The ATAC trial: the vanguard trial for use of aromatase inhibitors in early breast cancer

The Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial was the first trial to explore the use of aromatase inhibitors in post-menopausal women with early breast cancer and is the largest published cancer treatment trial in breast cancer. The main results have been published at 33-, 47- and 68-month median follow-up, and further analyses are planned for the end of 2007 and in 2010. This trial demonstrated that 5 years of treatment with anastrozole was generally better tolerated than 5 years of treatment with tamoxifen, and led to lower recurrence rates, especially in receptor-positive women (26% reduction). The side-effect profile was different than that for tamoxifen, with fewer hot flushes, gynecologic symptoms, endometrial cancers, strokes and thromboembolic events; however, an increased incidence of fractures, joint symptoms and carpal tunnel syndrome was observed. Future analyses will determine whether benefits and fracture rates persist after stopping treatment, and the extent to which currently marginal benefits on late end points, such as distant recurrence and death after recurrence, are sustained or improved.     

Review of the ATAC study: tamoxifen versus anastrozole in early-stage breast cancer

A 5-year regimen of tamoxifen hormone therapy has historically been the recommendation for hormone receptor-positive, postmenopausal women with early-stage breast cancer. With the advent of aromatase inhibitors, there has been extensive work carried out to investigate the role of these agents in the adjuvant setting. Studies have been designed to answer whether these agents should be used upfront (instead of tamoxifen) or in conjunction (either in a switch or extended program). The Arimidex^®, Tamoxifen Alone or in Combination (ATAC) trial is a landmark trial that demonstrated the superiority of upfront anastrozole over tamoxifen. This article reviews the trial and discusses both the optimum timing of initiation of aromatase inhibitors and the future approach of more individualized therapy, with the detection of predictive markers.     

Cost-effectiveness analysis of anastrozole vs tamoxifen in adjuvant therapy for early stage breast cancer in the United Kingdom: the 5-year completed treatment analysis of the ATAC ('Arimidex', Tamoxifen alone or in combination) trial

Results from the completed treatment analysis of the ATAC (Arimidex, Tamoxifen alone or in combination) trial indicated that anastrozole was significantly superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal women with hormone receptor-positive (HR+) early breast cancer. On the basis of these results, this study estimated the cost-effectiveness of anastrozole vs tamoxifen, from the perspective of the UK National Health Service (NHS). A Markov model was developed using the 5-year completed treatment analysis from the ATAC trial (ISRCTN18233230), as well as data obtained from published literature and expert opinion. Resource utilisation data and associated costs (2003-4 UK pound) were compiled from standard sources and expert opinion. Utility scores for a number of health states were obtained from a cross-sectional study of 26 representative patients using the standard gamble technique. The utility scores were then inserted into the model to obtain cost per quality adjusted life-year (QALY) gained. Costs and benefits were discounted at recommended annual rates of the UK Treasury (3.5%). Modelled for 25 years, anastrozole, relative to generic tamoxifen, was estimated to result in 0.244 QALYs gained per patient at an additional cost of pound4315 per patient). The estimated incremental cost-effectiveness of anastrozole compared with tamoxifen was pound17 656 per QALY gained. There was a greater than 90% probability that the cost-effectiveness of anastrozole was below pound30 000 per QALY gained and of the order of 65% that it was below pound20 000 per QALY gained. The results were robust to all parameters tested in sensitivity analysis. Compared with commonly accepted thresholds, anastrozole is a cost-effective alternative to generic tamoxifen in adjuvant treatment of postmenopausal women with HR+ early breast cancer from the UK NHS perspective.     

The scientific value of preoperative studies and how they can be used

Preoperative hormonal therapy appears to be an effective option for the treatment of breast cancer and this treatment approach enables breast conservation surgery to be performed instead of mastectomy in patients with large, operable tumors. Short-term preoperative trials are valuable for research of established agents where differential efficacy in biologically distinct subgroups is to be investigated. They can be used to generate hypotheses that can be further examined in suitably powered clinical trials. Longer-term ‘thera-peutic trials’, in which surgery is delayed over a period of months, not only allow for a reduction in tumor size with treatment, but also provide an opportunity to perform a detailed analysis of biomarker expression. Recent advances in hormonal preoperative studies and the increasing importance of prognostic and predictive factors in the management of patients with breast cancer are discussed in this review. Indeed, several clinical studies have been performed in the preoperative setting and it is now apparent that the aromatase inhibitors, such as letrozole (‘Femara’) and anastrozole (‘Arimidex’), are valid new treatment options at this stage of treatment. This revised version was published online in August 2006 with corrections to the Cover Date.     

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

Background:

This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT).

Methods:

From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients.

Results:

One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response.

Conclusions:

We could not support the ‘normalization hypothesis'' and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed.     

Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial.

BACKGROUND: Estrogen has beneficial effects on lipid metabolism and bone preservation. The IMPACT trial evaluated neoadjuvant therapy with anastrozole or tamoxifen alone, or a combination. The comparative effects of these treatments on serum lipids and bone resorption were assessed. PATIENTS AND METHODS: Non-fasting clotted blood samples were taken from 176 postmenopausal patients at baseline, 2 and 12 weeks for assessment of serum levels of estradiol, the bone resorption marker CTx and lipid profiles [total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and non-HDL cholesterol (N-HDL-C)]. RESULTS: After 12 weeks, tamoxifen was associated with a significant increase in HDL-C (26.5%), and a decrease in TC (6.5%) and N-HDL-C (12.3%). Anastrozole was associated with a significant increase in HDL-C (11.2%), and a non-significant increase in TC (2.9%) and N-HDL-C (3.4%), both of which were significantly different from tamoxifen. The combination was associated with a significant increase in HDL-C (9.4%), and a decrease in TC (10.9%) and N-HDL-C (13.9%). For tamoxifen and the combination, there were non-significant decreases in CTx compared with a significant increase (45.6%) with anastrozole. No correlation between serum estradiol and CTx was seen in any of the treatment groups. CONCLUSION: Anastrozole did not have a detrimental effect on lipid profiles following 3 months of therapy. There was a significant increase in CTx with anastrozole in contrast to tamoxifen.     

The Breast International Group 1-98 trial: big results for women with hormone-sensitive early breast cancer

As there is a risk for relapse in early breast cancer, especially at 1–3 years post surgery, the need for adjuvant therapy is clear. In terms of disease-free survival, aromatase inhibitors have emerged as superior to tamoxifen for the adjuvant treatment of hormone-sensitive breast cancer in several Phase III clinical trials. Of these trials, the Breast International Group (BIG) 1-98 trial stands out as unique in design, as it is the only trial to address whether an aromatase inhibitor is more effective as initial adjuvant therapy or as sequential therapy with an aromatase inhibitor and tamoxifen in either order and in rigor of end points and safety evaluations. When compared with tamoxifen, letrozole has been shown to significantly reduce recurrence risk in the overall population by 19% and also significantly reduced recurrence risk in the patient subgroups at increased risk: node-positive and previously chemotherapy-treated patients. Letrozole is the only aromatase inhibitor to demonstrate a significant 27% reduction in the risk of distant metastases (p = 0.001) in the clinically relevant, hormone receptor-positive population in the initial adjuvant setting. Recent results also suggest that letrozole in particular reduces the risk of distant metastases early on after initial surgery for breast cancer. This is important, as early distant metastatic events compose the majority of early recurrences and are a well-recognized predictor of breast cancer death. Letrozole has been found to be well tolerated in the initial adjuvant treatment setting, and these data have been confirmed by long-term safety data from the monotherapy analysis in the BIG 1-98 study. Thus far, the results from the BIG 1-98 trial provide clear support for the use of letrozole in the initial adjuvant treatment of breast cancer. Future studies will provide the definitive answer to questions of which initial adjuvant therapy is superior (i.e., anastrozole or letrozole) and information as to the optimal treatment strategy (i.e., initial adjuvant aromatase inhibitor therapy or sequential adjuvant aromatase inhibitor therapy).     

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data

Tamoxifen is the established adjuvant treatment for postmenopausal women with hormone-sensitive early breast cancer. However, the side-effects associated with tamoxifen therapy have prompted a search for safer and potentially more effective endocrine agents. Results from randomized trials of the third-generation aromatase inhibitors, anastrozole, letrozole and exemestane, demonstrating improved efficacy compared with tamoxifen and favorable tolerability profiles, are discussed in this review.     

Canadian initiatives for locally advanced breast cancer research and treatment: inaugural meeting of the Canadian Consortium for LABC

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference.     

Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients. Participants and Methods: Post‐menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5–6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression‐based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1–T2 difference scores that would be expected on the basis of practice and error alone. Results: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected. Conclusion: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area. Copyright © 2008 John Wiley & Sons, Ltd.     

Refining the postmenopausal breast cancer treatment paradigm: the FACE trial

It is clear that letrozole and anastrozole provide significant benefits for patients with breast cancer. However, possible differences in efficacy have been suggested by varying degrees of aromatase inhibition and effectiveness in the neoadjuvant and first-line settings. Analyses of aromatase inhibitor-treated patient subgroups within the Arimidex, Tamoxifen, Alone or in Combination trial and Breast International Group 1–98 trial, and the National Cancer Institute of Canada Clinical Trials Group’s MA.17 study, have also suggested some differences in efficacy. The question is how best to maximize these differences to benefit specific patient subgroups, such as postmenopausal women with node-positive disease. Nodal status is one of the strongest prognostic factors for breast cancer recurrence and several studies have shown that patients with node-positive disease are at higher risk for early relapse. It is thought that patients at increased risk for early relapse may be better treated with an aromatase inhibitor upfront, but the guidelines are unclear as to which aromatase inhibitor should be used. To answer this important question quickly, the Femara Anastrozole Clinical Evaluation (FACE) trial is recruiting node-positive patients and randomizing them to receive either early adjuvant letrozole or early adjuvant anastrozole. The trial has been designed to differentiate between the two drugs in the shortest possible time frame by using patients at increased risk of early recurrence of breast cancer, so that the required number of events to initiate analysis will be obtained more quickly. In total, 4000 patients who have recently undergone surgery for node-positive primary breast cancer (and who have no clinical or radiological evidence of recurrent disease or metastasis) are being enrolled around the world. The FACE trial will not only provide an efficacy evaluation between these two aromatase inhibitors but also provide a valuable head-to-head comparison of the safety profiles of adjuvant letrozole and anastrozole. The data will be transferred to an independent academic organization, the Istituto Nazionale Tumori (Michelangelo Foundation, Milan, Italy), which will verify and analyze the data, removing any perception of bias. An Independent Data Monitoring Committee will then decide when and how the trial data are to be released. The results are expected to further refine the treatment paradigm for breast cancer in postmenopausal patients with node-positive disease.     

Endocrine therapy for male breast cancer: rates of toxicity and adherence

Purpose

Most male breast cancer tumours are hormone receptor–positive; the patients therefore receive endocrine therapy. There is, however, a paucity of published data on toxicities experienced by male breast cancer patients who are prescribed endocrine therapy. In the present study, we examined rates of adherence to and toxicity from endocrine treatments in male breast cancer patients treated at a single institution.

Patients and Methods

We conducted a retrospective study of male patients diagnosed with breast cancer at The Ottawa Hospital Cancer Centre during 1981–2003. Data collected included patient age, hormone receptor status, therapy adherence, self-reported toxicities, and type and duration of endocrine therapies.

Results

The review located 59 cases of early-stage and metastatic male breast cancer. Median patient age was 68.0 years. Tamoxifen was given to 38 patients (64.4%), anastrozole to 8 (13.6%), and letrozole to 5 (8.5%). Of patients who received endocrine therapy, 10 (25%) received adjuvant systemic chemotherapy. Toxicity was reported by 19 patients taking tamoxifen (50%), with hot flashes being the most common complaint (18.4%). Decreased libido, weight gain, and malaise were reported by 5 patients (13.2%). Rash and erectile dysfunction were reported by 3 patients (7.9%). Increased liver enzymes, pulmonary embolism, superficial thrombophlebitis, myalgia, depression, visual blurring, and loose stools were each reported in 1 patient (2.6%). Tamoxifen therapy was discontinued secondary to toxicity in 9 patients (23.7%). Of the patients treated with anastrozole, 3 (37.5%) reported toxicity, with 1 report each of decreased libido, leg swelling, and depression (12.5%). Toxicity was reported in 2 patients taking letrozole (40%), with both reporting peripheral edema, and 1 reporting hot flashes. No patient discontinued anastrozole or letrozole because of toxicity.

Conclusions

Few studies specifically report data on adherence to and toxicities from endocrine therapies in male breast cancer patients. The rate of discontinuation at our institution because of toxicity (23.7%) is similar to that reported in the female breast cancer population. Future prospective studies should explore strategies to improve adherence to endocrine therapy in this population.     

The ATAC trial: the vanguard trial for use of aromatase inhibitors in early breast cancer

The Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial was the first trial to explore the use of aromatase inhibitors in post-menopausal women with early breast cancer and is the largest published cancer treatment trial in breast cancer. The main results have been published at 33-, 47- and 68-month median follow-up, and further analyses are planned for the end of 2007 and in 2010. This trial demonstrated that 5 years of treatment with anastrozole was generally better tolerated than 5 years of treatment with tamoxifen, and led to lower recurrence rates, especially in receptor-positive women (26% reduction). The side-effect profile was different than that for tamoxifen, with fewer hot flushes, gynecologic symptoms, endometrial cancers, strokes and thromboembolic events; however, an increased incidence of fractures, joint symptoms and carpal tunnel syndrome was observed. Future analyses will determine whether benefits and fracture rates persist after stopping treatment, and the extent to which currently marginal benefits on late end points, such as distant recurrence and death after recurrence, are sustained or improved.     

Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial

BackgroundThis ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial sub-study examined the effects of anastrozole and tamoxifen on bone mineral density (BMD) following 5 years of treatment.Patients and methodsLumbar spine and total hip BMD were assessed at years 6 and 7 in a total of 71 eligible patients. In total, 50 patients had evaluable data.ResultsFollowing anastrozole treatment, the lumbar spine median BMD increased by 2.35% (P = 0.04) and 4.02% (P = 0.0004) at years 6 and 7, while total hip median BMD increased by 0.71% (P = 0.3) and 0.5% (P = 0.8). After tamoxifen treatment, lumbar spine median BMD decreased by 0.79% (P = 0.2) and 0.30% (P = 0.9) at years 6 and 7, while total hip median BMD decreased by 2.09% (P = 0.0003) and 2.52% (P = 0.0002). Patients with a normal BMD or who were osteopenic at 5 years did not become osteoporotic.ConclusionsAnastrozole treatment-related bone loss did not continue into the off-treatment follow-up period. The recovery in lumbar spine BMD and absence of further loss at the hip is consistent with the reduction in the annual rate of fracture observed after treatment cessation in the main ATAC trial.     

Three years' follow-up from the ATAC trial is sufficient to change clinical practice: a debate

Tamoxifen is currently the adjuvant treatment of choice for postmenopausal women with hormone-sensitive breast cancer. However, in the treatment of postmenopausal women with advanced disease, the third-generation aromatase inhibitor anastrozole ('Arimidex') has been shown to be at least as effective as tamoxifen, and to be more effective than tamoxifen in patients with estrogen receptor-positive disease. Furthermore, anastrozole is well tolerated and is associated with fewer adverse reactions (such as thromboembolic events, vaginal bleeding, and endometrial cancer) compared with tamoxifen. A change in clinical practice has now emerged for the first-line treatment of postmenopausal advanced disease in patients, with tamoxifen becoming the second- or third-line choice for many clinicians. These data have raised questions about the optimal adjuvant treatment for postmenopausal women with early breast cancer. The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial has compared the efficacy and safety of tamoxifen and anastrozole in the adjuvant treatment of postmenopausal women with early breast cancer. At 3 years' follow-up in the overall population, anastrozole demonstrated a significant benefit compared with tamoxifen for disease-free survival (DFS) (89.4% vs. 87.4%; p = 0.013), time to recurrence (hazard ratio = 0.79; p = 0.008), and contralateral breast cancers (odds ratio = 0.42; 95% confidence interval: 0.22-0.79; p = 0.007). Anastrozole produced improvements in quality of life similar to tamoxifen and was better tolerated for a number of predefined adverse events. Of course, a large body of evidence is available regarding the safety profile of tamoxifen and some feel that more data are needed from the ATAC trial to demonstrate that the early advantages of anastrozole over tamoxifen can be maintained in the longer term. However, a follow-up analysis at 47 months has confirmed that the tolerability profile and the absolute benefit of anastrozole were maintained over the extended follow-up period, demonstrating that the benefits of anastrozole are likely to be maintained over the long term. This review assesses these and other data from the ATAC trial and presents the arguments for and against whether 3 years' follow-up is sufficient to inform a change in clinical practice for the adjuvant treatment of postmenopausal women with early breast cancer.     

Fulvestrant (Faslodex™): current status in the therapy of breast cancer

Fulvestrant (Faslodex?, formerly ICI 182,780) is a potent steroidal antiestrogen that mediates its effects by estrogen receptor downregulation. It appears to act as a pure anti-estrogen and exhibits none of the negative side effects associated with the partial agonist activity of tamoxifen. It has been shown to be as effective as the oral aromatase inhibitor anastrozole in postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy, principally tamoxifen. It therefore provides the clinician with an alternative therapeutic strategy following the development of tamoxifen resistance. Fulvestrant might also have potential as a follow-on therapy after tamoxifen in an adjuvant setting and help alleviate some of the concerns surrounding long-term (up to 5 years) tamoxifen therapy.     

Multicancer early detection test: Preclinical,translational, and clinical evidence–generation plan and provocative questions

Minimally invasive molecular biomarkers have been applied to the early detection of multiple cancers in large scale case-control and cohort studies. These demonstrations of feasibility herald the potential for permanent transformation of current cancer screening paradigms. This commentary discusses the major opportunities and challenges facing the preclinical development and clinical validation of multicancer early detection test strategies. From a diverse set of early detection research perspectives, the authors recommend specific approaches and highlight important questions for future investigation.     

Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial

The ATAC trial evaluates in a randomized, double-blind design, Arimidextrade mark (anastrozole) alone or in combination with tamoxifen, relative to tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for > or =3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 +/- 4 h after last dose. Trough (C(min)) plasma concentrations of anastrozole, tamoxifen and desmethyltamoxifen (DMT) were measured by validated methods. The PK results were based on a total of 347 patients (131 anastrozole (1 mg o.d.), 111 tamoxifen (20 mg o.d.), 105 anastrozole and tamoxifen (1 and 20 mg o.d. respectively)). The geometric mean steady-state trough plasma concentrations of tamoxifen and DMT were statistically equivalent in patients receiving tamoxifen alone or in combination with anastrozole: geometric mean tamoxifen = 94.8 ng ml(-1)and 95.3 ng ml(-1)in tamoxifen alone and combination groups, respectively; geometric mean DMT = 265.1 and 277.6 ng ml(-1)in the tamoxifen and anastrozole and tamoxifen groups, respectively. The geometric mean anastrozole levels were 27% lower (90% Cl 20-33%;P< 0.001) in the presence of tamoxifen than with anastrozole alone. Baseline plasma oestradiol levels were not obtained in the PK sub-protocol, however, such information was available from a similar ATAC sub-protocol, which evaluated bone mineral density. Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l(-1)prior to treatment and 3.7, 20.9 and 3.6 pmol l(-1)after 3 months in the anastrozole, tamoxifen, and combination groups, respectively (n = 167). On-treatment values were below the detection limit (3 pmol l(-1)) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by tamoxifen is unlikely to be of clinical significance when anastrozole and tamoxifen are administered together.     

Anastrozole as adjuvant therapy for early-stage breast cancer: implications of the ATAC trial

Tamoxifen has been the gold standard adjuvant therapeutic agent for postmenopausal women with hormone-sensitive breast cancer for > 25 years. Although it continues to play an important role in treating premenopausal women, tamoxifen's association with some serious safety and tolerability issues, including increased incidence of endometrial cancer and thromboembolic events, may be cause to limit its use in postmenopausal women. Anastrozole was the first drug to show improved efficacy and safety compared with standard therapies for first- and second-line therapy of hormone-sensitive advanced breast cancer in postmenopausal women. This article provides a review of the results of the first major analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) early-stage breast cancer trial, initiated in 1996, and discusses the implications for the use of anastrozole in the adjuvant setting. This randomized, double-blind, multicenter trial compared tamoxifen (20 mg once daily) with anastrozole (1 mg) alone and in combination with tamoxifen, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, early-stage breast cancer. The results of the ATAC trial show anastrozole to be more effective and better tolerated than tamoxifen in this group of patients, and an updated follow-up suggests the therapeutic index for anastrozole will continue to remain superior to that of tamoxifen. Anastrozole is now emerging as a new standard for the adjuvant treatment of postmenopausal women with hormone-sensitive early-stage breast cancer. New adjuvant trials are currently using anastrozole in the control arm.     

A Review of the Efficacy of Anastrozole in Postmenopausal Women with Advanced Breast Cancer with Visceral Metastases

Tumors that have spread to the liver or lungs (visceral metastases) are associated with a worse prognosis than tumors in soft tissue and bone only. Here we review available efficacy data to address whether or not anastrozole, a non-steroidal aromatase inhibitor (AI), is effective in postmenopausal patients with advanced breast cancer (ABC) and visceral metastases. We include data from Phase III clinical trials, comparing clinical benefit (CB) with anastrozole versus tamoxifen as a first-line treatment, and versus megestrol acetate (MA) or fulvestrant as a second-line therapy. Patients in these trials had adequate organ function and the volume of disease had to be minimal or moderate for them to be eligible for inclusion. First-line treatment of patients with or without visceral metastases in the overall population resulted in CB rates of 49.5 and 62.3%, respectively, for anastrozole and 46.9 and 55.9%, respectively, for tamoxifen. In patients with confirmed hormone receptor (HR)-positive tumors, the CB rate was 51.9 and 65.7%, respectively, for anastrozole and 41.6 and 58.7%, respectively, for tamoxifen. In patients with or without visceral metastases, second-line treatment with anastrozole resulted in a CB rate of 31.4 and 51.8%, respectively, compared with 31.9 and 47.1%, respectively, for those treated with MA. Patients in the overall population with and without visceral metastases treated with anastrozole obtained a CB rate of 37.4 and 43.8%, respectively, while those treated with fulvestrant obtained a CB rate of 38.2 and 47.6%, respectively. In patients with confirmed HR-positive tumors, CB was seen in 37.6 and 41.5%, respectively, of patients treated with anastrozole and in 37.3 and 47.0%, respectively, of patients treated with fulvestrant. The results reveal anastrozole to be an effective and valuable first- and second-line therapy in postmenopausal women with ABC and visceral metastases, showing similar CB to other endocrine therapies.