[Immunohistochemical detection of nuclear estrogen receptors with monoclonal antibodies in different types of breast cancer].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W Jonat.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The results of preliminary investigations into specific immunohistochemical detection of the estrogen receptor in breast cancer tissue by means of monoclonal antibodies are presented. Thirty-one tumor tissue samples stored in a tumor tissue bank for between 10 and 35 months were immunohistochemically studied. The comparison between the immunohistochemical result and the result of the biochemical estrogen receptor assay show a large measure of agreement (90%). The comparison of the results with regard to response to endocrine therapy in cases of metastatization shows that immunohistochemical detection furnishes at least as much information as the dextran-coated charcoal method.
A variety of test systems have been developed for predicting the efficacy of cytotoxic drugs in the treatment of individual malignant human tumors. The present paper reports on the author's experience with Volm's short-term chemosensitivity test and Hamburger and Salmon's stem-cell assay. In the Volm test the influence of adriamycin on the incorporation of radioactively labelled uridine in an individual tumor cell suspension was investigated. Comparison with a cytostatic-free control permitted conclusions to be drawn with regard to the proliferation-related chemosensitivity. The stem-cell assay is based on the capacity of certain tumor cells, the so-called stem cells, to form colonies in a bilaminar soft agar system. The growth of the colony of pre-incubated cytostatics was evaluated in relation to that of untreated tumor cells. The Volm test was successful in 63 (95%) out of a total of 66 tests conducted. Twelve tumors were chemosensitive in the test and 51 chemoresistant. In the stem-cell assay, growth of a colony which permitted chemosensitivity to be tested was only found in 27 out of 183 tests. The criterion of chemosensitivity with a reduction of at least 50% in the number of cells in the colony by at least one cytostatic was satisfied by 14 (29%) of the 49 stem-cell assays which could be evaluated, there being no differences between breast and ovarian carcinomas. The two test systems indicated the chemosensitivity correctly in less than 50% of 49 retrospectively evaluated courses of disease. In contrast, resistance was predicted correctly in 90%.(ABSTRACT TRUNCATED AT 250 WORDS)
Estrogen receptors are detectable in an average of 64.5%, progesterone receptors in 49.7% of patients with ovarian carcinoma. But these receptors can also be found in normal ovarian tissue. Response rates of hormonal therapies between 0 and 38% are found in 8 published papers. This corresponds to a mean response rate of 16.5%. Remission rates of 4 to 15% are to be expected under high-dose gestagen therapy. It would seem that hormonal drugs should be applied to improve the general condition and due to psychological reasons.
The determination of hormone receptors is an accepted tool for predicting response to endocrine therapy in advanced breast cancer. Moreover, hormone receptors have a certain prognostic value for the disease-free interval and overall survival time. In our department we have analysed nearly 5,000 breast cancer tissue samples for oestrogen and progesterone receptors. On the basis of our results and data from the literature the following questions, of particular importance to oncologists, are discussed: Which patients possess hormone receptors? Do therapeutic measures influence hormone receptors? Do hormone receptors have a prognostic value for the disease-free interval? What clinical value do hormone receptors have in advanced breast cancer?
High-dosage medroxyprogesterone (Farlutal, 1 g/d orally) was administered to 42 female patients with progressive disseminated carcinomas of the breast after conventional cytostatic and hormonal treatment had failed. Besides evaluation of success of treatment the pharmacokinetics of medroxyprogesterone were investigated. A remission rate of 37% (total and partial remissions) indicated that high-dosage oral treatment with gestagens can be used as "failure-regime" in patients at the end of conventional treatment. The plasma level of the gestagen approached values corresponding to high-dosage intramuscular application.
This pilot study includes 115 consecutive patients admitted in the period from 1978 to 1981. Patients eligible for this study were at high risk according to the TNM classification with stages pT1-pT3 and pN+, MO. Primary therapy included modified radical mastectomy and axillary-node clearance, one or more ipsilateral nodes being involved in routine histology. All tumors were assayed for estrogen and progesterone receptors. According to the result of the estrogen receptor assay, estrogen-receptor-positive patients were treated with Tamoxifen 30 mg/day for a period of 2 years. Estrogen-receptor-negative patients were treated with cytoxan, methotrexate, and 5-fluorouracil or adriblastin, cytoxan. After a median observation time of 36 months, overall there have been 31 recurrences: 9 = 17.3% in the estrogen-receptor-positive group and 22 = 34.9% in the estrogen-receptor-negative group. The analysis of different subgroups showed no significant differences, either in relation to axillary lymph-node status or in relation to menopausal status in the endocrine-treated compared with the polychemotherapy group. This result suggests, especially in the subgroup of patients with involvement of one to three axillary nodes, that estrogen-receptor-positive and estrogen-receptor-negative patients should be considered as separate groups when adjuvant therapy is indicated. Possibly hormone-receptor-positive patients may benefit from endocrine therapy and do not need polychemotherapy.
Adjuvant chemotherapy should be conducted at present only under controlled conditions ("studies") with the consent of the patient after supplying her with adequate information ("informed consent"). The most important prognostic factor in primary carcinoma of the breast is the axillary lymph node status. The decisive role with regard to determining the further course of action and mapping out the treatment strategy will be played by the operating surgeon and the pathologists. Adjuvant chemotherapy can prolong the relapse-free survival time for all prognostic sub-groups known so far (the differences, however, are not significant in every case). It is very probable that the total survival rate will be improved for certain sub-groups. The effectivity of adjuvant chemotherapy decreases with increasing involvement of the lymph nodes. Pre-menopausal patients with one to three affected lymph nodes presently derive the biggest benefit from adjuvant chemotherapy. Short-term chemotherapy (up to 6 months) will suffice. The optimal treatment period is not yet known. The aggressivity of the adjuvant chemotherapy chosen for a particular case is of absolutely paramount importance. Provided the dosage is the same for both groups, there is no evidence of any clear difference between pre-menopausal and post-menopausal patients. It seems, however, that the quantitative reduction of the relapse rate is greater with pre-menopausal patients. Onset of chemotherapy should be as early as possible after surgery (14th postoperative day). A dosage schema should be followed according to calculated full dosage, if possible via the intravenous route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This paper gives a review of the historical development of endocrine treatment procedures of breast cancer patients. Compared with the chemotherapy endocrine therapies have less side effects and are less expensive. On the other hand, the remission rates in unselected patients are in the range of 30% only. The determination of steroid hormone receptors at present is the best method for selection of the patients. The remission rates in patients with estrogen receptor positive tumors are 50-60%, with additionally progesterone receptor presence up to 77%. Patients lacking receptors in their tumor tissue have a little chance [5 (-10) %] of responding to an endocrine measure. This is true for ablative (ovariectomy, adrenalectomy, hypophysectomy) as well as for additive procedures (estrogens, androgens, antiestrogens).
The determination of hormone receptors in tumor tissue samples today is accepted as a necessary step with in a selective treatment plan for patients with breast cancer. The following way discussed our clinical knowledge about hormone receptors in breast cancer. Besides a therapy concept for metastatic breast cancer an adjuvant treatment trial for stage II breast cancer patients based on the estrogen receptor status will be presented.
In a retrospective study, response to systemic polychemotherapy was analyzed in 72 female patients having advanced breast cancer and correlated with estrogen receptor (ER) status. Estrogen receptors were analyzed by agar-gel electrophoresis or uptake competition technique in tumor biopsy specimens derived from the primary tumor or from metastases. The borderline between positive and negative ER values was declared to be 20 fmol/mg tissue protein. Most of the patients have had an extramural review. We did not find statistically significant differences between the ER-positive (ER+), and ER-negative (ER-) groups in these characteristics: age; menopausal status; disease-free interval; dominant site of involvement. Chemotherapy regimens utilized in the two groups were comparable. According to criteria formulated by the European Organization on Research and Treatment of Cancer (EORTC), there is no evidence that response to chemotherapy is correlated with the presence or absence of estrogen receptor. Thirteen of 31 ER+ patients responded objectively to chemotherapy (42%) and 17 or 41 ER- patients gained such remission (41%). Given the retrospective nature of the data, this result should be interpreted cautiously. More clinical studies are warranted to determine whether response to cytotoxic agents is affected by ER status.
Patients with advanced breast cancer and low or poor concentration of estrogen receptors in tumor biopsies have little chance of responding to endocrine therapy. This problem was seen in a group of nonresponding estrogen receptor-positive (ER+) patients. Some comments on possible explanations for this phenomenon are made and suggestions to overcome it are given.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.