Improved Overall Survival in Postmenopausal Women With Early Breast Cancer After Anastrozole Initiated After Treatment With Tamoxifen Compared With Continued Tamoxifen: The ARNO 95 Study

Kaufmann, M.; Jonat, W.; Hilfrich, J.; Eidtmann, Holger; Gademann, G.; Zuna, I.; Minckwitz, Gϋnter von

doi:10.1200/jco.2006.08.8054

Cited by 242 publications

(151 citation statements)

References 13 publications

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“…However, for convenience, the detection of CTCs could be used as an alternative to bone marrow for the identification of occult breast cancer cells and for monitoring minimal residual disease. This is of particular interest in the light of the results of recent trials, indicating that sequential treatment during the disease-free period may improve OS in breast cancer (Coombes et al, 2007;Kaufmann et al, 2007). Conceivably, secondary adjuvant treatment could be administered in patients selected on the basis of persisting CTCs.…”

Section: Discussionmentioning

confidence: 99%

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

et al. 2009

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BACKGROUND: To compare detection rates and evaluate the clinical relevance of cytokeratin-19 (CK-19) mRNA-positive cells in the peripheral blood (circulating tumour cells, CTCs) and bone marrow (disseminated tumour cells; DTCs) of patients with early breast cancer. METHODS: Paired samples of peripheral blood and bone marrow were obtained from 165 patients with stage I -II breast cancer before the initiation of adjuvant chemotherapy. In 84 patients, paired blood and bone marrow samples were also available after chemotherapy. The detection of CK-19 mRNA-positive CTCs and DTCs was assessed by real-time PCR. RESULTS: CK-19 mRNA-positive CTCs and DTCs were detected in 55.2 and 57.6% of patients before chemotherapy, respectively. After chemotherapy, CTCs and DTCs were identified in 44 (52.4%) and 43 (51.2%) of the 84 patients, respectively. There was a 93.9% (McNemar; P ¼ 0.344) and 72.6% (McNemar; P ¼ 0.999) concordance between blood and bone marrow samples before and after chemotherapy, respectively. The detection of CK-19 mRNA-positive CTCs or DTCs before chemotherapy was associated with decreased overall survival (P ¼ 0.024 and P ¼ 0.015, respectively). In addition, their simultaneous detection was also associated with an increased incidence of disease-related death and decreased overall survival (P ¼ 0.016). CONCLUSIONS: The detection of CK-19 mRNA-positive CTCs using reverse transcription-PCR (RT -PCR) both before and after chemotherapy is correlated with the detection of CK-19 mRNA-positive DTCs in patients with early-stage breast cancer. The determination of the CTC status by RT -PCR conveys clinically relevant information that is not inferior to DTC status and, owing to the ease of sampling, warrants further evaluation as a tool for monitoring minimal residual disease.

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Section: Discussionmentioning

confidence: 99%

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

et al. 2009

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“…One of the primary unresolved considerations is whether these drugs should be used instead of tamoxifen as initial adjuvant treatment for postmenopausal women with successfully resected EBC, or whether 2-3 years of tamoxifen should precede the implementation of AI therapy. The latter strategy, using either exemestane [Intergroup Exemestane Study (IES)] or anastrozole (Arimidex Nolvadex [ARNO] 95 study and others) as endocrine therapy following 2-3 years of tamoxifen, potentially offers treatment cost savings relative to upfront AIs and significant improvements in DFS, event-free survival (EFS), and overall survival (OS) relative to tamoxifen alone [5][6][7]11]. A significant caveat of the switching approach is that it effectively ''misses'' a sizable number of women who may relapse during the initial treatment period with tamoxifen; these patients have been excluded from AI switching trials such as the IES and ARNO 95 [5,11].…”

Section: Introductionmentioning

confidence: 99%

“…The latter strategy, using either exemestane [Intergroup Exemestane Study (IES)] or anastrozole (Arimidex Nolvadex [ARNO] 95 study and others) as endocrine therapy following 2-3 years of tamoxifen, potentially offers treatment cost savings relative to upfront AIs and significant improvements in DFS, event-free survival (EFS), and overall survival (OS) relative to tamoxifen alone [5][6][7]11]. A significant caveat of the switching approach is that it effectively ''misses'' a sizable number of women who may relapse during the initial treatment period with tamoxifen; these patients have been excluded from AI switching trials such as the IES and ARNO 95 [5,11]. Interestingly, in the Austrian Breast and Colorectal Study Group trial 8, the only reported sequencing trial that randomized patients at the time of surgery, the inclusion of recurrences during the tamoxifen period effectively negated the significant EFS benefit that was observed when these patients were not considered (hazard ratio [HR], 0.63; P = 0.010 compared with HR, 0.76; P = 0.068) [12].…”

Section: Introductionmentioning

confidence: 99%

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Mansell

Monypenny

Skene

et al. 2008

Breast Cancer Res Treat

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Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER?) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER? EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum).The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

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“…This may reflect the fact that AIs do not display the well-known protective effect of tamoxifen, although no evidence is present of any increase as compared with placebo (Jakesz et al 2005, Kaufmann et al 2007, Forbes et al 2008, Bliss et al 2012, Dubsky et al 2012, Boccardo et al 2013.…”

Section: Cardiovascular Adverse Eventsmentioning

confidence: 94%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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Improved Overall Survival in Postmenopausal Women With Early Breast Cancer After Anastrozole Initiated After Treatment With Tamoxifen Compared With Continued Tamoxifen: The ARNO 95 Study

Abstract: Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen.

Cited by 242 publications

References 13 publications

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

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