SEARCH · PubMed Health

Results for “Endocrine therapy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed1986

Intermittent endocrine therapy for advanced prostate cancer.

Twenty patients with advanced prostate cancer have been treated with an intermittent endocrine therapy schedule. Hormone therapy (diethylstilbestrol in 19 patients and flutamide in 1 patient) was administered until a clinical response was clearly demonstrated and then it was withheld until symptoms recurred. Prior to treatment 17 of 20 patients had bone pain and positive radionuclide scans, two had asymptomatic pulmonary metastases, and one had symptomatic localized disease. Duration of endocrine therapy prior to withdrawal of all treatment ranged 2 to 70 months (median, 10 months). Disease progression occurred 1 to 24 months (median, 8 months) after interruption of therapy. All patients who relapsed had a rapid clinical response following resumption of endocrine therapy. Nine of ten patients rendered impotent by endocrine therapy resumed sexual activity within 3 months of stopping treatment. This data indicates that satisfactory palliation of advanced prostatic cancer can be achieved in selected patients using intermittent endocrine therapy.

Aged↗

PubMed2002

Neoadjuvant endocrine therapy of breast cancer: a surgical perspective.

Neoadjuvant treatment with chemotherapy or endocrine agents is being used increasingly to downstage locally advanced and large operable breast cancers. Following these treatments, inoperable breast cancer often becomes fully resectable, and initially operable tumours requiring mastectomy may be successfully removed by breast-conserving surgery. Patient selection is important to optimise neoadjuvant endocrine therapy: only patients with oestrogen receptor (ER)-rich breast cancer are candidates, and postmenopausal women are likely to benefit the most. Such patients can expect a high probability of responses over a 3-month treatment period. Response to therapy should be monitored by clinical examination as well as by ultrasound, mammography, or other imaging procedures. Third-generation aromatase inhibitors (letrozole, anastrozole and exemestane) are more effective than tamoxifen in this treatment setting. In a large randomised trial of neoadjuvant endocrine therapy in postmenopausal women, letrozole achieved significantly higher response rates than tamoxifen, and a correspondingly higher rate of breast-conserving surgery was possible in the letrozole-treated patients. There is some evidence to suggest that the nature of the tumour response is different for preoperative endocrine therapy compared with chemotherapy. This difference may result in a higher rate of complete tumour excisions following breast-conserving surgery after neoadjuvant endocrine treatment. There appears to be a low rate of subsequent local recurrence in patients having breast-conserving therapy after neoadjuvant endocrine therapy.

Antineoplastic Agents, Hormonal↗

PubMed1990

Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study.

Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease. To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide-Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy. One hundred forty-three patients were registered, and only six were declared ineligible. Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%). A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059). Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease. Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms. Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo-endocrine therapy arm (median survival, 22.0 months). No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model. Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy. Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES. These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer.

Adult↗

PubMed1997

Detection of apoptosis by the TUNEL technique in clinically localised prostatic cancer before and after combined endocrine therapy.

AIMS: Apoptosis in prostate cancer was evaluated after three months of combined endocrine therapy to investigate the association with tumour grade, tumour stage, and the immunohistochemical detection of p53 and bcl-2 in tumour cells before and after therapy. METHODS: Twenty six formalin fixed, paraffin wax embedded core biopsies and corresponding prostatectomy specimens, excised after three months of combined endocrine therapy, were analysed for the presence of apoptotic cells by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method, and for p53 and bcl-2 overexpression by immunohistochemistry. RESULTS: All 26 adenocarcinomas were clinically localised at diagnosis. In biopsies performed before combined endocrine therapy, the apoptotic indices varied between 0.09% and 1.73%, while the tumour grade fell between Gleason score 1 and 8. The mean (SD) apoptotic count pretherapy was 0.71% (0.50). There was a significant association between elevated apoptotic counts and higher Gleason scores in the biopsies (p = 0.005). After three months of therapy, the percentage of apoptotic tumour cells increased independently of tumour stage, while a significant association with Gleason grade was found (p = 0.0018) and all the tumours had Gleason scores of < 7. In eight cases the apoptotic index was more than twice its pretherapy value. The remaining tumours showed less of an increase in the apoptotic index (five cases) or a reduction in the percentage of apoptotic cells. The overall moderate increase in apoptotic index after combined endocrine therapy was not statistically significant (p = 0.8). Immunoreactivity to p53 was absent in all cases, before and after therapy, while a slight increase in the number of cells overexpressing bcl-2 was observed in five of the 13 tumours (38.1%) with reduced apoptotic indices after therapy. CONCLUSIONS: After three months of combined endocrine treatment a minority of clinically localised prostate neoplasms showed regressive epithelial alterations, associated with an increase in apoptotic tumour cells; an increase in cells overexpressing bcl-2 was observed in five of the 13 tumours with reduced apoptotic indices.

Adenocarcinoma↗

PubMed2004

Feasibility of sentinel node biopsy for breast cancer after neoadjuvant endocrine therapy: a pilot study.

BACKGROUND AND OBJECTIVES: Sentinel node biopsy (SNB) is used for evaluation of axillary lymph node status of patients with breast cancer. The usefulness of SNB after neoadjuvant chemotherapy is not established. In addition, SNB after endocrine therapy has rarely been evaluated. We assessed the feasibility of dye guided SNB after neoadjuvant endocrine therapy in comparison with those of SNB after chemotherapy. METHODS: A total of 36 patients subjected to SNB after endocrine therapy alone (n = 16) (tamoxifen, anastrozole or combination of goserelin and tamoxifen) or after chemotherapy (n = 20) (anthracycline and/or taxane) were included. SNB was performed with indigocarmine dye prior to the wide resection of the tumor or mastectomy. RESULTS: Sentinel nodes were successfully identified in 100% (16/16) of patients after endocrine therapy and in 85% (17/20) of patients after chemotherapy. The mean number of harvested sentinel nodes was 2.2 after endocrine therapy and 1.8 after chemotherapy. There was no false negative case after endocrine therapy and there was one false negative case after chemotherapy (8% of overall false negative rate). CONCLUSIONS: SNB seemed feasible and accurate after neoadjuvant endocrine therapy in patients with breast cancer.

Adult↗

PubMed1992

Endocrine therapy for advanced breast cancer: a review.

More than 45,000 women will die of metastatic breast cancer in the United States in 1991. Endocrine therapy remains a major option for treatment of such patients, and results in complete plus partial response rates of 30% with a median duration of approximately one year. Postmenopausal status, increased age, a prolonged disease-free interval, bone and soft tissue metastases, and positive estrogen and progesterone receptors are all associated with an increased response to endocrine therapy. The use of additive hormonal therapy, specifically antiestrogens, progestins, and aromatase inhibitors, have replaced surgical ablative procedures in the majority of patients; response rates to antiestrogen therapy, progestin therapy, and aromatase inhibitors are similar, but antiestrogens have generally been associated with the most favorable therapeutic index. At present, there is no convincing evidence that either combinations of endocrine therapies or endocrine therapy combined with chemotherapy are associated with an improvement in survival for patients with metastatic disease. Future research efforts directed at defining the molecular mechanisms of endocrine activity should facilitate clinical trials of newer and potentially more effective agents. All patients with metastatic breast cancer should be considered for at least one trial of endocrine therapy provided their metastatic disease is not rapidly progressive or life-threatening.

Adrenal Cortex Hormones↗

PubMed2006

Neoadjuvant endocrine therapy for locally advanced breast cancer.

Patients with locally advanced breast cancer are frequently treated with preoperative (neoadjuvant) systemic therapy to downstage the tumor and improve surgical outcomes. The conventional approach has been to administer chemotherapy but for estrogen receptor-positive (ER+) tumors endocrine therapy is a logical alternative. Neoadjuvant endocrine therapy was initially investigated in older or medically frail individuals who were poor candidates for cytotoxic drugs. However, indirect comparisons suggest that preoperative endocrine therapy with an aromatase inhibitor promotes breast conservation probably as frequently as chemotherapy. As a result, primary systemic therapy with an aromatase inhibitor is now being explored in a younger, healthier population. A key advance would be the development of predictive biomarkers so that this treatment can be more confidently incorporated into routine clinical practice. Interestingly, it seems logical that such a test also would identify patients with highly endocrine therapy-responsive tumors that do not derive much benefit from adjuvant chemotherapy. The American College of Surgeons Oncology Group and the Central Clinical Trials Unit recently activated a neoadjuvant aromatase inhibitor trial with these aims in mind. In this review, we outline the rationale for preoperative endocrine therapy, and consider predictive models for endocrine therapy responsiveness in this setting.

Aged↗

PubMed1988

[Chemo-endocrine therapy of advanced breast cancer].

There have been few randomized trials that have shown a significantly longer survival after chemo-endocrine therapy than the chemotherapy or the endocrine therapy alone, although there seem to be rationales for simultaneous combination of the both modalities. Some new strategies that would make the response rate higher as well as obtain a longer survival by means of chemo-endocrine therapy was suggested. At the present time, sequential endocrine therapy to chemotherapy is recommended for the advanced or recurrent breast cancer patients, except for those with larger tumor burden, liver metastasis, rapid growing tumors, and ER-negative tumors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Preoperative endocrine therapy in patients with locally advanced prostate cancer.

Recently, there has been increased interest in the application of preoperative endocrine therapy prior to radical prostatectomy for locally advanced cancer in order to enhance surgical curability and increase survival. Between 1986 and 1993, 40 patients with prostate cancer were given endocrine therapy before radical prostatectomy. Fifteen patients had stage B2 disease and 25 stage C. The median duration of preoperative endocrine therapy was 3.8 months, and all the patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was an average 25.5% (0-71.8%) decreases in the maximal cross-sectional area of the prostate gland as determined by transrectal ultrasonography. Twenty-four of 25 patients with elevated levels of serum prostate-specific antigen (PSA) showed normal values after preoperative endocrine therapy. Evaluation of treatment-related histological effects, divided into three grades, revealed that 17 patients had pronounced, 11 moderate and 12 poor or no regression. Thirteen of the 40 patients (33%) demonstrated pathological downstaging of disease status from the diagnosis made at the initial clinical examination. After a median follow-up period of 36 months (3-100 months), 36 of the 40 patients are disease-free; two died of cancer 43 and 50 months after surgery, respectively. These results suggest that preoperative endocrine therapy may play an important role in the management of locally advanced prostatic cancer.

Adenocarcinoma↗

PubMed1982

Effects of endocrine therapy on steroid-receptor content of breast cancer.

In order to determine the mechanisms of relapse following response to endocrine therapy, we have measured the oestrogen receptor (RE) content of biopsies of breast cancer in patients receiving various types of endocrine treatment. RE content fell in responding (means of 260.2 to 12 fmol/mg protein) and in nonresponding (means of 155.1 to 31.8 fmol/mg protein) patients who had measurable receptor at the start of treatment. Some of these patients, and a further group of responders to endocrine therapy, were monitored until relapse. Tumour biopsies at the time of relapse showed that 10/14 tumour samples contained significant RE (mean of 86.7 fmol/mg protein; range less than 10-271 fmol/mg protein) after successful endocrine therapy. No relationship could be found between RE content and plasma gonadotrophin or steroid-hormone concentration, but the fall in RE content correlated with reduced numbers of tumour cells in the biopsy. These results indicate that relapse following successful endocrine therapy in breast cancer does not appear to be due to the emergence of RE-negative tumour cells. The fall in RE content during response to endocrine therapy may be due to reduced tumour-cell content of the biopsy.

Adult↗

PubMed1983

[Efficacy of chemo-endocrine therapy for recurrent breast cancer].

Recurrent breast cancer can now be treated more effectively with endocrine therapy, combined with chemotherapy. Between April 1977 and March 1982, 127 breast cancer operations were performed at Kumamoto Municipal Hospital; recurrence was found in 13 cases (approx. 10%). Treatment of 7 of these cases with endocrine therapy (mainly Nolvadex, anti-estrogen) combined with chemotherapy resulted in 6 cases showing either complete response (CR) or partial response (PR). The efficacy of chemo-endocrine therapy was obvious when compared with cases without therapy. Further studies on hormone receptors and the establishment of guidelines for chemo-endocrine therapy as post-operative adjuvant therapy are justified.

Adult↗

PubMed2001

Combination endocrine therapy in the management of breast cancer.

Combination endocrine therapy has long been sought after as a means to better treat breast cancer. Agents that suppress estrogen production are given with agents that suppress estrogenic activity at the cellular level. Historically, these combinations have resulted in initial improvements in response rates, but relapse-free and overall survival were not significantly improved. Also, the increased toxicity seen with these regimens was limiting. New endocrine therapies with more potent activity and less toxicity have led to a resurgence of this idea in the management of breast cancer. Complete estrogen blockade has been compared with single-agent treatments in many different settings. The endocrine effects of this type of therapy are intriguing, but apparently do not readily predict a clinical advantage. The combination of an aromatase inhibitor and an antiestrogen, despite pharmacokinetic interactions, may prove to be beneficial. Results from ongoing trials are eagerly awaited to further address this question in postmenopausal breast cancer patients. For premenopausal breast cancer patients the options are more complex. Clinical outcomes with leutinizing hormone releasing hormone (LHRH) agonists plus aromatase inhibitors are limited to very small phase II studies and are not clearly superior to single-agent therapy. Clinical data in the metastatic setting with premenopausal patients favor the use of an LHRH agonist with tamoxifen over the use of an LHRH agonist alone. However, a similar comparison with tamoxifen alone is lacking with only one trial including this as a treatment arm. Adjuvant therapy with this combined endocrine approach (LHRH agonist plus antiestrogen) has been more extensively studied, but lacks crucial comparisons necessary for making complex treatment decisions. Hopefully, through investigative diligence and ingenuity this issue can be adequately understood. However, many exciting new agents are on the horizon that offer hope to further advance the progress made to date although further confounding the questions already answered.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Sequencing of endocrine therapies in breast cancer--integration of recent data.

A wide range of endocrine therapies has demonstrated activity in the treatment of hormone receptor-positive metastatic breast cancer and sequential tumor responses to sequential hormonal therapies are common. However, the optimal sequence of the hormonal therapies has not yet been determined. The selection of endocrine therapies in women with hormone receptor-positive breast cancer is strongly influenced by the menopausal status of the patient. For premenopausal women, tamoxifen alone or combined with ovarian suppression using a luteinizing hormone-releasing hormone (LHRH) agonist - such as goserelin or leuprolide - is an appropriate first-line hormonal therapy. Ovarian ablation or megestrol acetate is an appropriate second-line hormonal therapy for premenopausal women treated with tamoxifen as first-line therapy, or ovarian ablation plus an aromatase inhibitor (AI) or megestrol acetate for women treated with first-line tamoxifen plus an LHRH agonist. For postmenopausal women, the non-steroidal AIs anastrozole and letrozole now represent the preferred first-line hormonal treatment for metastatic breast cancer, based upon both efficacy and toxicity considerations. For second-line therapy in postmenopausal women, a number of options now exist, including tamoxifen, the steroidal AI exemestane, and the new agent fulvestrant. Fulvestrant, a novel estrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, has been demonstrated to be at least as effective as anastrozole in postmenopausal women whose tumors progress on tamoxifen. The establishment of the optimal sequence of the endocrine therapies should offer significant benefits to women with hormone-sensitive metastatic breast cancer.

Antineoplastic Agents, Hormonal↗

PubMed1996

New endocrine therapies for breast cancer.

How do the new endocrine therapies stand up to the aims of modern endocrine therapy outlined in Table 1? We wish to see increased efficacy, decreased toxicity and improved general health in women taking a new agent. None of the new non-steroidal anti-oestrogens have shown unequivocal evidence of improved efficacy in the clinic to mirror their improved profiles over tamoxifen in preclinical studies. We know that toremifene is equivalent to tamoxifen, but we do not have any phase III data from the other four compounds in development. The specific steroidal antioestrogen, ICI 182,780, looks very promising, but is early in its developmental programme. The new aromatase inhibitors are likely to prove equal to tamoxifen or progestagens, but it is disappointing that improved oestrogen suppression has not led, to date, to improved efficacy. No comment can be made about adjuvant or preventative therapy for any of the new agents, although trials are planned for the new aromatase inhibitors in this clinical situation. Currently, the antiprogestins are disappointing and we will need to wait a considerable time for new agents in preclinical testing to reach the clinic. Many of the new agents are associated with decreased toxicity. It is likely that the NSAEs will be equitoxic with tamoxifen. The steroidal antioestrogen looks particularly non-toxic as do the new aromatase inhibitors, and thus we have an advance in terms of reduced toxicity. The effects of the new agents on the uterus, lipids and bone are in the early stages of testing. Raloxifene, ICI 182,780 and the new aromatase inhibitors are expected to have no proliferative effects on the endometrium, but only the new NSAEs are expected to have beneficial cardiovascular and skeletal effects. If the steroidal anti-oestrogens and new aromatase inhibitors become adjuvant therapies of choice, other agents to prevent osteoporosis and cardiovascular events may also have to be administered.

Animals↗

PubMed1979

Elastosis and response to endocrine therapy in human breast cancer.

Response to endocrine therapy in 51 patients with advanced breast cancer was compared with the amount of elastosis in histological sections from their primary tumours. There appeared to be an association between elastosis and response: tumours with no elastosis showed a lower rate of response than those with gross elastosis, indicating that this simple method might provide a useful predictive index for response to endocrine therapy. In addition, tumours with oestrogen-receptor activity (a feature associated with a high rate of response) but with no elastosis were unlikely to respond, suggesting that a combination of the 2 predictive indices might be more valuable than either taken alone.

Breast Neoplasms↗

PubMed2004

Role of endocrine therapy in the neoadjuvant surgical setting.

Most neoadjuvant (preoperative) therapy of breast cancer has involved the use of chemotherapy, but primary endocrine therapy has also been shown to be effective in postmenopausal women with estrogen receptor-positive tumors. Neoadjuvant therapy can reduce tumor volume, permitting surgery for otherwise inoperable tumors or allowing breast-conserving surgery rather than mastectomy for operable tumors. The preoperative treatment setting also allows for assessment and comparison of responses to different agents, which may then be used in the adjuvant therapy setting following surgery. Since tumor biopsies can be obtained before, during, and after preoperative therapy, the relationship between biomarkers and response or resistance to surgery can be investigated. In the Edinburgh Breast Unit, neoadjuvant endocrine therapy with aromatase inhibitors has been more successful than with tamoxifen. Recurrence rates following preoperative endocrine therapy and breast-conserving surgery have been acceptably low, provided that radiation therapy was also administered postoperatively. Both the probability of response to neoadjuvant letrozole or tamoxifen and the degree of tumor shrinkage increased as estrogen receptor expression increased, consistent with the results of other studies. Attempts to identify biomarkers of response to neoadjuvant endocrine therapy are under way, with early indications that reduced cell proliferation 14 days after initiation of treatment correlates with responses to tamoxifen.

Antineoplastic Agents, Hormonal↗

PubMed2005

Fulvestrant ('Faslodex'): extending the reach of endocrine therapy?

An effective option for estrogen receptor-positive breast cancer, endocrine therapy has had a significant role in improving the survival of women with postmenopausal breast cancer for more than 20 years. However, acquired resistance to disease by cancer cells is the repeated cause of relapse for patients. This supplement explores current thinking on resistance to endocrine therapy and, in particular, the potential role for fulvestrant ('Faslodex'), a novel endocrine therapy that possesses a unique mechanism of action.

Antineoplastic Agents, Hormonal↗

PubMed1998

[Endocrine therapy for prostate cancer in the future].

Endocrine therapy for prostate cancer has been changing rapidly. While LH-RH agonists have been popularly used in medication, their long-acting sustained release formulation is about to be introduced to clinics in Japan. LH-RH antagonists, which have not attracted much attention of clinicians because of adverse reactions, are also going to be put into practical use in the near future. Bicalutamide, which is considered to have greater usefulness than other anti-androgens, is now under regulatory review by the authorities for approval. In addition, a broader range of endocrine therapies is being studied for treatment of prostate cancer. In terms of treatment methods, a number of attempts are made in selection of subject patients, treatment timing, combination treatment and so on.

Adult↗