Emerging data on optimal adjuvant endocrine therapy: Breast International Group trial 1-98/MA.17

In recent years, several major trials have studied aromatase inhibitors (AIs)/inactivators as adjuvant therapy for postmenopausal women with early-stage breast cancer. The AIs have demonstrated improved efficacy compared with 5 years of tamoxifen when used as initial therapy or when used sequentially after 2-3 years. They also improve outcomes when used after 5 years of adjuvant tamoxifen in this patient population. In all cases, AIs improve disease-free survival compared with the standard 5 years of adjuvant tamoxifen, leading to a reassessment of the optimal adjuvant endocrine therapy for postmenopausal patients with breast cancer. The American Society of Clinical Oncology now recommends the inclusion of an AI into the adjuvant regimen at some point for most postmenopausal patients with hormone receptor-positive early-stage breast cancer. However, the optimal duration of AI therapy and the comparative efficacy and safety of the alternative strategies for their incorporation remain matters of debate. In addition, the long-term impact of AIs on other organs, such as the bone and cardiovascular systems, is not completely understood, and longer follow-up of patients from these original trials as well as carefully planned future trials with appropriate substudies are essential to determine the optimal endocrine treatment strategy.     

Aromatase inhibitors in postmenopausal breast cancer patients

Aromatase inhibitors (AIs) have greatly enriched the treatment of hormone receptor-positive breast cancer in postmenopausal patients. Before the introduction of the well-tolerated third-generation AIs, tamoxifen was the mainstay of endocrine therapy for hormone receptor-positive breast cancer. Many clinical trials have shown the superiority of AIs compared with tamoxifen in adjuvant breast cancer treatment, as well as their benefit in metastatic breast cancer. NCCN guidelines recommendations for their use are based on the evidence provided by these clinical trials. This discussion reviews the evidence supporting the current guidelines for use of AI therapy in the treatment of hormone receptor-positive postmenopausal breast cancer patients.     

Recent perspectives of endocrine therapy for breast cancer

The choice of endocrine therapy for breast cancer depends on the menopausal status and stage of disease. Endocrine therapy remains the first choice and most important component in the treatment of hormone sensitive non-life threatening advanced breast cancer. In premenopausal women with metastatic disease, the combination of a luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen is reasonable as first-line endocrine therapy. In postmenopausal patients with recurrent disease progressing after or during adjuvant tamoxifen, third-generation aromatase inhibitors (AIs) are the preferred first-line endocrine treatment. Many premenopausal and postmenopausal women with hormone responsive breast cancer benefit from sequential use of endocrine therapies at the time of disease progression. Recent clinical trials designs have been implemented, employing AIs as monotherapy in postmenopausal breast cancer patients, as first-line adjuvant therapy, and in sequence either 2-3 or 5 years, with initial tamoxifen. Emerging results from these trials indicate an advantage to patients for any of these strategies, and most international guidelines now suggest the use of an AI in the adjuvant setting in postmenopausal women. The use of endocrine treatment for metastatic and early breast cancer will be reviewed here.     

Breast cancer adjuvant endocrine therapy

Adjuvant endocrine therapy with the selective estrogen receptor modulator, tamoxifen, has significantly improved mortality from early-stage breast cancer for both pre- and postmenopausal women with hormone receptor-positive breast cancer. Recent large clinical trials have demonstrated a clear and consistent benefit for the incorporation of aromatase inhibitor (AI) therapy within adjuvant endocrine regimens for postmenopausal women. The AIs, which are associated with myalgias, arthralgias, and a reduction in bone mineral density, are generally well tolerated and have lower risks of endometrial carcinoma and thromboembolic events than tamoxifen. Data are awaited from ongoing trials to better define the optimal sequencing strategy, duration, and AI agent. Attempts to further optimize adjuvant endocrine therapy by identifying predictive biomarkers of response, as well as by developing strategies to overcome endocrine resistance are underway. In premenopausal women AI monotherapy is currently contraindicated and tamoxifen remains the standard of care. The role of ovarian function suppression in addition to tamoxifen or combined with AI therapy is being explored. The hope is that continued advances in endocrine therapy will translate into improved survival among both pre- and postmenopausal women with receptor-positive breast cancer.     

Aromatase inhibitor plus ovarian suppression as adjuvant therapy in premenopausal women with breast cancer

The goal of adjuvant hormonal therapy for breast cancer is to prevent recurrence by eradicating micrometastatic disease. Recent studies have shown that the use of aromatase inhibitors (AIs) as adjuvant therapy improves outcomes for postmenopausal women with estrogen receptor (ER)-positive breast cancer compared to adjuvant endocrine therapy with tamoxifen alone. The research question has been raised whether AIs would have similar improvements in disease-free survival (DFS) in premenopausal women with ER-positive breast cancer. Combining 2 phase 3 clinical trials (n = 4,690), Pagani and colleagues randomized premenopausal women with ER-positive early breast cancer to exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 y. After a median follow-up of 68 months, DFS was 91.1% in the AI group and 87.3% in the tamoxifen group. In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence.     

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations

Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor-positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node-positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor-positive breast cancer.     

First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen?

Until recently, endocrine therapy for breast cancer was relatively simple. If the tumour expressed hormone receptors, regardless of stage and age, tamoxifen was indicated. While this largely remains the case for premenopausal women, clinical trials in postmenopausal women have broadened our choice to include one of three selective aromatase inhibitors (AIs), the nonsteroidal agents anastrozole or letrozole and the steroidal agent exemestane. Comparative data concerning the efficacy, toxicity, tolerability and cost of AI vs tamoxifen continues to evolve with over 40 000 women slated to be involved in clinical trials. Currently, tamoxifen remains an appropriate choice for adjuvant treatment, and will remain so unless a clear survival advantage emerges for adjuvant AI therapy. However, anastrozole is widely seen as a useful alternative, with particular merit for patients prone to the development of serious tamoxifen side effects. For endocrine therapy na?ve advanced disease, several trials have provided evidence that a nonsteroidal AI has replaced tamoxifen as optimal treatment. In the neoadjuvant setting, letrozole was also more effective than tamoxifen, both in terms of response rates and the incidence of breast-conserving surgery, and so AI therefore also dominates this evolving indication. The ongoing adjuvant clinical trials ask all the relevant questions regarding tamoxifen and AI in combination, sequence and duration, except for 5 years of an AI vs a longer period. For both the advanced and early-stage disease, resistance remains the key obstacle to overcome, and trials that combine endocrine agents with signal transduction inhibitors such as HER1 and HER2 kinase inhibitors, farnesyl transferase inhibitors, mTOR inhibitors as well as COX2 inhibitors are being developed in a concerted attempt to address this problem.     

The evolving role of aromatase inhibitors in adjuvant breast cancer therapy

The development of third-generation aromatase inhibitors (AIs) has brought about a major change in the therapeutic approach to patients with hormone-sensitive breast cancer. In randomized clinical trials, each of the third-generation AIs has demonstrated efficacy in the adjuvant treatment of postmenopausal women with receptor-positive tumors. Anastrozole has been shown to improve disease-free survival when compared with standard first-line tamoxifen, letrozole has been shown to further reduce the rate of breast cancer events when given as extended adjuvant therapy in women completing between 4.5 and 6 years of tamoxifen, and exemestane has been shown to improve disease-free survival when substituted for tamoxifen after an initial 2-3 years of adjuvant therapy. Although long-term follow-up for safety and overall survival continues in each of these trials, currently available data suggest that an AI should now be included as part of adjuvant endocrine therapy for the great majority of receptor-positive postmenopausal patients. To address these rapidly evolving issues related to the endocrine adjuvant treatment of postmenopausal women, an expert panel met in March 2004 in Hamburg, Germany, the site of the Fourth European Breast Cancer Conference. The panel's overview of recent endocrine data is presented along with updated results where available. In addition, case-based discussions are included to provide direction on how to integrate recent endocrine adjuvant clinical trial findings into everyday practice.     

Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer

For the past 25 years, the estrogen antagonist tamoxifen has been the hormonal treatment of choice for postmenopausal patients with hormone-sensitive metastatic and early breast cancer (EBC). However, tamoxifen is associated with certain tolerability and safety concerns. In addition, the hormonal options after progression are limited, and thus, alternative endocrine treatments have been developed. This review provides a synopsis of the newer alternatives in endocrine therapy of breast cancer: the aromatase inhibitors (AIs) and fulvestrant Faslodex), the estrogen receptor antagonist that downregulates estrogen and progesterone receptors and has no known agonist activity. The third-generation AIs, anastrozole and letrozole, have been shown to be as effective or more effective than megestrol acetate and tamoxifen as second- and first-line therapies for the treatment of postmenopausal patients with metastatic breast cancer, and exemestane has been approved for second-line use. Fulvestrant has been shown to be as effective as anastrozole as second-line therapy for metastatic breast cancer and has been approved in the U.S. for the treatment of postmenopausal women with hormone-receptor-positive metastatic breast cancer following progression on antiestrogen therapy. Anastrozole is the only AI with published clinical trial data and U.S. Food and Drug Administration approval for adjuvant therapy of postmenopausal women with EBC. The 'Arimidex,' Tamoxifen, Alone or in Combination (ATAC) trial, a double-blind, multicenter trial with 9,366 patients, compared tamoxifen with anastrozole, alone and in combination, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, EBC. The first analysis (at a median follow-up of 33.3 months) showed longer disease-free survival and, in general, better tolerability with anastrozole than with tamoxifen. This pattern was maintained at later analyses with a median follow-up of 47 months for efficacy and 37 months for safety and tolerability. Although longer follow-up is warranted, anastrozole appears to be a well-documented choice of endocrine adjuvant therapy for postmenopausal women with hormone-responsive breast cancer.     

The role of aromatase inhibitors in early breast cancer

Opinion statement The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptorpositive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.     

Defining the roles of aromatase inhibitors in the adjuvant treatment of early-stage breast cancer

The widespread use of tamoxifen has led to significant improvements in survival for postmenopausal women with early-stage hormone receptor-positive breast cancer; however, approximately 30% of patients die despite receiving tamoxifen as adjuvant treatment. In addition, concerns exist regarding tamoxifen-associated side effects, including endometrial cancer and thromboembolic disease. The development of the third-generation aromatase inhibitors (AIs; anastrozole, exemestane, and letrozole) therefore represented a welcome potential alternative to tamoxifen. Several clinical trials have demonstrated the superiority of AIs over tamoxifen in the adjuvant treatment of postmenopausal women with hormone-sensitive breast cancer, but these trials differ in their design and in the characteristics of their patient populations. This review discusses the different designs of the primary adjuvant, switching, extended adjuvant, and sequencing trials that are investigating the use of AIs in the adjuvant treatment of breast cancer and provides direction regarding how the data from these trials could be used to guide treatment choice. This review also demonstrates why one should not extrapolate results from clinical trials to clinical situations that differ from the clinical trial or from clinical trials investigating a particular AI to clinical situations involving another AI.     

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know?

Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)-positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)--including anastrozole, letrozole, and exemestane--are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5-6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2-3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.     

Safety considerations of adjuvant therapy in early breast cancer in postmenopausal women

Because of its proven efficacy profile based on long-term data, tamoxifen has been the standard adjuvant endocrine therapy for hormone-sensitive early breast cancer for the past 30 years. However, there is well-established evidence that long-term use of tamoxifen is associated with serious side effects. As adjuvant endocrine therapy is generally administered for long periods of time, the safety and tolerability of agents used in this setting are of particular importance. Due to their superior efficacy over tamoxifen, newer agents, such as the third-generation aromatase inhibitors (AIs), are already established therapies for the treatment of advanced breast cancer. In addition, recent trials indicate that the AI anastrozole ('Arimidex') has improved efficacy compared with tamoxifen in the adjuvant setting in postmenopausal women. The other third-generation AIs have reported disease-free survival benefits but not in the absence of prior treatment with tamoxifen; letrozole ('Femara') has been compared with placebo following 5 years of tamoxifen therapy and exemestane ('Aromasin') has been compared with tamoxifen following 2-3 years of prior treatment with tamoxifen. Long-term safety data show that anastrozole also has a more favorable overall safety profile compared with tamoxifen, particularly in terms of life-threatening events such as endometrial cancer and thromboembolism. Anastrozole alone, therefore, provides a new option for adjuvant therapy in postmenopausal women with hormone-receptor-positive early breast cancer. The AIs have differing pharmacological profiles, which may translate into dissimilar adverse event profiles in the adjuvant treatment setting, but patient follow-up in most trials is relatively short to make a valid comparison. It cannot, therefore, be assumed that all AIs will be equally well tolerated in the adjuvant setting. Further data on the long-term safety of AIs other than anastrozole are therefore required to allow overall risk:benefit assessments on these agents to be made.     

A comparison of the efficacy of aromatase inhibitors in second-line treatment of metastatic breast cancer

Randomized clinical trials have established the role of third-generation aromatase inhibitors (AIs) (letrozole, anastrozole, and exemestane) as standard treatment for patients with hormone-sensitive metastatic breast cancer who have experienced disease progression with antiestrogen therapy. Significant gains in clinical efficacy and improved tolerability over progestins (megestrol acetate) and the first-generation AI aminoglutethimide have positioned these agents above previous therapies. Estrogen receptor (ER) status remains the best predictive determinant of endocrine response, and further randomized trials with properly selected patient populations may distinguish individual AIs within this class. A recently completed, randomized, head-to-head phase III trial of letrozole versus anastrozole as second-line endocrine therapy demonstrated a significant difference in objective response rate for letrozole compared with anastrozole (19% versus 12%, respectively; P = 0.014), with similar time to progression. The improved efficacy and safety of AIs as second-line endocrine therapies has spawned trials of their use as first-line endocrine therapy versus tamoxifen for patients with metastatic breast cancer. Based on favorable results from these trials, letrozole and anastrozole have also been approved for use as first-line treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer.     

A woman's heart

Adjuvant therapy in postmenopausal women with breast cancer may contribute to the expression of underlying cardiovascular disease or expose the heart to additional toxicities. Tamoxifen remains an important component of endocrine therapy for breast cancer, although major clinical trials of the aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane suggest that these agents are more effective and better tolerated alternatives to tamoxifen. The AIs inhibit the conversion of androgens to estrogen in postmenopausal women; consequently, their mechanism of action differs from that of tamoxifen. Accordingly, although it has been observed that tamoxifen has some favorable effects on cardiovascular risk, such as reducing total cholesterol levels, because of its partial estrogen‐agonist properties, no such effects exist for the AIs. Some studies, particularly those that compare the AIs with tamoxifen, have suggested a less favorable impact of adjuvant AI therapy on cardiovascular risk. Comorbid conditions, including cardiovascular disease, emerge as competing causes of death as women with breast cancer continue to live longer, and the potential impact of adjuvant therapies on cardiovascular risk becomes an increasingly important consideration for clinicians. Cancer 2009. © 2009 American Cancer Society.     

The latest is the greatest? Results of a structured lecture about aromatase inhibitor use for breast cancer

Summary Background The aromatase inhibitors (AIs) are increasingly surpassing tamoxifen as the endocrine treatment of choice for postmenopausal breast cancer patients. With their increasing use, there is concern that they are being inadvertently prescribed to pre- and peri-menopausal women. Methods As part of a continuing medical education program for 264 practicing surgeons, a 15-min lecture was given over viewing hormone therapy for early stage breast cancer. Two multi-choice questions were asked before and after the lecture regarding the optimal hormonal treatment for pre and postmenopausal women. Results For the optimal treatment of premenopausal women, 36% of respondents chose tamoxifen before the lecture, rising to 82% after it (p<0.01). However 37% suggested an AI would be best, with a further 27% choosing either an AI or tamoxifen, falling to 7% and 11% respectively after the lecture. Before the lecture, 30% of the participants stated that any of the listed treatment options; tamoxifen alone, an AI alone or a combination of tamoxifen and an AI would be acceptable for postmenopausal women. Following the lecture, 53% chose this option (p<0.01). Conclusions In many countries it is practicing surgeons who commence endocrine therapy for patients with breast cancer. The findings of this study are useful from two points. Firstly it is clear that many physicians feel that AIs are an effective adjuvant endocrine therapy for premenopausal breast cancer. Secondly it demonstrates the benefits of continuing medical education as a significant improvement in test scores was noted after a structured lecture.     

Adjuvant endocrine therapy for breast cancer

Endocrine therapy is a critical part of adjuvant therapy in women with hormone receptor-positive breast cancer, and has been shown to reduce the risk of recurrence and death from breast cancer. For decades, 5 years of tamoxifen has been the standard treatment. For premenopausal women, it remains so, and we await the results of ongoing trials to define the role of ovarian suppression or ablation with endocrine therapy. If a woman becomes postmenopausal during treatment, consideration should be given to extended adjuvant therapy with an aromatase inhibitor (AI) for another 5 years. In postmenopausal women, trials have shown that AIs are more beneficial than tamoxifen in preventing disease recurrence.They have been compared as upfront treatment for 5 years, as sequential therapy after 2 to 3 years of tamoxifen, and as extended treatment for 5 years after 5 years of tamoxifen. Among the questions still being studied are the optimal duration of extended adjuvant therapy with AIs, how one AI performs compared to another, and whether there is a benefit to intermittent extended adjuvant treatment.     

Adjuvant endocrine therapy for early breast cancer

Breast cancer is the most common cancer among women and about 80% of breast cancers express hormone receptors. Tamoxifen has been the most important form of adjuvant endocrine therapy over the last 25 years. The third generation aromatase inhibitors (AIs) are a new class of drugs challenging the central role of tamoxifen as adjuvant endocrine treatment in postmenopausal women with hormone receptor-positive breast cancer. Their effectiveness has been demonstrated in first line therapy as well in neoadjuvant setting with a statistically significant superiority over tamoxifen. Here we considered the role of adjuvant AIs in early stage breast cancer with an analysis reviewing the main adjuvant trials. We considered efficacy, side effects, optimal timing, duration of the therapy and whether specific subgroups may achieve particular benefit. In conclusion the upfront use of adjuvant anastrozole or letrozole is superior to tamoxifen with a good relative toxicity profile. Tamoxifen will continue to have a role where recurrence risk is low or if AI is poorly tolerated. Issues including the timing of administration (up-front or sequential), the duration of the therapy and the role of biomarkers such as PgR and HER2 in optimal selection remain unresolved.     

Shifting paradigms in hormonal therapy for breast cancer

BACKGROUND: Tamoxifen has been the mainstay of endocrine treatment for postmenopausal patients with early and advanced breast cancer for many years. However, as an anti-estrogen with partial estrogenic effects, tamoxifen also has some serious safety and tolerability issues. Following tamoxifen treatment failure there were initially limited options for subsequent therapy. Therefore, new agents, including new anti-estrogens and aromatase inhibitors (AIs) were developed. METHODS: Data for this review were identified by searches of PubMed and references from relevant articles. Abstracts were included only when the relevant information had not been published in full elsewhere. Only papers published in English were included. RESULTS: The AIs have been shown to be effective treatments for hormone-sensitive metastatic breast cancer. CONCLUSIONS: Current clinical trial data in early breast cancer show longer disease-free survival and time to recurrence with anastrozole than that demonstrated with tamoxifen and very good general tolerability, although longer follow-up is warranted. Clinical trials of the use of AIs in breast cancer prevention and preliminary data for the combination of anastrozole with a gonadotrophin-releasing hormone for the treatment of premenopausal women with early stage breast cancer are also discussed here.     

Optimizing endocrine therapy for premenopausal and postmenopausal women with breast cancer

The majority of invasive breast cancer patients present with hormone receptor-positive disease, and modulation of estrogen receptor (ER) activation is an essential component of systemic adjuvant therapy for these women. While tamoxifen has traditionally been the primary adjuvant endocrine therapy for all ER-positive women, recent trials evaluating the use of aromatase inhibitors (AIs) have challenged this standard in postmenopausal women, and ongoing trials are examining the optimal use of endocrine therapy in younger women. Issues regarding the optimal approach to endocrine therapy in both pre- and postmenopausal women are examined in this review.