed, mostly noncoordinately, in 55.5% of carcinomas, and in 98 cases according to the above order. In 28.6%, Ii expression clearly exceeded HLA-D antigen expression; conversely, 6.2% contained HLA-DR+/Ii- tumor cell subsets. In breast carcinoma, the association of reduced HLA-A, -B, and -C expression and a noninduction of HLA-DR was highly significant (P less than 0.0009), suggesting an abnormal signal acting down-regulating on the expression of both classes of antigens. Because the modality of HLA-A, -B, and -C and HLA-D/Ii expression correlated with neither tumor type nor grade, it might be an independent parameter.
Adenofibroma↗
Correlation of DNA flow cytometric results and other prognostic factors in primary breast cancer.
The percentage of cells in S-phase and DNA-ploidy have been measured in 300 primary mammary carcinomas by means of DNA-flow cytometry (FCM). The data were compared with the age and menopausal status of the patients as well as with the size, regional lymph-node involvement, histologic type, grade and concentration of estrogen (ER) and progesterone (PR) receptors of the tumors. A DNA-diploid distribution of the G0/1-peak was found in 37.6% of the cases. The mean percentage of S-phase fractions was 4.83. DNA-aneuploid tumors had significantly higher amounts of S-phase fractions (6.12%) than DNA-diploid tumors (2.66%). There was also a significant correlation between the DNA measurement data (DNA-ploidy and S-phase fractions) and histologic grade, as well as the content of ER and PR, but not between DNA-ploidy, S-phase fractions, tumor size (T) and evidence of axillary lymph-node metastases. DNA-FCM gives a biological characterization of the tumor in addition to the histopathologic examination. The method can be used as a routine procedure because of the reliability and reproducibility of the results as well as the short time needed for the measurements.
Age Factors↗
Psychotherapy in support of patients undergoing antineoplastic chemotherapy.
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Antineoplastic Agents↗
Comparison of in vivo and in vitro activity of estrogen-linked nitrosoureas in methylnitrosourea-induced rat mammary carcinoma.
The anticancer activity of estradiol-linked 2-chloroethylnitrosoureas in methylnitrosourea-induced rat mammary carcinoma was investigated using the short-term assay and the bilayer soft agar system after in vitro exposure as well as the monolayer methylcellulose assay following in vivo treatment. The aim was to evaluate to what extent previous in vivo findings are paralleled by the results of two in vitro test systems and the monolayer culture technique ex vivo. From the test systems investigated and under the conditions used, the results of the short-term test and the monolayer methylcellulose assay did not show a correlation with previous in vivo findings. Only the results of the bilayer clonogenic assay paralleled therapeutic parameters in vivo, although the degree of activity obtained in vivo was not reflected in vitro.
Animals↗
The value of bone marrow examination for tumor staging in breast cancer.
The purpose of our study was to investigate the value of cytokeratin antibodies for identifying bone marrow involvement in breast cancer patients who showed no evidence of distant metastases using noninvasive tumor staging procedures. Bone marrow for histological (biopsy) and immunocytochemical (aspiration) evaluation was obtained from the anterior iliac crest from 50 unselected consecutive women during surgical treatment of the primary tumor. The histological examination was done on nondecalcified bone sections. The immunocytochemical studies were carried out on interface smears of the bone marrow aspirates. For staining, cytokeratin antibodies (PKK 1) and the immune alkaline phosphatase method was used. Cytokeratin-positive cells were found in 4 of the 50 cases (8%). Of those 4 patients, however, 2 also showed evidence of neoplastic bone marrow infiltration histologically. We thus were able to prove that immunocytochemistry on aspirates is superior to conventional histology in identifying tumor in bone marrow. Nonetheless, our results clearly fell below the rate found in previous studies where epithelial membrane antigen antibodies were used.
Bone Marrow↗
In vitro evaluation of an estradiol-linked nitrosourea in mammary carcinomas of mouse, rat and man.
In vitro activity of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-ala-17-E2) at three concentrations in transplanted MXT mammary carcinoma in B6D2F1 mice and autochthonous methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats, as well as in 30 human primary breast carcinomas using the bilayer soft agar assay is described. Eighty-five per cent of MXT tumors showed a more than 70% inhibition of colony formation following CNC-ala-17-E2. In the MNU-induced model this high degree of inhibition was not observed: only 5% of individual tumors showed an inhibition up to 70%, but a superiority of the hormone-linked agent over the unlinked single agents was nevertheless discernible. In contrast, in human breast carcinomas a response at this sensitivity level could not be assessed. Thus, in the MXT mammary carcinoma the in vitro results paralleled previous findings in vivo, whereas in the MNU-induced autochthonous tumor model this close in vivo-in vitro correlation was not observed. The discrepancy between in vivo and in vitro results found in the autochthonous rat model indicates that hormone-linked nitrosoureas should not necessarily be abandoned for the treatment of human breast carcinoma on the basis of negative in vitro results alone.
Adult↗
Differential diagnosis of benign epithelial proliferations and carcinomas of the breast using antibodies to cytokeratins.
The immunohistochemical reactivity on frozen sections of diverse benign and malignant epithelial proliferations of human breast tissue from 156 patients was examined using antibodies to different cytokeratins. Antibodies recognizing cytokeratins 18 and 19 reacted with luminal epithelial cells but not with myoepithelial cells of normal mammary gland, cystic disease, adenosis, papilloma, and fibroadenoma or with a subpopulation of proliferating cells in sclerosing adenosis and epitheliosis. These antibodies reacted with the tumor cells of all in situ and invasive carcinomas. KA1 antibody, which by one- and two-dimensional gel electrophoresis and immunoblotting was shown to bind preferentially to cytokeratin 14 in a complex with cytokeratin 5, reacted with the nonproliferating myoepithelium of normal gland, cystic disease, adenosis, papilloma, fibroadenoma, and in situ carcinoma; it also reacted with a subpopulation of proliferating cells in sclerosing adenosis and epitheliosis (papillomatosis) but was negative with the tumor cells of all preinvasive and most invasive carcinomas. In adenotic and epitheliotic proliferations, groups of cells were identified that reacted strongly with KA1 antibody in addition to antibodies to cytokeratins 18 and 19. The data are discussed with respect to epithelial cell heterogeneity in the breast. We show that by using such antibodies, benign epithelial proliferations are clearly distinguished from carcinomas.
Adenofibroma↗
[Breast reconstruction using a skin expander prostheses following modified radical mastectomy].
In the period from September 1983 to May 1986, 116 breast reconstructions were performed at Heidelberg University Gynecological Clinic with the aid of skin expander prostheses, following modified radical mastectomy (89 primary and 27 secondary reconstructions). In 18% of all cases, complications occurred due to the expanders, the most common being loss of prosthesis material. A total of 82 women have meanwhile had the expander prosthesis replaced by a definitive gel prosthesis in a "second reconstruction phase". Reconstruction of the nipple and areola has been performed in six cases in a third phase. Today, breast reconstruction in one or two stages following modified radical mastectomy represents an integral part of surgical rehabilitation of primarily operable breast cancer in cases, where a primary conservative procedure is out of the question.
Adult↗
[CA 15-3 and CEA as tumor markers in the diagnosis of the recurrence of breast cancer].
The significance of the tumor markers CA 15-3 and CEA for the oncological follow-up of breast cancer was examined in a retrospective analysis of 108 patients in whom, before and after hospitalization, it was possible to locate a local recurrence, a contralateral breast carcinoma, or a distant metastasis. Overall, examination of the group of patients showed that CA 15-3 was significantly more sensitive than CEA (57%/38%), with an increase of only 3% in sensitivity when investigating both markers simultaneously. Neither marker is suitable for the diagnosis of a relapse in the same region or a contralateral breast carcinoma, as pathologic values are only to be observed in one-third or, respectively, one-quarter of all cases. In cases of distant metastasis, CA 15-3 is significantly superior to CEA (osseous: 62%/41%; visceral: 73%/34%). Only where there is combined osseous/visceral metastatic spread is no significant difference manifested (87%/74%). In 15 out of 17 patients with an apparently relapse-free course both during and after hospitalization, the CA 15-3 value was normal where the CEA value was pathologic. Tumor progression would thus seem improbable where there is a pathologic CEA value in conjunction with a normal CA 15-3 value. In follow-up of breast cancer, simultaneously assay of both "nonredundant" tumor markers, which represent a useful spectrum for tumor control, is to be recommended.
Antigens, Neoplasm↗
[Rate of local recurrence and survival in patients with breast reconstruction following mastectomy].
A retrospective study was conducted covering 100 patients who underwent breast reconstruction with plastic prostheses following mastectomy during the period from 1975 to May 1986. They were compared with 100 patients (matched pairs) who had not undergone breast reconstruction. No significant difference between the two groups could be found as regards locoregional recurrences or the overall survival rate. The mean observation period was 86.5 months. Surgical removal of local recurrences did not necessarily involve removal of the prosthesis. Therefore, given adequate operability, and experience on the part of the surgeon, a breast reconstruction following mastectomy can now be performed on any patient desiring it to alleviate mental suffering.
Adult↗
[Therapy with gonadotropin releasing hormone agonists (zoladex) in premenopausal females with metastastic breast cancer].
Medicinal castration using GnRH-analogues is a new therapeutic possibility for treating metastasizing breast cancer in premenopausal women. A total of 22 premenopausal patients were included in the study reported here, all of them low-risk cases. Twenty of the 22 patients had hormone receptor-positive primary tumors. A slow-release depot form of Zoladex (ICI 118630) was used as a GnRH agonist and was administered subcutaneously (3.6 mg) at four-week intervals. The long-term administration of Zoladex brought about a significant reduction in blood FSH, estradiol, and progesterone levels within one to four weeks. In contrast, there were no detectable changes in ACTH, DHEAS, cortisol, testosterone, prolactin, or androstendion levels. Therapy-induced amenorrhea occurred in all cases. The objective remission rate achieved (complete and partial remission) was 45%. As opposed to other formulations, the use of Zoladex as a GnRH analog in depot form has significant advantages, which become particularly evident through improved compliance. With Zoladex therapy an effective drug-induced castration can be accomplished in premenopausal women. As regards its efficacy it is comparable to an ovarectomy, though with less pronounced side effects.
Adult↗
[Transposition and myocutaneous island flaps in primary or secondary locoregional surgical therapy of breast cancer].
New plastic surgical reconstruction techniques can today make a major contribution to locoregional therapy in breast cancer cases. The present paper reports on indications for and experience gathered in primary and secondary therapy with transposition (medial-pedicled thoracoepigastric) and myocutaneous island flaps (lower transversal rectus and latissimus dorsi) at the University Gynecological Clinic of Heidelberg between October 1981 and June 1987. Thirty-nine patients were treated using these techniques. Altogether nine rectus, 13 latissimus dorsi, and 21 thoracoepigastric flaps were used; in 16 cases for primary treatment with T4 tumors and in 27 cases for secondary treatment. In view of the rate of complications and recurrences seen, the indication must be established strictly and individually according to the location of the defect, the anatomic situation, and the prognosis for the patient. Today, the use of these plastic surgery techniques should lie in the hands of experienced surgeons and be an integral part of the treatment of primary advanced breast carcinomas or large locoregional recurrences.
Adult↗
[Flow cytophotometry parameters, hormone receptors and axillary lymph node status as prognostic factors in primary breast cancer].
The prognostic significance of DNA flow cytometric examinations of 247 patients (mean age 57 years; 27-84) with operable breast cancer was analyzed. The findings were compared with biochemically determined steroid-hormone receptors and lymph node status. Forty-two percent of the tumors were diploid and 58% aneuploid; 32% of them had a high S-phase portion (greater than 5%; definition by the crit-level method). S-phase fractions were lower in diploid than in aneuploid tumors (2.5 +/- 2.2% versus 5.5 +/- 3.4%). Both with diploid tumors as well as tumors with a low S-phase fraction (less than 5%), recurrence-free survival was better than with aneuploid tumors (p = 0.02) and tumors with a high S-phase fraction (p = 0.004). A direct proportional relationship was found between the S-phase fraction and the mean recurrence-free interval. As regards overall survival, no significant differences have been detected so far, either for diploid and aneuploid tumors or tumors with low and high S-phase fractions. Using the Cox regression model, the prognostic significance of ploidy status and S-phase, as new factors, independent of age, lymph node and steroid-hormone receptor status, is shown. DNA flow cytometry is suitable for routine clinical use and should be used in particular as an independent prognostic factor for planning and stratification in adjuvant therapeutic studies.
Adult↗
[Gonadotropin-releasing hormone receptors in human breast cancer tissue].
Analogues of gonadotropin-releasing hormone (GnRH) are presently being investigated for the treatment of metastatic breast cancer. Although their effects are thought to be mediated via the suppression of gonadotropins and gonadal steroids, they could possibly also act directly on the tumour. The binding of a GnRH-agonist to membrane fractions of 97 primary human breast carcinomas was investigated. In 43 cases (44%) the presence of specific GnRH receptor binding sites (above 3 fmol/mg membrane protein) was shown. GnRH receptor content was 6.2 fmol/mg membrane protein in estradiol receptor (ER) positive tissues and in ER negative tissues 2.0 fmol/mg membrane protein (p less than 0.05). Progesterone receptor (PR) positive contained 5.2 fmol/mg protein and PR negative carcinoma contained 2.0 fmol/mg membrane protein. In postmenopausal women GnRH receptor concentration was 5.4 and 2.9 fmol/mg membrane protein, respectively, in ER positive and negative tissues (p less than 0.05) whereas 4.4 and 5.2 fmol/mg membrane protein, respectively, in PR positive and negative samples. Binding of GnRH was positive (above 3 fmol/mg protein) in 33% premenopausal and in 54% of postmenopausal cases. Further clinical studies with GnRH analogues will clarify the therapeutic value of GnRH receptor determination in breast cancer.
Binding, Competitive↗
Psammomabody content and DNA-flow cytometric results as prognostic factors in advanced ovarian carcinoma.
138 advanced ovarian serous carcinoma--all FIGO stages III/IV--were investigated by prognostic morphological factors like tumour grading and rate of psammomabody content--subdivided in to serous carcinoma with a high, a moderate and a low rate of psammomabodies and a group of serous carcinoma without psammomabodies. Additionally 91 of these tumours were examined by DNA-flow-cytometry--respectively DNA-ploidy and s-phase-fraction. All prognostic factors were correlated to the overall survival time. The psammomabody content factor is only important if histologically a high or moderate rate of psammomabodies is found in the tumour tissue. Tumours with a low rate of psammomabodies do not differ from serous tumours without psammomabodies. DNA-flow-cytometry is a qualified method to demonstrate a slow tumour growth tendency. The majority of carcinomas with a high rate of psammomabodies is DNA-diploid and has a low -phase-fraction. The overall survival rate for these tumours is much better. Tumour grading--a more subjective method--is also of high value, but there is a certain difficulty in reproducing the results in individual cases. By the combination of the two morphological methods--semiquantitative assessment of psammomabodies and DNA-flow-cytometry--we were able to discover a small group of patients with advanced ovarian cancers who have a favourable prognosis.
DNA↗
Influence of systematic errors on the evaluation of the S phase portions from DNA distributions of solid tumors as shown for 328 breast carcinomas.
The portion of cells in S phase has proved to be a valuable prognostic indicator of early relapse and life expectancy, particularly in breast carcinoma. Comparisons of published data on samples of primary breast carcinoma biopsies showed that the values obtained by analyses of flow cytometric DNA distributions were generally higher than those of determinations based on the tritiated thymidine (3H-ThdR) labeling index (LI). Flow cytometric DNA analyses of 328 biopsy samples of primary breast carcinomas revealed that these differences could be explained by varying contributions of debris background. Since this influence is inversely proportional to the cell counts in each channel, it may cause considerable errors, particularly in the S phase channels, which normally contain the lowest counts of the DNA distributions. Two different mathematical rationales were tested in order to separate DNA distributions from the debris superimposition. No appreciable differences were found with respect to the essential results. After appropriate subtraction of the background levels, the previously reported discrepancies between cytometrically determined S phase portions and 3H-ThdR LI values disappeared, and good agreement was achieved for the comparable tumor samples of the present study. In conclusion, debris background subtractions should generally precede the DNA histogram analyses, particularly of solid tumors, in order to obtain reliable S phase values.
Breast Neoplasms↗
Immunological approach to characterize proacrosin and various acrosin forms in boar and man by monoclonal antibodies.
Three different monoclonal rat antibodies, Acr1, Acr2, and Acr3, have been established against boar proacrosin. They are shown by enzyme-linked immunosorbent and immunoblot assays to react with boar proacrosin and several different acrosin molecules derived therefrom during activation. The epitopes detected by the three antibodies are different from each other, one being highly sensitive to reduction and periodate treatment. The antibodies crossreact with various proacrosin and acrosin molecules derived from human sperm extract; they also show indirect immunofluorescent staining of the acrosomal region of ejaculated sperm from normal men but fail to react with round-headed spermatozoa.
Acrosin↗