American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors As Adjuvant Therapy for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Status Report 2004

Winer, Eric P.; Hudis, Clifford A.; Burstein, Harold J.; Wolff, Antonio C.; Pritchard, Kathleen I.; Ingle, James N.; Chlebowski, Rowan T.; Gelber, Richard D.; Edge, S.B.; Gralow, Julie R.; Cobleigh, Melody A.; Mamounas, Eleftherios P.; Goldstein, Lori J.; Whelan, Timothy J.; Powles, Trevor J.; Bryant, John; Perkins, Cheryl L.; Perotti, Judy; Braun, Susan; Langer, Amy S.; Browman, George P.; Somerfield, Mark R.

doi:10.1200/jco.2005.09.121

Cited by 840 publications

(474 citation statements)

References 42 publications

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“…Clinical guidelines from the St. Gallen Consensus Conference and the American Society of Clinical Oncology acknowledge the efficacy of AIs over tamoxifen based on the major clinical trials, but they do not clearly distinguish among treatment strategies (upfront or sequential use) [9,10]. In particular, a majority of the 2007 St. Gallen panel suggested the use of an AI sequentially (i.e., after 2-3 years of tamoxifen), while reserving upfront use for higher risk patients, defined as those with 1-3 or more involved nodes and HER-2/neu amplification or patients with 4 or more involved nodes [9].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…Consequently, AIs are now widely recommended as adjuvant endocrine treatment of postmenopausal women with EBC [9,10].…”

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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“…The use of AI as first line endocrine therapy for post-menopausal, estrogen receptor positive breast cancer has increased dramatically over the last few years with the publication of clinical trials suggesting that these compounds may be more effective than the anti-estrogen tamoxifen [4]. Although the AIs are effective, well tolerated drugs, a significant percentage of patients experience disease relapse during AI therapy, suggesting that resistance to this class of compound is a significant problem.…”

Section: Discussionmentioning

confidence: 99%

“…The third-generation AIs (letrozole, exemestane, and anastrozole) inhibit the growth of such tumors by blocking the peripheral conversion of adrenal androgens to estrogens, suppressing circulating 17β-estradiol (E2) concentrations to below that detectable by current conventional methods (low pM range) [2,3]. Although the AIs have proven to be a highly effective therapy for post-menopausal estrogen receptor-positive (ER+) breast cancer, a significant number of patients receiving AIs will relapse within five years of treatment [4]. Thus, a better understanding of the mechanisms of AI resistance may lead to improved predictive markers of response and more effective treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

The androgen metabolite 5α-androstane-3β,17β-diol (3βAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance

Sikora

Cordero

Larios

et al. 2008

Breast Cancer Res Treat

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The aromatase inhibitors (AIs) are used to treat estrogen receptor-positive (ER+) breast tumors in post-menopausal women, and function by blocking the conversion of adrenal androgens to estrogens by the enzyme CYP19 aromatase. Breast cancer patients receiving AI therapy have circulating estrogen levels below the level of detection; however, androgen concentrations remain unchanged. We were interested in studying the effects of androgens on breast cancer cell proliferation under profound estrogen-deprived conditions. Using in vitro models of estrogen-dependent breast cancer cell growth we show that the androgens testosterone and 5α-dihydrotestosterone induce the growth of MCF-7, T47D and BT-474 cells in the absence of estrogen. Furthermore, we demonstrate that under profound estrogen-deprived conditions these breast cancer cells up-regulate steroidogenic enzymes that can metabolize androgens to estrogens. Lastly, we found that the downstream metabolite of 5α-dihydrotestosterone, 5α-androstane-3β,17β-diol (3βAdiol), is estrogenic in breast cancer cells, and induces growth and ER-signaling via activation of ERα. In conclusion, our results show that breast cancer cells deprived of estrogen up-regulate steroidogenic enzymes and metabolize androgens to estrogen-like steroids. The generation of estrogen-like steroids represents a potential mechanism of resistance to aromatase inhibitors.

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“…Similar conclusions were reached in the MA-17 trial with letrozole [95] and the IES trial with exemestane following tamoxifen in early breast cancer [96]. Based on data from these and other multiple, large randomized trials, it was recommended by the American Society of Clinical Oncology (ASCO) technology assessment panel [97] that optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen.…”

Section: The Road To Adjuvant Treatment With Aromatase Inhibitorsmentioning

confidence: 72%

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

Jordan¹,

Brodie²

2007

Steroids

259

183

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The enthusiasm with which the clinical community has embraced the use of antiestrogenic therapy to treat breast cancer is based upon the proven record of success that first the nonsteroidal antiestrogen tamoxifen and then the aromatase inhibitor have demonstrated in clinical trial. The reasons for the enthusiasm are obvious. Antihormonal therapy, particularly aromatase inhibition to create a "no estrogen state" in the postmenopausal breast cancer patient is effective, saves women's lives, is contributing successfully to reducing the national mortality from breast cancer, is relatively cheap and has fewer side effects and easy administration (oral) than any other anticancer strategy. However, the successful application of a therapeutic strategy to block the known growth stimulation property of estrogen in breast cancer was not greeted with such enthusiasm 40 years ago.Estrogen is essential for life. Without the critical role of estrogenic steroids, reproduction would not be possible. Based on emerging knowledge from laboratory studies, the value of modulating the steroid environment during the menstrual cycle was advanced to clinical testing during the 1950's as a means of oral contraception. The results of these studies were to change society forever.The Worcester Foundation for Experimental Biology is the place where Gregory Pincus established the scientific principles necessary to propose clinical testing of the oral contraceptive and M.C. Chang subsequently established the first protocols to perform in vitro fertilization. Simply stated, the Worcester Foundation was, at that time, the world center for steroid endocrinology and reproductive biology. Over the years, hundreds of scientists have trained at the Foundation and subsequently spread their knowledge throughout the world [1]. However, fashions in research change and new opportunities emerge.In 1971, President Nixon made a national commitment to seek a cure for cancer by signing the National Cancer Act. Mahlon Hoagland, the President of the Worcester Foundation, responded to the initiative by appointing Professor Elwood V. Jensen, Director of the Ben May Cancer Research Laboratory at the University of Chicago, to be a member of the Foundation's Scientific Advisory Board. Jensen had discovered the estrogen receptor (ER) as the putative mechanism of estrogen action in its target tissues [2]. The known link between estrogen and breast cancer suggested that "antiestrogenic strategies" might have potential as therapeutic Correspondence to: V. Craig Jordan, v.craig.jordan@fccc.edu. Present Address: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be d...

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American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors As Adjuvant Therapy for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Status Report 2004

Cited by 840 publications

References 42 publications

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

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

The androgen metabolite 5α-androstane-3β,17β-diol (3βAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

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