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PubMed2006

Neoadjuvant endocrine therapy in breast cancer.

The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outside of the elderly population. The wider use of aromatase inhibitors (AIs) has encouraged studies that compare the efficacy of AIs with tamoxifen in the neoadjuvant setting, but there remains a lack of comparison of neoadjuvant with adjuvant endocrine therapies. This review discusses the current evidence regarding primary endocrine therapy, along with the factors involved in choosing appropriate patients for neoadjuvant therapy and the current opinions on length of treatment time and measurement of response prior to surgery.

Antineoplastic Agents, Hormonal↗

PubMed2005

[Clinical significance of adjuvant endocrine therapy in treatment of endometrial carcinoma: study of 171 patients].

OBJECTIVE: To study the effectiveness of adjuvant endocrine therapy on the prognosis of endometrial carcinoma and to analyze the influence of progesterone receptor on the curative effect of adjuvant endocrine therapy. METHODS: A retrospective study was carried out on 171 patients of endometrial carcinoma with similar pathological examination. 82 of the 171 patients with endometrial carcinoma (48.0%), aged (57 +/- 9) years, underwent endocrine therapy, mainly by progesterone (245 +/- 51) mg/d for (1.3 +/- 0.9) years. 55 cases (67.1%), aged (57 +/- 10) years, underwent endocrine therapy for more-than-one-year (more-than-one-year subgroup), and 27 cases (32.9%), aged (59 +/- 9) years, underwent endocrine therapy for less-than-one-year (less-than-one-year subgroup). 24 of the 82 patients (29.3%) underwent adjuvant radiotherapy. 89 of the 171 patients (52.0%), aged (57 +/- 11) years, were in the control group 31 of the 89 patients in the control group (34.8%) underwent adjuvant radiotherapy, and 39 patients (43.8%) underwent adjuvant endocrine therapy. Follow-up was performed by correspondence, phone call, or outpatient department visit for 3 approximately 4 years. RESULTS: The rate of recurrence and/or metastasis of the endocrine therapy group was 13.4%, not significantly different from that of the control group (23.6%, P > 0.05); the death rate of the endocrine therapy group was 12.2%, not significantly different from that of the control group (20.2%, P > 0.05). The rate of recurrence and/or metastasis of the less- than-one-year subgroup was 25.9%, significantly higher than that of the more-than-one-year subgroup (7.3%, P = 0.012); the death rate of the less- than-one-year subgroup was 22.2%, significantly higher than that of the more-than-one-year subgroup (7.3%, P = 0.036). Cox regression showed that stage, the operation, tumor cell differentiation, and duration of endocrine therapy significantly affected the recurrence/metastasis remarkably (OR = 5.199, OR = 0.507, OR = 1.796, OR = 0.538) and the death rater (OR = 5.488, OR = 0.482, OR = 1.516, OR = 0.547). The rate of recurrence/metastasis of the endocrine therapy group patients with positive progesterone receptor was 4.7%, significantly higher than that of the patients with negative progesterone receptor (26.7%, P = 0.034). CONCLUSIONS: The prognosis of endometrial carcinoma patients can be improved with adjuvant endocrine therapy, especially for those with positive progesterone receptor. Endocrine therapy should be continued no less than 1 year.

Aged↗

PubMed1992

[Recent progress of endocrine therapy in breast cancer].

Recent progresses of endocrine therapy for advanced and early breast cancer was reviewed. The mechanism (s) of an antiestrogen, tamoxifen has been noted at least partly as a stimulation of TGF beta action in ER-positive breast cancer cells. The Early Breast Cancer Trialists' Collaborative Group (EBC TCG) has recently reported the effectiveness of endocrine therapy, oophorectomy for premenopausal patients, and tamoxifen for pre- and post-menopausal patients in the adjuvant treatment for operable breast cancer patients. Two kinds of newly developed endocrine therapy were mentioned; LH-RH analogues for premenopausal patients, and aromatase inhibitors for postmenopausal patients. These agents decrease the plasma estrogen levels, acting like the ablative surgery, and make us more comprehensive combinations of endocrine therapy of breast cancer.

Aromatase Inhibitors↗

PubMed1985

[Endocrine therapy of recurrent breast cancer].

The present status of endocrine therapy in the treatment of recurrent breast cancer was reviewed. Only one third of breast cancer responds to the endocrine therapy, and suitable patients should be selected the treatment. By means of estrogen receptor (ER), it is possible to select ER(-) patients who do not respond to therapy (response rate less than 10%) while 50-60% of ER(+) breast cancer patients respond to therapy. However, this is still unsatisfactory as 50-60% of recurrent breast cancer cases respond to combination chemotherapy. By adding to the ER status certain clinical parameters such as disease-free interval, metastatic site, and performance status, a better response would be obtained with endocrine therapy. The combination of chemotherapy with endocrine therapy would be expected to increase the probability of patient response. According to our prospective randomized trial, however, as well as other reported trials, the survival of patients treated with simultaneous chemo-endocrine therapy has not been prolonged as compared with those who had been treated sequentially with either therapy alone. This suggests that new therapeutic strategies will be necessary in the treatment of recurrent breast cancer.

Adrenalectomy↗

PubMed2004

Overcoming endocrine therapy resistance by signal transduction inhibition.

Endocrine therapy is the most effective systemic treatment for patients with hormone-receptor-positive (HR(+)) breast cancer. Unfortunately, efficacy is often limited by the onset of resistance, which is almost inevitable for patients with advanced disease. Several patterns of endocrine resistance are recognizable clinically, including: A) tumors that are inherently insensitive to all attempts at estrogen receptor (ER) targeting despite expression of ER (pan-endocrine therapy resistance); B) tumors that are estrogen dependent but resistant to one or more specific endocrine therapies (agent-selective resistance); and C) tumors that initially respond but subsequently progress (acquired resistance). Current insights into the molecular basis for these resistance patterns are rudimentary, but are most clearly illuminated by investigations that focus on the crosstalk between the ErbB or HER peptide growth factor family and the ER. The data are sufficiently compelling to be addressed by ongoing clinical trials that examine combinations of endocrine agents and either trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA) or ErbB-specific tyrosine kinase (TK) inhibitors. Preliminary data from a small "proof of concept" phase II study of letrozole (Femara; Novartis Pharmaceuticals Corporation; East Hanover, NJ) and trastuzumab demonstrated durable responses despite tamoxifen (Nolvadex; AstraZeneca Pharmaceuticals; Wilmington, DE) resistance. Efficacy was variable, however, despite the selection of patients on the basis of ER and ErbB-2 coexpression. Complicating matters further, resistance often occurs in the absence of any evidence for ErbB TK family member expression. In the absence of a clear target, common downstream signal transduction proteins that are known to intersect with the ER pathway can be inhibited to address resistance, including G proteins with farnesyltransferase inhibitors and molecular target of rapamycin (mTOR) with rapamycin analogues. With a number of phase III clinical trials now under way, major advances in the endocrine treatment of advanced disease are possible.

Alkyl and Aryl Transferases↗

PubMed2005

[Prognostic factors for PSA relapse of prostate cancer after endocrine therapy].

PURPOSE: Advanced prostate cancer responds well to endocrine therapy initially, but soon becomes refractory and has a poor prognosis. We analyzed the prognostic factors of prostate cancer responding well initially to endocrine therapy with lowering of serum prostate specific antigen (PSA) level but later showing PSA relapse. MATERIALS AND METHODS: In prostate cancer patients newly diagnosed from January 1992 to December 2004 at our institution, there were 93 patients in that the PSA level of 10 ng/ml or more before therapy initially dropped below 10 ng/ml by endocrine therapy, but showed PSA relapse thereafter. We investigated the relationship between clinical stage, pathological differentiation, initial PSA, duration between initiation of therapy and PSA nadir, the value of PSA nadir, duration between initiation of therapy and PSA relapse, PSA doubling time (PSA-DT) at relapse, PSA response three months after initiation of second line therapy and prognosis after PSA relapse. RESULTS: In Kaplan-Meier method, between all or some categories investigated showed significant difference in prognosis after PSA relapse. In multivariate analysis, the factors that significantly affected prognosis after PSA relapse were clinical stage, pathological differentiation, PSA nadir value, duration between initiation of therapy and PSA relapse and PSA response three months after initiation of second line therapy. CONCLUSION: We investigated the prognostic factors refractory to endocrine therapy. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and families.

Aged↗

PubMedDate not supplied

Preoperative endocrine therapy for older women with breast cancer: renewed interest in an old idea.

BACKGROUND: Tamoxifen as sole therapy (primary tamoxifen therapy) was investigated in the 1970s and 1980s as an alternative to surgery for older patients with breast cancer. While the majority of primary breast tumors responded to tamoxifen, long-term local disease control was poor. The use of primary tamoxifen therapy is therefore restricted to frail, elderly, and infirm patients who cannot tolerate surgery. In contrast, short-term preoperative endocrine therapy to downstage estrogen receptor-positive (ER+) tumors is under increasing scrutiny as a nontoxic neoadjuvant approach for older women. METHODS: The literature on primary tamoxifen therapy and preoperative endocrine therapy was reviewed to construct an opinion piece on the feasibility and safety of preoperative endocrine therapy. RESULTS: A review of nine phase II trials and a meta-analysis of two randomized trials suggest that the initial response rates to preoperative endocrine therapy will exceed 50% to 60% for patients with ER+ disease. A short delay in surgery to administer 3 to 4 months of preoperative endocrine therapy is unlikely to compromise long-term outcomes. CONCLUSIONS: Preoperative endocrine therapy is a logical approach for older patients with ER+ disease as a well-tolerated means to increase the rate of breast-conserving surgery. Several clinical trials comparing tamoxifen with selective aromatase inhibitors in the preoperative setting have been conducted, and the results are expected soon. These studies will determine if a large multicenter national trial of preoperative endocrine therapy should be conducted.

Aged↗

PubMed2000

Predictive factors for response to endocrine therapy in patients with recurrent breast cancer.

Predictive markers and variables for response to anticancer therapy provide cancer patients with refinement of therapeutic options and a decreased likelihood of receiving an ineffective therapy. The best-established predictive marker for response to endocrine therapy for breast cancer is the status of estrogen receptors (ER) in the primary breast tumor. However, although patients with ER-positive tumors have a greater than 50% objective response rate to endocrine therapy, other patients can not obtain an objective response. Therefore additional markers, such as better molecular biologic markers, are needed. Our previous study using multivariate analysis revealed that the ER status of primary tumors and the dominant site of metastasis are independent predictors for response to first-line endocrine therapy and that a response to first-line endocrine therapy is only an independent predictor for response to second-line endocrine therapy. However, all these factors are already well-established predictive markers for response to endocrine therapy. Recently, a number of new hormonal agents, such as more selective aromatase inhibitors and specific antiestrogens, have been developed and introduced. However, several questions, such as the best sequences when using hormonal agents, remain to be elucidated. On the other hand, several molecular biologic markers predicting response to endocrine therapy, such as the expression of the HER family of tyrosine kinase receptors, pS2, Bcl-2, and vascular endothelial growth factor, have been reported. To elucidate the most effective use of endocrine therapy for recurrent breast cancer, classical and new predictive factors for response to endocrine therapy are reviewed, and the clinical implications of these factors are discussed.

Antineoplastic Agents, Hormonal↗

PubMed1985

[Results and limits of endocrine therapy of carcinoma of the breast].

This review of endocrine therapy in breast carcinoma has been prepared principally with the aim of listing many persisting controversies in this area, even if significant advances have been made after the hormone receptor determination became available. Endocrine treatments include those indicated in an adjuvant setting and in metastatic disease. Indications for adjuvant endocrine therapy are still uncertain, even if a better selection of patients and the use of a non-toxic drug such as tamoxifen made more rationale and safer this type of treatment. Uncertainty is related to some doubts concerning consistency of survival advantages and to the relationship between advantages possibly obtainable by endocrine therapy or by adjuvant cytotoxic chemotherapy. Endocrine therapy can be cautiously combined with chemotherapy in amy adjuvant setting, as detrimental effects have been reported in some subsets of patients. Indications for endocrine treatment are mostly related to advanced disease, where more favourable results can presently be obtained through a better selection of patients and by less toxic hormone manipulations which are now available. In advanced disease, a sequential use of endocrine therapy and chemotherapy, or vice versa, is preferable to a concurrent administration of both types of treatment. Only some particular clinical situations suggest the latter type of approach. Some uncertainties are still present about the criteria by which, in the sequence, priority should be given to either therapeutic modality.

Biopsy↗

PubMed2003

Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer.

BACKGROUND: Both chemotherapy and endocrine therapy can be used as treatments for metastatic breast cancer. OBJECTIVES: To review the evidence and determine whether chemotherapy or endocrine therapy has the most beneficial effect on treatment outcomes (survival, response rate, toxicity and quality of life). SEARCH STRATEGY: The specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 16th September 2002 using the codes for "advanced breast cancer", "chemotherapy" and "endocrine therapy". Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library. SELECTION CRITERIA: Randomised trials comparing the effects of chemotherapy alone with endocrine therapy alone on pre-specified endpoints in metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Data were collected from published trials. Hazard ratios were derived for survival analysis and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present. MAIN RESULTS: The primary analysis of overall effect using hazard ratios derived from published survival curves involved six trials (692 women). There was no significant difference seen (HR=0.94, 95%CI 0.79-1.12, p=0.5). A test for heterogeneity was p=0.1. A pooled estimate of reported response rates in eight trials involving 817 women shows a significant advantage for chemotherapy over endocrine therapy with RR=1.25 (1.01-1.54, p=0.04). However the two largest trials showed trends in opposite directions, and a test for heterogeneity was p=0.0018. There was little information available on toxicity and quality of life. Six of the seven fully published trials commented on increased toxicity with chemotherapy, mentioning nausea, vomiting and alopecia. Three of the seven mentioned aspects of quality of life, with differing results. Only one trial formally measured quality of life, concluding that it was better with chemotherapy. REVIEWER'S CONCLUSIONS: In women with metastatic breast cancer and where hormone receptors are present, a policy of treating first with endocrine therapy rather than chemotherapy is recommended except in the presence of rapidly progressive disease.

Antineoplastic Agents, Hormonal↗

PubMed2006

p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer.

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. MATERIALS AND METHODS: The expression of HER2, p53, and Ki67 was examined by immunohistochemistry in primary breast tumour specimens from 73 metastatic breast cancer patients who received first-line treatment with endocrine therapy on relapse, and analysed to determine whether expression of these molecular markers affected the response to endocrine therapy. RESULTS: Of the 73 invasive ductal carcinomas, 12.3%, 21.9%, and 35.6% were positive for HER2 overexpression, p53 protein accumulation, and Ki67 expression, respectively. All patients received endocrine therapy as first-line treatment for metastatic breast cancer; 34 patients (46.6%) responded. Patients with primary breast tumours that had p53 protein accumulation and Ki67 expression showed significantly more resistance to endocrine therapy (P = 0.0049 and P = 0.024, respectively). There were also tendencies for HER2 overexpression to correlate with resistance to endocrine therapy, but this did not reach significance. p53 protein accumulation and HER2 overexpression significantly reduced post-relapse survival (P < 0.0001 and P = 0.001, respectively), and these factors were also statistically significant in a multivariate analysis. CONCLUSION: These data suggest that p53 protein accumulation is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in hormone receptor-positive metastatic breast cancer.

Adult↗

PubMed1997

Predictors of response to second-line endocrine therapy for breast cancer.

This study reports on factors predicting response to second-line endocrine therapy in 250 patients with breast cancer for which they were assessable for response by the International Union Against Cancer (UICC) criteria. Clinical details relating to first-line endocrine therapy were available for all patients. We have not included in this study patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy--e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, or remained in long-term remission on first-line endocrine therapy. One hundred and fifty nine patients (72%) achieved remission (objective response and static disease [OR + SD]) on first-line endocrine therapy with a median duration of 19 months. For second-line endocrine therapy the remission rate was 53% (132/225) with a median duration of 15 months. Tumour grade and oestrogen receptor status of the primary tumour were shown to be independent predictors of response to second-line endocrine therapy while response to first-line endocrine therapy was a predictor of the duration of response to second-line endocrine therapy. In the sub-group of patients who showed OR or SD to both first and second-line therapies, there was no correlation between the time to progression (TTP) on first and second-line therapies.

Adult↗

PubMed1998

Update on endocrine therapy for breast cancer.

The choice of endocrine agent for breast cancer depends on the menopausal status of the patient, the stage of disease, prognostic factors, and the toxicity profile of the agent. Endocrine therapies are typically given sequentially, with the least toxic therapy given first. Tamoxifen is considered first-line endocrine therapy for all stages of breast cancer. New antiestrogens in development include nonsteroidal agents related to tamoxifen and pure steroidal antiestrogens. Luteinizing hormone-releasing hormone agonists are an effective form of endocrine therapy for premenopausal women with advanced breast cancer, and aromatase inhibitors are effective in postmenopausal women. Newer and more selective aromatase inhibitors that are p.o. active and have improved side-effect profiles have been developed. Recent trials have found these agents to improve survival in comparison to the progestins; thus, aromatase inhibitors are replacing progestins as second-line therapy for metastatic disease. Current trials are examining the potential role of aromatase inhibitors as first-line therapy for metastatic disease or as adjuvant therapy for early disease. The antiprogestins and antiandrogens studied thus far have had only limited success in breast cancer clinical trials.

Antineoplastic Agents, Hormonal↗

PubMed2001

Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer.

BACKGROUND: Long-term results were analyzed to evaluate the role of endocrine therapy in the management of local and distant recurrence of prostate cancer following external radiation therapy. METHODS: Between 1976 and 1994, 92 patients with untreated prostate cancer underwent external beam radiation therapy alone. Endocrine therapy had been started when relapse was evident. RESULTS: Failure was seen in 35 of 92 patients: 10 local, 19 distant and six biochemical failures. Endocrine treatment was performed in 28 patients with nine local and 19 distant failures. The cancer-specific survival rate from the endocrine treatment was 54.5% at 5 years. Prostate-specific antigen level in 20 of 20 patients (100%) decreased to below the normal limit 3 months after the start of endocrine therapy. In univariate analysis, T classification was the most significant variable for cancer-specific survival from the initial treatment. CONCLUSIONS: A favorable outcome was achieved by endocrine therapy in patients who had relapsed after external beam radiation monotherapy. Even the recurrent tumor had a sensitivity to androgen. Patients with locally advanced disease (T2b and T3) had poorer prognosis than those with minimally extended disease (T1b and T2a).

Aged↗

PubMed2003

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy.

PURPOSE: This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant ('Faslodex'). PATIENTS AND METHODS: A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting > or = 24 weeks, or disease progression. RESULTS: Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in > 80% of patients. CONCLUSIONS: After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required.

Adult↗

PubMed2006

Estrogen receptor pathway: resistance to endocrine therapy and new therapeutic approaches.

Endocrine therapy is widely accepted as the most important treatment for all patients with hormone receptor-positive breast cancer. However, despite the positive effect of endocrine therapy on clinical outcome, resistance to these drugs inevitably develops. This article reviews the problem of resistance to hormonal therapy and addresses potential approaches to overcome intrinsic or acquired mechanisms of resistance.

Antineoplastic Agents, Hormonal↗

PubMed2003

[Clinical study of endocrine therapy in stage B and C prostate cancer].

To evaluate the usefulness of endocrine therapy for stage B and C prostate cancer, we carried out a retrospective study on overall survival rate, cause-specific survival, PSA recurrence-free rate, and their predictive factors in 118 patients with stage B prostate cancer, 61 with stage C prostate cancer who underwent endocrine therapy at our department between 1985 and 2001. The cause-specific survival rate and PSA recurrence-free rate of stage B patients who underwent endocrine therapy were well, and they will take a good clinical course. Thus, in this stage of prostate cancer, aged patients and patients with complications may be good candidates for endocrine therapy. The cause-specific survival rate and PSA recurrence-free rate in the stage C patients who underwent endocrine therapy were significantly low. In stage C patients, endocrine therapy should be combined early with other methods such as radiotherapy. In the stage B patients who underwent endocrine therapy, PSA and Gleason score appeared to be associated with the cause-specific survival rate and PSA recurrence-free rate.

Aged↗

PubMed2005

Phosphorylation of estrogen receptor alpha serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer.

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone-receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and crosstalk between ER and other growth factor signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. METHODS: Using immunohistochemical techniques, we focused on the expression and phosphorylation of hormone receptors themselves and examined the phosphorylation of ER-alpha Ser118 and ER-alpha Ser167 and the expression of ER-alpha, ER-beta1, ER-betacx/beta2, progesterone receptor (PR), PRA, and PRB in the primary breast carcinomas of 75 patients with metastatic breast cancer who received first-line treatment with endocrine therapy after relapse. RESULTS: Phosphorylation of ER-alpha Ser118, but not Ser167, was positively associated with overexpression of HER2, and HER2-positive tumors showed resistance to endocrine therapy. The present study has shown for the first time that phosphorylation of ER-alpha Ser167, but not Ser118, and expression of PRA and PRB, as well as ER-alpha and PR in primary breast tumors are predictive of response to endocrine therapy, whereas expression of ER-beta1 and ER-betacx/beta2 did not affect response to the therapy. In addition, patients with either high phosphorylation of ER-alpha Ser167, or high expression of ER-alpha, PR, PRA, or PRB had a significantly longer survival after relapse. CONCLUSION: These data suggest that phosphorylation of ER-alpha Ser167 is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in metastatic breast cancer.

Amino Acid Sequence↗