Years Of Adjuvant Tamoxifen Therapy Research Articles

Clinical factors of the risk of hyperplastic endometry processes on tamoxifen therapy with breast cancer: Retrospective population study

Background. One of the main stages of the treatment of breast cancer (BC) is endocrine therapy with tamoxifen or aromatase inhibitors. Five years of adjuvant tamoxifen therapy reduces the risk of disease recurrence by 39%. Tamoxifen was approved by the U.S. Food and Drug Administration in 1977 as a treatment for ER-positive BC. However, sometime after the start of tamoxifen's wide use, reports have been published on its long-term adverse effects. Most common were hot flashes, gynecological symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep changes, weight gain, and decreased libido. However, more serious adverse events such as venous thromboembolic disease and endometrial hyperplasia or cancer are the most clinically significant. The article presents the results of a retrospective population-based study on assessing hyperplastic processes of the endometrium (HPE) in patients with breast cancer during TAM therapy, conducted in 2017, approved by the Ethics Committee of the Scientific Research of the Russian Medical Academy of Continuing Professional Education. Aim. To identify clinical factors that may increase the risk of HPE during tamoxifen therapy in patients with a history of breast cancer living in the Moscow region. Materials and methods. We retrospectively reviewed 230 case histories of patients with breast cancer. Of these, 120 patients who received TAM therapy had the following HPE risk factors: average age, menopausal status, body mass index, and duration of TAM therapy. Results. It was found that patients with HPE taking TAM were older (p=0.017), more likely to be postmenopausal (p=0.035), overweight (p=0.023), and received TAM for a longer period (p=0.028) than patients without HPE. Conclusion. The data obtained indicate the need for continuous monitoring by gynecologists of patients with breast cancer taking tamoxifen, paying particular attention to women from high-risk groups, namely older postmenopausal women with high body mass index receiving TAM for more than 1.52 years.

Switching to anastrozole plus goserelin vs continued tamoxifen for adjuvant therapy of premenopausal early-stage breast cancer: preliminary results from a randomized trial.

PurposeTo assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2–3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years.Patients and methodsHormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2–3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2–3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events.ResultsA total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3–4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group.ConclusionFor early-stage breast cancer patients who remain premenopausal following 2–3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment.Trial RegistrationClinicalTrials.gov (identifier NCT01352091).

Extending Aromatase Inhibitor Therapy for Early Breast Cancer

In an earlier trial, administration of the aromatase inhibitor (AI) letrozole for 5 years — after about 5 years of adjuvant tamoxifen therapy —

Doubling up?

A study reports the benefits of 10 years of adjuvant tamoxifen therapy for ER-positive breast cancer.

Correlation of Oncotype DX Recurrence Score with Cyclin D1 and ErbB2.

Abstract Background: The Oncotype DX assay predicts the risk of recurrence in patients with stage I-II ER+, node negative breast cancer treated with tamoxifen. It is not understood if the Oncotype DX assay predicts the natural aggressiveness of an individual breast cancer or if it identifies a subtype of tamoxifen resistant breast cancer. In clinical practice, a high recurrence score (RS) on Oncotype DX is interpreted as a more aggressive tumor and is used to justify the use of chemotherapy. However, if the RS was actually predictive of tamoxifen resistance, patients may benefit from the use of an aromatase inhibitor, and chemotherapy may be unnecessary. Cyclin D1 and ErbB2 are two biomarkers shown to predict tamoxifen resistance.Cyclin D1 is overexpressed in approximately 35% of breast cancers. The Austrian Breast and Colorectal Cancer Study Group assessed expression of Cyclin D1 in patients taking tamoxifen within the ABCSG trial 05 and ABCSG trial 06. In both trials, Cyclin D1 overexpression correlated with a lower relapse free survival and overall survival compared to patients without Cyclin D1 overexpression.Erb2 is overexpressed in 15-30% of breast cancers. In the Gruppo Universitario Napoletano 1 trial, ER+ patients with early stage node negative breast cancer who overexpressed ErbB2 had no improvement in progression free survival and overall survival with 2 years of adjuvant tamoxifen therapy. Additional retrospective studies have supported initial reports of an association between overexpression of ErbB2 and tamoxifen resistance.Methods: 69 patients who had the Oncotype DX assay performed and had unstained pathology slides available were assessed for ErbB2 and Cyclin D1 expression. ErbB2 overexpression status was also obtained in another 74 patients who had the Oncotype DX assay performed. ErbB2 overexpression was determined from a review of medical records where ErbB2 was defined as being positive if immunohistochemical (IHC) staining intensity was 3+ with >90% of cells expressing ErbB2 or FISH revealed an amplification of >2.0. IHC analysis of Cyclin D1 was performed according to standard protocol and using commercially available antibodies. Scoring of slides for Cyclin D1 staining were performed by blinded pathologists who assessed both extent and intensity of nuclear staining for Cyclin D1.Results: The median Oncotype Dx RS within ErbB2+ patients was significantly higher than ErbB2- patients (36.5 vs. 18 p<0.0001), and approximately 50% of patients within each RS grouping (high, intermediate, and low) overexpressed cyclin D1.Conclusion: ErbB2 overexpression among high RS patients suggests the Oncotype DX assay may predict tamoxifen resistance and other markers for tamoxifen resistance need to be correlated with the RS. Although preliminary analysis of the IHC staining for Cyclin D1 does not correlate with a high RS, high Cyclin D1 expression among patients within the low RS subgroup is concerning since this subgroup may have an increased likelihood of disease relapse when treated with adjuvant tamoxifen alone. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3035.

HOXB13 protein expression predicts the benefit of tamoxifen treatment in breast cancer patients.

Abstract Abstract #6038 Background: The two-gene expression ratio HOXB13:IL17BR, originally from a microarray analysis, has been shown to be indicative of clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer, with a high ratio associated with decreased disease-free survival. Analysis of a cohort of breast cancer patients randomized to 2 or 5 years of adjuvant tamoxifen therapy showed that the two-gene ratio and expression of the HOXB13 gene alone were predictive of the benefit of prolonged tamoxifen treatment. Patients with tumors expressing HOXB13 at high levels were unresponsive to prolonged adjuvant treatment, suggesting that this gene is involved in tamoxifen resistance. It is suggested that a high two-gene ratio may indicate impaired ER signaling, which is known to predict resistance to tamoxifen. To our knowledge, there are no studies investigating the HOXB13 protein levels in breast cancer.
 Methods: We have analyzed the protein expression of HOXB13 with immunohistochemistry in tumor samples from 912 postmenopausal node negative breast cancer patients randomized to 2 years of tamoxifen or no endocrine treatment. After 2 years, recurrence-free patients were randomized to 3 more years of tamoxifen, or no further therapy. This selection enabled us to investigate the treatment predictive value of HOXB13.
 Results: Data on HOXB13 protein expression were obtained from 866 patients (see table). Tamoxifen treated patients with estrogen receptor (ER) positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (hazard ratio (HR) 0.37, 95% CI 0.23-0.60, p=0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the distant recurrence-free survival compared to the untreated patients (HR=0.83, 95% CI 0.45-1.54, p=0.55). The interaction between HOXB13 expression and benefit from tamoxifen was statistically significant (p=0.046). HOXB13 did not have any prognostic value among systemically untreated patients.
 
 Conclusions: HOXB13 protein level may be used as a predictive marker for tamoxifen treatment, but does not have any prognostic value. Patients with a high expression of HOXB13 do not seem to benefit from tamoxifen. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6038.

A case of prolonged disease-free survival in a patient with choroidal metastasis from breast cancer

A 57-year-old woman presented with distorted vision and decreased visual acuity (finger count only) in her left eye, 6 years after she had undergone a lumpectomy, lymph-node dissection, and radiation therapy for a 1.1 cm infiltrating ductal carcinoma of her right breast. A year before this presentation, she had completed 5 years of adjuvant tamoxifen therapy. Physical examination, including a thorough ophthalmologic evaluation; laboratory investigations, ocular fluorescein angiography, ocular ultrasonography, head CT, chest X-ray, abdominal ultrasonography, bone scan, and bilateral mammography. Choroidal metastasis from breast carcinoma, with no other evidence of disease recurrence. Radiation therapy to the left eye followed by ongoing hormonal therapy with oral letrozole 2.5 mg daily for the past 9.5 years.

Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

Continuing with letrozole offers greater benefits

Tamoxifen has been at the foundation of adjuvant treatment to prevent disease recurrence in postmenopausal women with hormone-responsive early breast cancer. After 5 years of adjuvant tamoxifen therapy, however, options for further treatment are limited. Additional tamoxifen is not indicated, as no further benefit in disease-free survival (DFS) has been observed. The aromatase inhibitor letrozole significantly improves DFS over placebo in postmenopausal women who have completed 4.5-6.0 years of adjuvant tamoxifen. This article reviews the data supporting extended adjuvant letrozole therapy. Extended adjuvant letrozole has been shown to be particularly effective in patients with node-positive disease, who are at a higher risk for disease recurrence, improving both DFS and overall survival. Extended adjuvant letrozole is associated with a significant increase in self-reported osteoporosis, but no significant increases in fracture, endometrial malignancies, hypercholesterolemia, or cardiovascular events and no worsening of quality of life, making it suitable for long-term use. The ASCO treatment guidelines recommend at least 2.5 years of extended adjuvant letrozole for patients completing tamoxifen therapy, based upon the MA.17 trial follow-up period. A recent cohort analysis now suggests that extended adjuvant letrozole treatment for at least 48 months is associated with greater benefit. The efficacy of letrozole for up to 10 years following tamoxifen is also being investigated.

Extended adjuvant therapy with letrozole: reducing the risk of recurrence

Patients with all stages of primary breast cancer are at continuing risk of relapse following 5 years of adjuvant tamoxifen therapy, even in the absence of lymph node involvement. Tamoxifen has been the standard therapy for reducing risk of recurrence, although more than 50% of relapses and deaths occur after completion of tamoxifen. Tamoxifen use is associated with an increased risk of serious side effects, and extended use beyond 5 years may have a negative impact on disease-free survival. Extended adjuvant letrozole therapy confers a significant benefit in relapse-free survival. The approval of letrozole for this indication in the USA and in many European countries introduces a new, safe and effective treatment for disease-free patients seeking to reduce their long-term risk of recurrence.

Tratamiento anti-hormonal adyuvante en mujeres post-menopáusicas con diagnóstico de carcinoma de mama

Over the recent decades, tamoxifen has been considered the standard adjuvant treatment of postme-nopausal women with hormone-receptor positive breast cancer based on its capacity to reduce the annual breast cancer death. More recently, several major randomized controlled trials carried out with three different new aromatase inhibitors used either from the time of primary surgery or after 2-3 or 5 years of adjuvant tamoxifen therapy have shown a significant improvement in disease-free survival with respect to tamoxifen therapy. The described treatment-related side effects suggest different profiles of toxicity. Musculoskeletal disorders and cardiovascular events are the most serious side effects associated with the use of aromatase inhibitors, as well as the thromboembolic events and endometrial abnormalities are associated with tamoxifen therapy. An optimal treatment strategy for aromatase inhibitors administration, interventions to prevent or alleviate treatment-related side effects and identification of women at higher risk having more benefit with aromatase inhibitors need to be addressed.

Comparison of adverse effects on lipid metabolism of Anastrozole with tamoxifen in adjuvant setting for postmenopausal women with early breast cancer

Tamoxifen has been the endocrine treatment of choice for all stages of oestrogen receptor positive breast cancer for 20 years and the first chemical therapeutic to be tested to reduce the incidence of breast cancer in high-risk women. It is now clear that the oestrogen receptor is proving to be an invaluable target for the treatment and chemoprevention of breast cancer. The success of tamoxifen clinically can be quantitated: 400 000 women are alive today because of the application of 5 years of adjuvant tamoxifen therapy in node-positive and node-negative breast cancer. This advance has resulted in vigorous efforts to reduce side-effects and to improve objective response rates by the rapid application of laboratory principles. Tamoxifen is known to have a mixture of oestrogen-like and anti-oestrogen actions so it is reasoned that completely anti-oestrogenic agents would enhance treatment response rates while lowering the incidence of oestrogen-like side-effects such as endometrial cancer and blood clots. A new pure anti-oestrogen, fulvestrant, that destroys the oestrogen receptor, is available after drug resistance to tamoxifen develops. The group of drugs known as aromatase inhibitors block the production of oestrogens from androstenedione and testosterone in the body fat of postmenopausal women. New agents such as anastrozole, exemestane, and letrozole have shown promise as new treatment modalities for advanced breast cancer. Most importantly, the successful testing of anastrozole as an adjuvant treatment for breast cancer has enhanced enthusiasm for the evaluation of aromatase inhibitors and selective oestrogen receptor modulators (SERMs) to be tested as chemopreventives. SERMs express anti-oestrogenic actions in the breast but oestrogen-like actions in bone and lower circulating cholesterol. This insight not only allowed the safe application of tamoxifen to well high-risk women to test the worth of an ‘anti-oestrogen’ to prevent breast cancer, but also caused a paradigm shift in the strategy of chemoprevention. The question was posed that if, tamoxifen prevents breast cancer but an added benefit is the maintenance of bone density, why not develop a drug to prevent osteoporosis or atherosclerosis that prevents breast cancer in the general population as a beneficial side-effect? Raloxifene is the result of this new strategy to seek multifunctional medicines for women's health. Raloxifene is currently available for the treatment and prevention of osteoporosis but is being tested in high-risk postmenopausal women for the prevention of breast cancer against tamoxifen in the study of tamoxifen and raloxifene (STAR trial) and for the prevention of coronary heart disease (CHD) in a placebo-controlled trial in women at high risk for CHD called raloxifene use for the heart (RUTH).

Coronary Heart Disease Mortality After 5 Years of Adjuvant Tamoxifen Therapy: Results from a Randomized Trial

From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94; P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed.

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer

Background: Five years of tamoxifen therapy hasbeen the standard of care for the adjuvant treatment of estrogen receptor-positive early-stage breast cancer for many years and was the first hormonal treatment for postmenopausal women with advanced or metastatic disease. The third-generation aromatase inhibitors (AIs) anastrozole, exemestane, and letrozole offer new treatment options, although their efficacy has not been compared directly in randomized, double-blind, controlled trials in any breast cancer treatment setting. Objective: The goal of this article was to review theresults of recent randomized, controlled clinical trials of the AIs in the settings of neoadjuvant, adjuvant, and advance d/metastatic breast cancer. Methods: MEDLINE was searched for descriptions of randomized, controlled clinical trials published from 1990 to 2005 using the terms breast cancer, aromatase, aromatase inhibitor, anastrozole, exemestane, and letrozole. Abstracts from the proceedings of several oncology meetings held between 2001 and 2005 were searched to capture relevant emerging data. Results: In 2 Phase III trials comparing an AI withtamoxifen for the adjuvant treatment of breast cancer in postmenopausal women, disease-free survival was significantly improved with anastrozole and letrozole compared with tamoxifen as initial adjuvant treatment ( P = 0.01 and P = 0.003, respectively). A switch to either anastrozole (2 Phase III trials) or exemestane (1 Phase III trial) after 2 to 3 years of adjuvant tamoxifen therapy was more effective in reducing the risk of recurrence than continued tamoxifen therapy ( P = 0.006, P < 0.002, and P < 0.001, respectively); data on switching to letrozole are expected soon. In another Phase III trial, letrozole was found to improve disease-free survival in the extended adjuvant setting ( P :≤ 0.001) and was the only AI consistently more effective than tamoxifen in the neoadjuvant setting. In 3 Phase III studies (1 letrozole vs tamoxifen, 2 anastrozole vs tamoxifen), both anastrozole and letrozole were more efficacious than tamoxifen in the first-line setting, and some patients receiving letrozole had better overall response rates compared with those receiving anastrozole in the second-line setting (19.1% vs 12.3%, respectively; P = 0.013). In a patient-preference study, those receiving letrozole reported fewer adverse events than those receiving anastrozole (43% vs 65%; P < 0.003), and more patients preferred letrozole to anastrozole (68% vs 32%; P < 0.01). Conclusions: Currently, anastrozole and letrozoleare associated with the most complete data over the breast cancer care continuum, with efficacy in early-stage, locally advanced, and metastatic disease. In-direct comparisons suggest stronger evidence for the use of letrozole compared with other AIs for breast cancer in postmenopausal women who require estrogen-deprivation therapy. Data from randomized, double-blind comparative studies will help clarify the differences between AIs.

The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L)

The purpose of this study was to evaluate changes in serum lipid parameters {cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein(a) [Lp(a)]}, in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer (NCIC CTG MA.17L). MA.17L is a substudy of MA.17, a randomized, double-blind, placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen. Patients consenting to participate in this companion study had blood drawn and lipid parameters (total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a), triglycerides) evaluated at baseline, 6 months, 12 months and yearly thereafter until completion of protocol therapy. It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial. Three hundred and forty seven women were enrolled in the study. The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months (P=0.049), in LDL cholesterol at 12 months (P=0.033) and triglycerides at 24 months (P=0.036). All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups. No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups. The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen. Results from this study suggests that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or Lp(a) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy. These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following standard tamoxifen therapy.

Oestrogens, Oestrogen Receptors and Breast Cancer

Tamoxifen has been the endocrine treatment of choice for all stages of oestrogen receptor positive breast cancer for 20 years and the first chemical therapeutic to be tested to reduce the incidence of breast cancer in high-risk women. It is now clear that the oestrogen receptor is proving to be an invaluable target for the treatment and chemoprevention of breast cancer. The success of tamoxifen clinically can be quantitated: 400 000 women are alive today because of the application of 5 years of adjuvant tamoxifen therapy in node-positive and node-negative breast cancer. This advance has resulted in vigorous efforts to reduce side-effects and to improve objective response rates by the rapid application of laboratory principles. Tamoxifen is known to have a mixture of oestrogen-like and anti-oestrogen actions so it is reasoned that completely anti-oestrogenic agents would enhance treatment response rates while lowering the incidence of oestrogen-like side-effects such as endometrial cancer and blood clots. A new pure anti-oestrogen, fulvestrant, that destroys the oestrogen receptor, is available after drug resistance to tamoxifen develops. The group of drugs known as aromatase inhibitors block the production of oestrogens from androstenedione and testosterone in the body fat of postmenopausal women. New agents such as anastrozole, exemestane, and letrozole have shown promise as new treatment modalities for advanced breast cancer. Most importantly, the successful testing of anastrozole as an adjuvant treatment for breast cancer has enhanced enthusiasm for the evaluation of aromatase inhibitors and selective oestrogen receptor modulators (SERMs) to be tested as chemopreventives. SERMs express anti-oestrogenic actions in the breast but oestrogen-like actions in bone and lower circulating cholesterol. This insight not only allowed the safe application of tamoxifen to well high-risk women to test the worth of an ‘anti-oestrogen’ to prevent breast cancer, but also caused a paradigm shift in the strategy of chemoprevention. The question was posed that if, tamoxifen prevents breast cancer but an added benefit is the maintenance of bone density, why not develop a drug to prevent osteoporosis or atherosclerosis that prevents breast cancer in the general population as a beneficial side-effect? Raloxifene is the result of this new strategy to seek multifunctional medicines for women's health. Raloxifene is currently available for the treatment and prevention of osteoporosis but is being tested in high-risk postmenopausal women for the prevention of breast cancer against tamoxifen in the study of tamoxifen and raloxifene (STAR trial) and for the prevention of coronary heart disease (CHD) in a placebo-controlled trial in women at high risk for CHD called raloxifene use for the heart (RUTH).

Tamoxifen: toxicities and drug resistance during the treatment and prevention of breast cancer.

Tamoxifen, a nonsteroidal antiestrogen, is the endocrine therapy of choice for all stages of breast cancer. There are six million women-years of experience with tamoxifen, and the drug has produced survival advantages in node-positive and node-negative patients who have had 2-5 years of adjuvant tamoxifen therapy. A low incidence of side effects has been reported with tamoxifen, resulting in the proposal to use the antiestrogen as a preventive agent for breast cancer. Three separate clinical trials are currently under way--in the United States, Italy, and the United Kingdom. Current concerns about tamoxifen are the development of rat liver tumors during long-term treatment and an increased incidence of endometrial carcinomas observed in patients. Another concern is the development of drug resistance to long-term tamoxifen therapy. There is increased interest in both determining the mechanism of drug resistance and evaluating new antiestrogens that may be more beneficial as a preventive, as an adjuvant therapy, or for the treatment of advanced breast cancer.

Intestinal and pelvic endometriosis presenting as a tumor and associated with tamoxifen therapy: Report of a case

Tamoxifen has been used in the adjuvant treatment of breast cancer because of its antiestrogenic effects. However, recent reports have shown it to have estrogenic effects as well. The purpose of this report is to describe a potential association between tamoxifen therapy and endometriosis.A 50-year-old postmenopausal woman who had received 2 years of adjuvant tamoxifen therapy for breast carcinoma developed extensive tumor-like endometriosis necessitating extensive pelvic and intestinal surgery.This case report highlights the need for obstetricians and gynecologists to be familiar with the actions of tamoxifen and its potential complications.

Intestinal and pelvic endometriosis presenting as a tumor and associated with tamoxifen therapy: Report of a case

Tamoxifen has been used in the adjuvant treatment of breast cancer because of its antiestrogenic effects. However, recent reports have shown it to have estrogenic effects as well. The purpose of this report is to describe a potential association between tamoxifen therapy and endometriosis. A 50-year-old postmenopausal woman who had received 2 years of adjuvant tamoxifen therapy for breast carcinoma developed extensive tumor-like endometriosis necessitating extensive pelvic and intestinal surgery. This case report highlights the need for obstetricians and gynecologists to be familiar with the actions of tamoxifen and its potential complications.

Intestinal and pelvic endometriosis presenting as a tumor and associated with tamoxifen therapy: Report of a case

Background: Tamoxifen has been used in the adjuvant treatment of breast cancer because of its antiestrogenic effects. However, recent reports have shown it to have estrogenic effects as well. The purpose of this report is to describe a potential association between tamoxifen therapy and endometriosis. Case: A 50-year-old postmenopausal woman who had received 2 years of adjuvant tamoxifen therapy for breast carcinoma developed extensive tumor-like endometriosis necessitating extensive pelvic and intestinal surgery. Conclusion: This case report highlights the need for obstetricians and gynecologists to be familiar with the actions of tamoxifen and its potential complications.(Obstet Gynecol 1993;82:642-4)