American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors as Adjuvant Therapy for Women With Hormone Receptor–Positive Breast Cancer: Status Report 2002

Winer, Eric P.; Hudis, Clifford A.; Burstein, Harold J.; Chlebowski, Rowan T.; Ingle, James N.; Edge, Stephen B.; Mamounas, Eleftherios P.; Gralow, Julie R.; Goldstein, Lori J.; Pritchard, Kathleen I.; Braun, Susan; Cobleigh, Melody A.; Langer, Amy S.; Perotti, Judy; Powles, Trevor J.; Whelan, Timothy J.; Browman, George P.

doi:10.1200/jco.2002.06.020

Cited by 217 publications

(109 citation statements)

References 36 publications

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“…16 Tumor proliferation in human mammary carcinoma was also significantly altered by androgens. 13 The results of adjuvant treatment of breast cancer with aromatase inhibitors, which block the conversion of adrenal steroids (mainly androgens) into estrogens, have been reported 17 and underscore the important role of androgens in the stimulation of human mammary carcinoma growth. Furthermore, studies on the effects of androgens and antiandrogens on breast carcinomas in long-term tissue cultures indicated that some human breast carcinomas, at least in vitro, Androgen receptors and mammary and extramammary Paget's disease B Liegl et al may be stimulated by androgens.…”

Section: Discussionmentioning

confidence: 99%

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease

2005

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Section: Discussionmentioning

confidence: 99%

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease

2005

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“…Endocrine therapies are the most effective systemic treatment of estrogen receptor a (ERa)-positive breast cancer, and over two-thirds of patients are considered to present with this kind of disease (EBCTCG, 1998;Chlebowski et al, 2002;Winer et al, 2002). Two major strategies mediate the efficacy of these therapies.…”

Section: Introductionmentioning

confidence: 99%

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

et al. 2010

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Endocrine therapies targeting the proliferative effect of 17b-estradiol through estrogen receptor a (ERa) are the most effective systemic treatment of ERa-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through molecular mechanisms that are not yet fully understood. The longterm estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERa. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were predicted to be influenced by transcription factors known to be involved in acquired resistance or cell proliferation (for example, interferon regulatory transcription factor 1 and E2F1, respectively) but, notably, not by canonical ERa transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)-to pS167-ERa were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERa-negative status, early response to letrozole and tamoxifen, and recurrence after tamoxifen treatment. In accordance with these profiles, MCF7-LTED cells showed increased sensitivity to inhibition of FGFR-mediated signaling with PD173074. This study provides mechanistic insight into acquired resistance to endocrine therapies of breast cancer and highlights a potential therapeutic strategy.

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“…Patient accrual was substantially limited by the introduction of aromatase inhibitors (12), which are now routinely used in patients discontinuing tamoxifen therapy at our medical center.…”

Section: Resultsmentioning

confidence: 99%

Prevention of Bone Loss After Withdrawal of Tamoxifen

et al. 2008

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Objective-To assess whether postmenopausal women with breast cancer have a rapid decline in bone mineral density (BMD) after completion of tamoxifen therapy, similar to that seen after estrogen withdrawal.Methods-We initiated a randomized, double-blind, placebo-controlled trial of alendronate (70 mg weekly) in an effort to prevent bone loss associated with discontinuation of tamoxifen therapy. Postmenopausal women with breast cancer were randomly assigned to receive alendronate or placebo for 1 year within 3 months after withdrawal of tamoxifen therapy. Patients treated with aromatase inhibitors were excluded from the study. BMD at the spine, hip, and forearm was measured at baseline and at 12 months. Repeated-measures analysis of variance was used for assessment.Results-Patient accrual was considerably limited by the substantial increase in use of aromatase inhibitors during the enrollment period. The study patients (N = 11) had similar baseline BMD Tscores in the alendronate (n = 6) and placebo (n = 5) subgroups. After 1 year, tamoxifen withdrawal was associated with a significant decline in BMD at the femoral neck, which appeared to be prevented by weekly administration of alendronate (−5.2% versus 0.1%; P = .02). Levels of urinary N-telopeptide, a marker of bone turnover, increased by 48% in study subjects in the placebo group (P < .01), whereas weekly alendronate treatment was associated with a 52% decline (P < .01) in this bone resorption marker.Conclusion-Differences in BMD and bone turnover were evident despite the small sample size. These data suggest that postmenopausal women with breast cancer completing tamoxifen

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American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors as Adjuvant Therapy for Women With Hormone Receptor–Positive Breast Cancer: Status Report 2002

Abstract: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Cited by 217 publications

References 36 publications

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease

Biological reprogramming in acquired resistance to endocrine therapy of breast cancer

Prevention of Bone Loss After Withdrawal of Tamoxifen

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