Arimidex, Tamoxifen, Alone Or In Combination Research Articles

Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5.

PurposeEstimating risk of late distant recurrence (DR) is an important goal for managing women with hormone receptor–positive breast cancer after 5 years of endocrine treatment without recurrence. We developed and validated a simple clinicopathologic tool (Clinical Treatment Score post–5 years [CTS5]) to estimate residual risk of DR after 5 years of endocrine treatment.Patients and MethodsThe ATAC (Arimidex, Tamoxifen, Alone or in Combination) data set (N = 4,735) was used to create a prognostic score for post–5-year risk of DR. Validity of CTS5 (ATAC) was tested in the BIG 1-98 data set (N = 6,711). Time to late DR, 5 years after finishing scheduled endocrine therapy, was the primary end point. Cox regression models estimated the prognostic performance of CTS5 (ATAC).ResultsCTS5 (ATAC) was significantly prognostic for late DR in the ATAC cohort (hazard ratio, 2.47; 95% CI, 2.24 to 2.73; P < .001) and BIG 1-98 validation cohort (hazard ratio, 2.07; 95% CI, 1.88 to 2.28; P < .001). CTS5 (ATAC) risk stratification defined in the training cohort as low (< 5% DR risk, years 5 to 10), intermediate (5% to 10%), or high (> 10%) identified 43% of the validation cohort as low risk, with an observed DR rate of 3.6% (95% CI, 2.7% to 4.9%) during years 5 to 10. From years 5 to 10, 63% of node-negative patients were low risk, with a DR rate of 3.9% (95% CI, 2.9% to 5.3%), and 24% with one to three positive nodes were low risk, with a DR rate of 1.5% (95% CI, 0.5% to 3.8%). A final CTS5 for future use was derived from pooled data from ATAC and BIG 1-98.ConclusionCTS5 is a simple tool based on information that is readily available to all clinicians. CTS5 was validated as highly prognostic for late DR in the independent BIG 1-98 study. The final CTS5 algorithm identified 42% of women with < 1% per-year risk of DR who could be advised of the limited potential value of extended endocrine therapy.

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: misleading analysis and doubtful methodology.

Dear editor Zhao et al have presented the result of the relative cardiovascular safety profile in using anastrozole, letrozole, and exemestane to treat the postmenopausal estrogen receptor-positive breast cancer, in which fatal or nonfatal myocardial infarction is the outcome measure and ten randomized controlled trials are used as the data sources.1 We congratulate and applaud their important work, but there are some issues of concern. First, the difference in duration of adjuvant tamoxifen therapy among the studies led to heterogeneity and inconsistency. For instance, the duration of tamoxifen therapy was 2 years in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) trial, whereas it was 5 years in the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial. In fact, the duration of tamoxifen therapy is relevant to toxicity. The practice of “lumping” cotreatments together generally makes no sense in clinical practice.2 In addition, the author regarded the sequential therapy (tamoxifen for 2 years followed by anastrozole for 3 years) or the extended adjuvant therapy (tamoxifen for 5 years followed by anastrozole for 3 years) as the anastrozole group, which was misleading. In fact, the tamoxifen would have the “crossover” effect even after the completion of the 2-, 3-, or 5-year treatment period. Instead, the author should have considered comparing the safety prolife among the initial aromatase inhibitor therapy, sequential therapy, and extended therapy, which would be of a more meaningful clinical significance. Second, the authors failed to include three relevant randomized controlled trials in their meta-analysis, although they apparently met their inclusion criteria.3–5 Third, there was one important methodological issue in this review. The reporting of the inconsistency between the direct and indirect comparison is laudable in a network meta-analysis. However, this review did not describe the methodology of the inconsistency analysis in the “Statistical analysis” section. Finally, in Figure 3, it was described that both severe and total cardiovascular risk deviance information criterion values were <200, which means that the calculated results were convincible. We are interested in the source of this perspective. In addition, the methodology of model fit was not confirmed in the “Statistical analysis” section.

Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score.

We have previously shown that the PAM50-based risk of recurrence (ROR) score is significantly correlated with distant recurrence in both the translational research cohort within the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial (TransATAC) and Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG 8) randomized trials. Here, we focus on the ROR score for predicting distant recurrence after 5 years of follow-up in a combined analysis of these two randomized trials. Long-term follow-up data and tissue samples were obtained from 2,137 postmenopausal women with hormone receptor-positive early-stage breast cancer from the ABCSG 8 and TransATAC trials. We used Cox proportional hazard regression models to determine the prognostic value of ROR for distant recurrence beyond 5 years in the combined data set. A total of 2,137 women who did not have a recurrence 5 years after diagnosis were included in the combined analyses. The Clinical Treatment Score (CTS) was the strongest prognostic factor 5 years after diagnosis (univariable: likelihood ratio [LR] χ(2) = 94.12, bivariable: LR χ(2) = 61.43). The ROR score was significantly prognostic by itself in years 5 to 10. In the node-negative/human epidermal growth factor receptor 2-negative subgroup, more prognostic value for late distant recurrence was added by the ROR score compared with the CTS. The ROR score added clinically meaningful prognostic information to the CTS in all patients and all subgroups in the late follow-up period. These results suggest that the ROR score may be helpful for separating patients into risk groups who could be spared or potentially benefit from extended hormonal therapy beyond 5 years of treatment.

Breast cancer chemoprevention: little progress in practice?

Breast cancer chemoprevention: little progress in practice?

Genesis and Outcome of a Breast Cancer Trial to Develop the Aromatase Inhibitor Anastrozole

Featured Article: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, ATAC Trialists' Group. Lancet 2005;365:60–2.2 Aromatase inhibitors block the enzyme aromatase, which is responsible for conversion of the adrenal derived precursor, androstenedione, to estrogen in tissues such as fat, muscle, and in the breast in postmenopausal women. Estrogens drive the proliferation and metastasis of estrogen receptor positive breast cancer (about 70% of the total). In the mid 20th century bilateral adrenalectomy was used to reduce postmenopausal estrogens but this major operation was replaced by use of the adrenal steroid hormone synthesis inhibitor, aminoglutethimide, although corticosteroid replacement had to be used. Aromatase inhibitors were the real advance, and the introduction of a simple once per day pill in the 1990s (1) lead the way to evaluation of their value, first in advanced breast cancer against standard therapy of tamoxifen …

Influence of Comorbidities and Age on Risk of Death Without Recurrence: A Retrospective Analysis of the Arimidex, Tamoxifen Alone or in Combination Trial

The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole, tamoxifen, or the combination. We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received, breast cancer-related mortality, and competing causes of mortality. The current analyses were based on 10-year median follow-up data in the two monotherapy arms (anastrozole, n = 3,092; tamoxifen, n = 3,094) of the ATAC study. Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age ≥ 70 years. The cumulative incidence of breast cancer-related and non-breast cancer-related mortality was assessed according to age and comorbidities. One thousand six hundred sixty-two patients (27%) were age ≥ 70 years at study entry. Older women were more likely to undergo mastectomy (odds ratio [OR], 1.92; 95% CI, 1.71 to 2.16) and less likely to receive radiotherapy (OR, 0.49; 95% CI, 0.44 to 0.55) or chemotherapy (OR, 0.24; 95% CI, 0.18 to 0.29). Women age ≥ 70 years had an increased risk of recurrence compared with women age less than 70 years (hazard ratio [HR], 1.21; 95% CI, 1.08 to 1.37) and a substantially increased risk of death without recurrence (HR, 4.13; 95% CI, 3.53 to 4.83). The risk of death without recurrence increased with comorbidity score (10-year estimates of 8.4%, 20.0%, and 30.4% for Satariano score 0, 1, and 2+, respectively; P < .001). Age influences the risk of recurrence, and age and comorbidities significantly influence the risk of death without recurrence. Formal assessment of comorbidities should be incorporated into decisions regarding adjuvant therapies.

Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients

The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.

Clinical Research: Show Us the Data

Clinical Research: Show Us the Data

Designing adjuvant treatment based on biological measurements in the neoadjuvant setting.

For many years, one of the main aims of neoadjuvant therapy has been to identify short term endpoints that will predict for long-term outcome in adjuvant treatment. Th e advantages are obvious: in contrast to adjuvant trials, neoadjuvant trials require hundreds rather than thousands of patients, are very much less expensive to run and produce outcome data many years earlier. A key primary endpoint for neoadjuvant trials has been objective clinical response and this still remains the case [1]. Nevertheless, major studies have frequently shown that clinical response, including complete clinical remission, does not predict for long-term outcome. For example, in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial no diff erence in outcome was seen between patients who achieved clinical response versus those who did not [2]. Likewise, in the NSABP B-27 trial in which 2,411 patients were randomised to neoadjuvant adriamycin/cyclophospha mide (AC) versus the same treatment followed by sequential docetaxel, the complete response rate was 64% for the sequential, docetaxel-containing arm compared with 40% for the AC arm alone (P < 0.001), but no signifi cant diff erence was seen in long-term survival [3,4]. Likewise, for neoadjuvant endocrine therapy, the IMPACT (Immediate Preopera tive Anastrozole, Tamoxifen, or Combined With Tamoxifen) trial compared neo adjuvant anastrazole versus tamoxifen versus the combination and was the neoadjuvant equivalent of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant trial. No signifi cant diff erence was seen in response rate between the three arms of IMPACT [5] and this failed, therefore, to correlate with the long-term disease-free survival advantage of anastrazole in ATAC. Likewise, in the IMPACT trial a large diff erence was seen in response rates for patients with human epidermal growth factor receptor 2 (HER2)-positive tumours in favour of anastrazole (7 of 12 responders; 58%) compared with tamoxifen (2 of 9 responders; 22%) and yet no selective disease-free survival advantage for anastrazole over tamoxifen in patients with HER2-positive tumours was subsequently seen in ATAC [6]. A possible explana tion for this is that it is entirely possible that tumour growth rate may be slowed by neoadjuvant therapy (as measured, for example, by a reduction in proliferation factor Ki67) without a formal clinical response being achieved but with a consequent gain in relapse free survival. In the IMPACT trial, for example, only 37% of tumours achieved an objective clinical response rate to anastrazole whereas 75% had a signifi cant reduction in Ki67 [7].

FACE: the barefaced facts of AI potency

The use of third-generation aromatase inhibitors (AIs), such as anastrozole and letrozole, as initial adjuvant hormonal therapy in postmenopausal women (PMW) with hormone receptor-positive (HR+) breast cancer offers a significant benefit over tamoxifen for reducing recurrence risk. Clinical studies, including the Arimidex Tamoxifen Alone or in Combination (ATAC) and the Breast International Group (BIG) 1–98 trials, have proven that both anastrozole and letrozole are, respectively, superior to tamoxifen in improving disease-free survival. Although differing in design, objectives, and follow-up time, these trials offer some insight into the comparative clinical efficacy of these two nonsteroidal AIs. In particular, results from BIG 1–98 show that letrozole significantly reduces early distant metastatic (DM) events, which constitute the majority of early recurrence events. Subsequently, there is a beneficial overall survival effect emerging in the trial, whereas survival is unchanged with anastrozole after 100 months of follow-up in ATAC. Significant differences in the potency of these two drugs, vis-à-vis their degree of aromatase inhibition, have been observed in comparative trials and show that letrozole causes a more complete suppression of estrogen levels than does anastrozole. Whether this difference in potency is relevant to reductions in DM events during adjuvant therapy remains unclear. The Femara Anastrozole Clinical Evaluation trial is addressing this issue in a more unequivocal manner by comparing initial adjuvant treatment with anastrozole or letrozole in a population of breast cancer patients at high risk of recurrence: PMW with HR+ disease and axillary lymph node involvement.

Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer

Background:The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole.Methods:A Markov model was used to estimate cost per quality-adjusted life-year (QALY) gained with letrozole vs. anastrozole from the US healthcare system perspective. Cost effectiveness was examined separately in treatment-naïve patients and in patients already receiving letrozole. For the latter, cost effectiveness of continued letrozole vs. therapeutic substitution (TS) to generic anastrozole was evaluated separately in cohorts defined on years of endocrine therapy remaining. TS to generic anastrozole was assumed to result in an additional 5% of patients discontinuing endocrine therapy. Probabilities of distant recurrence and death were taken from reports of BIG 1-98, ATAC, the Early Breast Cancer Trialists’ Collaborative Group meta-analysis of tamoxifen, and other published sources. Carry-over effects of aromatase inhibitors were assumed to be proportional to treatment duration. Costs of aromatase inhibitors were assumed to decline by 75% with generic availability.Results:In treatment-naïve patients, total expected lifetime costs are $3916 greater with letrozole vs. anastrozole. However, initiation of treatment with letrozole results in a gain of 0.15 QALYs. Cost per QALY gained with letrozole vs. anastrozole is $25 846. In patients already receiving letrozole, the increase in total expected lifetime costs with continued letrozole vs. TS to anastrozole is between $4200 and $4500 in all cohorts. QALYs gained with letrozole range from 0.21 in those with 4 years of endocrine therapy remaining to 0.13 in those with 1 year of therapy remaining. Cost per QALY gained ranges from $20 276 to $34 356.Conclusion:For postmenopausal women with HR+ early-stage breast cancer, letrozole is more likely to be cost effective vs. anastrozole in treatment-naïve patients and in patients already receiving letrozole. Limitations of the study include a lack of direct evidence comparing letrozole and anastrozole and lack of data on rates of discontinuation due to therapeutic substitution with aromatase inhibitors.

Effect of Body Mass Index on Recurrences in Tamoxifen and Anastrozole Treated Women: An Exploratory Analysis From the ATAC Trial

Third-generation aromatase inhibitors have been widely used in postmenopausal women for the adjuvant treatment of hormone receptor-positive breast cancer. As aromatase inhibitors work by inhibiting the conversion of androgens to estrogens in adipose tissue, we hypothesized that anastrozole may be more effective in women with a high body mass index (BMI). The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized clinical trial in which postmenopausal women with early-stage breast cancer were randomly assigned to receive oral daily anastrozole (1 mg) alone, tamoxifen (20 mg) alone, or the combination in a double-blind fashion. Analyses were based on the 100-month median follow-up for women with hormone receptor-positive breast cancers (estrogen [ER] and/or progesterone [PgR] positive). Here, we investigate the impact of BMI on recurrence and the relative benefit of anastrozole versus tamoxifen according to baseline BMI. Results Overall, women with a high BMI (BMI > 35 kg/m(2)) at baseline had more recurrences than those women with a low BMI (BMI < 23 kg/m(2); adjusted hazard ratio [HR], 1.39; 95% CI, 1.06 to 1.82; P(heterogeneity) = .03) and significantly more distant recurrences (adjusted HR, 1.46; 95% CI, 1.07 to 1.61; P(heterogeneity) = .01). Overall, the relative benefit of anastrozole versus tamoxifen was nonsignificantly better in thin women compared to overweight women. These results confirm the poorer prognosis of obese women with early-stage breast cancer. Recurrence rates were lower for anastrozole than tamoxifen for all BMI quintiles. Our results suggest that the relative efficacy of anastrozole compared to tamoxifen is greater in thin postmenopausal women and higher doses or more complete inhibitors might be more effective in overweight women, but this requires independent confirmation.

Phase 3 Trials of Aromatase Inhibitors for Breast Cancer Prevention

The third-generation aromatase inhibitors (AIs), anastrozole, exemestane, and letrozole are potential agents for preventing estrogen receptor (ER)-positive breast cancer (BC) in high-risk postmenopausal women. No AI has yet been fully evaluated for prevention. Each AI is incorporated into the design of a phase 3 randomized BC prevention trial based on hypothesis-generating contralateral breast cancer (CLBC) data from a corresponding adjuvant trial. Arimidex, tamoxifen alone or in combination (ATAC) pitted anastrozole against tamoxifen for 5 years as "initial adjuvant" therapy, showing at 33.3 months fewer CLBCs with anastrozole versus tamoxifen (odds ratio [OR] 0.42 overall; OR 0.29 ER-positive BCs), offering the hypothesis on which IBIS-II (International Breast Cancer Intervention Study) is based. "High-risk" IBIS-II compares anastrozole to placebo for the primary prevention of BC in 6000 postmenopausal women. IES (Intergroup Exemestane Study) compared exemestane to tamoxifen following 2-3 years of adjuvant tamoxifen in 4742 postmenopausal women with ER-positive BCs. The benefit from "switching" to exemestane in reducing CLBCs (HR 0.44 at 30.6 months) underlies MAP.3 (Mammary Prevention 3), which compares exemestane to placebo for primary BC risk reduction in 4560 postmenopausal women. MA.17 showed reduced CLBC incidence (HR 0.57) at 2.4 years in postmenopausal women with receptor-positive tumors receiving "extended adjuvant" letrozole compared to placebo following 5 years of tamoxifen. The Study of Letrozole and Raloxifene (STELLAR), using as the control raloxifene, the new U.S. standard drug for BC prevention, would complete the trio of AI prevention trials, but STELLAR is currently on hold.

Predictors and Temporal Trends of Adjuvant Aromatase Inhibitor Use in Breast Cancer

After the first report of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, adjuvant aromatase inhibitor use increased rapidly among National Comprehensive Cancer Network member institutions. Increased aromatase inhibitor use was associated with older age, vascular disease, overexpression of human epidermal growth factor receptor 2 (HER2), or more advanced stage, and substantial variation was seen among institutions. This article examines adjuvant endocrine therapy in postmenopausal women after the first report of the trial, identifies temporal relationships in aromatase inhibitor use, and examines characteristics associated with choice of endocrine therapy among 4044 postmenopausal patients with hormone receptor-positive nonmetastatic breast cancer presenting from July 1997 to December 2004. Multivariable logistic regression analysis examined temporal associations and characteristics associated with aromatase inhibitor use. Time-trend analysis showed increased aromatase inhibitor and decreased tamoxifen use after release of ATAC results (P < .0001). In multivariable regression analysis, institution (P <. 0001), vascular disease (P <. 0001), age (P = .0002), stage (P = .0002), and HER2 status (P = .0009) independently predicted aromatase inhibitor use. Institutional rates of use ranged from 15% to 66%. Adjuvant aromatase inhibitor use increased after the first report of ATAC, with this increase associated with older age, vascular disease, overexpression of HER2, or more advanced stage. Substantial variation was seen among institutions.

Characteristics of carpal-tunnel syndrome in the ATAC trial.

Abstract Abstract #5085 Introduction: Carpal-tunnel syndrome (CTS) is a condition in which the median nerve is compressed leading to pain and muscle weakness in fingers and the hand. Oestrogen depletion has been shown to induce CTS, whereas the use of hormone replacement therapy is associated with a resolution of the symptom. Aromatase inhibitors lead to profound oestrogen suppression and therefore might induce CTS in postmenopausal women.&amp;#x2028; Methods: The Arimidex Tamoxifen Alone or in Combination (ATAC) trial randomised 9,366 postmenopausal women to anastrozole (1mg/day), tamoxifen (20mg/day) or the combination. Analyses were based on the 100 month median follow-up data in women in the two monotherapy arms who started their allocated treatment (anastrozole=3,092; tamoxifen=3,094). Here, we retrospectively investigate the influence of anastrozole on CTS, clinical outcomes, the relative importance of a range of risk factors for CTS, and examine whether they act differently in the presence of anastrozole treatment.&amp;#x2028; Results: During the entire active treatment period, 80 (2.6%) cases of CTS were reported in the anastrozole arm compared with 23 (0.7%) in the tamoxifen arm (OR=3.55 (2.22-5.65), P&amp;lt;0.001). In both treatment arms, the majority of CTS were reported as of mild or moderate severity. Most reports of CTS in the anastrozole arm occurred within 18 months of treatment initiation, but incidence remained elevated compared to the tamoxifen arm for the entire treatment period. Median time to resolution of CTS was 8.4 months and none of the women stopped treatment medication due to this adverse event. 13 women underwent carpal-tunnel release surgery (11 anastrozole (1 in 300) vs. 2 tamoxifen (1 in 1500)). Reports of CTS were significantly increased for women who used prior hormone replacement therapy (HRT) (2.3% vs. 1.3%, OR=1.72 (1.16-2.54), P=0.007) or prior chemotherapy (2.5% vs. 1.4%, OR=1.73 (1.14-2.62)). Furthermore, women who were aged 60 years or younger at entry were at greater risk of CTS compared with those aged 61 years or older (2.5% vs. 1.2%, OR=0.48 (0.30-0.76), P=0.002). Body mass index (BMI), hormone receptor status, smoking status, and prior radiotherapy were not found to be risk factors for the development of CTS. When analyses were restricted to only women receiving anastrozole, the same risk factors were identified.&amp;#x2028; Conclusions: Although the use of anastrozole is clearly associated with a greater incidence of CTS, it is rare and most cases were of mild severity and short duration and did not lead to treatment discontinuation or surgical intervention. Thus, while CTS can be quite debilitating for the few patients who have severe symptoms, this side effect has minimal impact on the overall risk-benefit ratio for the use of anastrozole in postmenopausal women. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5085.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case against.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case against.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for

Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis

Joint symptoms (eg, arthralgia and arthritis) are a well-known side-effect of aromatase inhibitors. Low oestrogen concentrations and postmenopausal status are associated with the development of these symptoms. Chemotherapy can also induce joint symptoms, but tamoxifen seems to have little effect on their incidence. The aim of this study was to assess the relative importance of different risk factors for treatment-emergent joint symptoms in patients assigned to anastrozole or tamoxifen as adjuvant treatment for postmenopausal breast cancer. The Arimidex Tamoxifen Alone or in Combination (ATAC) trial randomly assigned 9366 postmenopausal women to anastrozole (1 mg/day), to tamoxifen (20 mg/day), or to a combination of both. Our analyses were based on data from case reports of 5433 women who were randomly assigned to anastrozole or tamoxifen, who started with their allocated treatment, and who did not have joint symptoms at entry (anastrozole group: n=2698; tamoxifen group: n=2735). The analysis was restricted to the occurrence of joint symptoms at any time during active treatment or within 14 days of its discontinuation. Joint symptoms were defined as any report of arthralgia, arthrosis, arthritis, or joint disorder on a case-report form. Joint disorders were defined as reports of cervical spondylosis, osteoarthritis, and disc herniation. The date of occurrence was recorded, along with a severity score (ie, mild, moderate, or severe). Our analyses were done by use of logistic regression. The ATAC trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. 777 of 1914 women (40.6%) who used hormone replacement therapy (HRT) before trial entry developed joint symptoms compared with 1001 of 3519 women (28.4%) without previous HRT use (odds ratio [OR] 1.72 [95% CI 1.53-1.93]). Women with hormone-receptor-negative breast cancer developed significantly fewer joint symptoms compared with those with hormone-receptor-positive tumours (124 of 461 [26.9%] vs 1556 of 4548 [34.2%]; OR 0.71 [0.57-0.88]). Women for whom chemotherapy was part of their initial treatment developed significantly more joint symptoms than those who did not receive it (461 of 1219 women [37.8%] vs 1317 of 4214 women [31.3%]; OR 1.34 [1.17-1.53]). Obese women (body-mass index [BMI] >30 kg/m(2)) reported more joint symptoms than women with a BMI of 25-30 kg/m(2) or those with a BMI <25 kg/m(2) (504 of 1354 women [37.2%] vs 502 of 1926 women [31.3%; OR 1.01 (0.88-1.16)] vs 592 of 1908 women [31.0%; OR 1.32 (1.14-1.53)]) and women on anastrozole reported more joint symptoms compared with those on tamoxifen (949 of 2698 women [35.2%] vs 829 of 2735 women [30.3%]; OR 1.25 [1.11-1.40]). All significant risk factors from the univariate analysis were included in a multivariate analysis and remained significant with little change. In this trial, the major risk factors for developing joint symptoms were previous HRT, hormone-receptor positivity, previous chemotherapy, obesity, and treatment with anastrozole. Discussion of identified risk factors is appropriate when counselling women before initiation of adjuvant hormonal treatment.

Clinical Trial Presentations, Agency Guidelines, and Oncology Practice: Findings from the Arimidex, Tamoxifen, Alone or in Combination Trial

Purpose Our objective was to explore the potential influence of agency guidelines/technology assessments regarding anastrozole use in clinical practice in the United States and European Union, based on findings related to the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial. Patients and Methods We examined temporal relationships among ATAC-related oral data presentations, peer-reviewed publications, regulatory agency approvals and agency guidelines/technology assessments to the patient days' use of anastrozole in the United States and European Union. Results Anastrozole usage increased at a relatively constant rate following oral presentations of ATAC results at oncology congresses and did not appear to be strongly influenced by publications or agency guidelines/technology assessments, which appeared to lag rather than lead clinical usage. Conclusion The presentation of clinical trial data at large international congresses rapidly changed anastrozole use in clinical practice regardless of ongoing guideline recommendations. This observation raises the following question: Have clinicians adopted adjuvant anastrozole use prematurely? Or, is the level of evidence required by expert panels higher than that with which oncologists in clinical practice are comfortable?

Clinico-pathological features and pathological Complete Responses (pCR) to primary chemotherapy (PC)

Our objective was to explore the potential influence of agency guidelines/technology assessments regarding anastrozole use in clinical practice in the United States and European Union, based on findings related to the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial.We examined temporal relationships among ATAC-related oral data presentations, peer-reviewed publications, regulatory agency approvals and agency guidelines/technology assessments to the patient days' use of anastrozole in the United States and European Union.Anastrozole usage increased at a relatively constant rate following oral presentations of ATAC results at oncology congresses and did not appear to be strongly influenced by publications or agency guidelines/technology assessments, which appeared to lag rather than lead clinical usage.The presentation of clinical trial data at large international congresses rapidly changed anastrozole use in clinical practice regardless of ongoing guideline recommendations. This observation raises the following question: Have clinicians adopted adjuvant anastrozole use prematurely? Or, is the level of evidence required by expert panels higher than that with which oncologists in clinical practice are comfortable?