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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EThe current evidence to guide adjuvant endocrine therapy in women with ER-positive breast cancer, including tamoxifen, aromatase inhibitors, and ovarian function suppression is reviewed. The studies include ATLAS, aTTom, SOFT, ECOG E3193, TEXT, ABCSG 12, and the Early Breast Cancer Trialists\u2019 Collaborative Group meta-analysis.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Epremenopausal women\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoptimal treatment\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epostmenopausal women\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emortality\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoverall survival\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eestrogen receptor-positive\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group drug\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Etamoxifen\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eletrozole\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EThe current evidence supports at least 5 years of tamoxifen (TAM) or extended adjuvant endocrine therapy (AET) with TAM that is transitioned to an aromatase inhibitor (AI) or 5 years of AI (for postmenopausal women only), stated Nancy E. Davidson, MD, University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh, Pennsylvania. A meta-analysis demonstrated the benefit of TAM for 5 years, and more recent data have shown the benefit of extending the duration to 10 years. However, the results of 4 ongoing trials with AIs are awaited to determine if there is benefit of a longer duration (\u0026gt;\u20095 years) of AI treatment, and results from studies of molecular tests may help predict late recurrence and determine who should receive extended AET.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe Early Breast Cancer Trialists\u2019 Collaborative Group meta-analysis [\u003Cem\u003ELancet\u003C\/em\u003E. 2011] showed that in estrogen receptor (ER)-positive breast cancer (BC), the rate of recurrence was 33% with 5 years of TAM vs 46.2% without TAM at 15 years and the rate of BC mortality was 23.9% and 33.1%, respectively. The 15-year gain for recurrence was 13.0% (log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009\u0026lt;\u2009.00001) and for BC mortality, 9.1% (log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009\u0026lt;\u2009.00001).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe Adjuvant Tamoxifen, Longer Against Shorter trial [ATLAS; Davies C et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2013] in nearly 7000 women with ER-positive BC showed that extending TAM to 10 years, compared with 5 years, was associated with a lower rate of recurrence (21.4% vs 25.1%, respectively; log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.002) and BC mortality (12.2% vs 15.0%, respectively; log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.01). The benefit in ATLAS was similar in all patient subsets. The rates of recurrence and BC mortality were also reduced with 10 vs 5 years of TAM in the Adjuvant Tamoxifen: To Offer More trial [aTTom; Gray RG et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2013 (suppl; abstr 5)]. Recurrence was 28% vs 32%, respectively (log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.003), and BC mortality was 34% vs 35% (log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.2). The combined outcomes in ATLAS and aTTom showed a 15% reduction in mortality and improvement in overall survival (OS) at 15 years with extended AET (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11609\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11609\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11609\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EBreast Cancer Mortality and Overall Survival in the ATLAS and aTTOm Studies\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EExtended AET with letrozole (LET) vs no LET for 5 years in women who had completed 5 years of TAM therapy improved disease-free survival (DFS), with an even greater benefit in the women who were premenopausal at diagnosis and became postmenopausal after TAM therapy [Goss PE et al. \u003Cem\u003EAnn Oncol\u003C\/em\u003E. 2013].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EClinical factors that can guide the decision to extend AET include a higher stage of disease at diagnosis, the absence of or limited toxicity in a given patient, the absence of life-threatening comorbidities, younger age, and patient preference. In the emerging field of molecular biomarkers for late recurrence, a number of molecular tests are being tested and reported.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EThe Breast Cancer Index was shown to predict DFS in years 0 to 5 and \u2265\u20095 years in 2 different patient cohorts [Zhang Y et al. \u003Cem\u003EClin Cancer Res\u003C\/em\u003E. 2013]. The PAM50 Risk of Recurrence Score was shown to predict late recurrence in women who had been recurrence-free at 5 years after diagnosis, with a 50% lower risk of late recurrence in the women who were low risk based on the assay, compared with those who were at moderate or high risk [Sestak I et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EOptimal Treatment in Premenopausal Women\u003C\/h2\u003E\u003Cp id=\u0022p-13\u0022\u003EOvarian function suppression (OFS) in women with BC prior to menopause has been evaluated in clinical studies. The SOFT study [Francis PA et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2014] in 3066 premenopausal women showed that there was no benefit of OFS\u2009+\u2009TAM vs TAM alone for the primary outcome of DFS at the 5.6-year follow-up (86.6% vs 84.7%; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.10). Freedom from BC was greater with OFS\u2009+\u2009TAM (88.4%; HR, 0.81; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.09) and exemestane (EXE)\u2009+\u2009OFS (90.9%; HR, 0.64) compared with TAM alone (86.4%). At 6 years, DFS was greater in women who did vs those who did not have chemotherapy. In the planned analysis of women aged\u2009\u0026lt;\u200935 years, more were BC-free at 5 years in the OFS\u2009+\u2009TAM or EXE\u2009+\u2009OFS group vs TAM alone (78.9%, 83.4%, and 67.7%, respectively).\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EThe ECOG E3193 study in 345 women with ER-positive BC and small node\u2013negative tumors showed that DFS was similar at 9.9 years with OFS\u2009+\u2009TAM and TAM alone (89.7% vs 87.9%; log-rank \u003Cem\u003EP\u2009\u003C\/em\u003E=\u2009.62) [Tevaarwerk AJ et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2014]. OS was also similar at 97.6% and 95.2%, respectively (log-rank \u003Cem\u003EP\u2009\u003C\/em\u003E=\u2009.67). Dr Davidson noted that this trial was terminated early and that it was not sufficiently powered for these outcomes. However, the quality-of-life measures were worse in the women taking OFS vs those who did not, although this difference seemed to be mitigated over time, and she questioned whether this may be due to the women naturally moving toward menopause or adjusting to the changes.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003ERegarding the role of AIs in women treated with OFS, the joint analysis of the TEXT and SOFT trials showed that EXE\u2009+\u2009OFS vs OFS\u2009+\u2009TAM improved DFS, the BC-free interval, and the disease-free interval, although OS was similar with both treatments (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E) [Pagani O et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2014]. In ER-positive BC, the ABCSG12 trial showed that there was no difference in DFS at 94 months with anastrozole vs TAM (HR, 1.13; 95% CI, 0.88 to 1.45; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.33), but OS was worse with anastrozole vs TAM (HR, 1.63; 95% CI, 1.05 to 1.45; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.03) [Gnant M et al. \u003Cem\u003EAnn Oncol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/11612\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/11612\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11612\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \u003Cp id=\u0022p-16\u0022 class=\u0022first-child\u0022\u003EOutcomes in the Joint Analysis of the TEXT and SOFT Trials\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-21\u0022\u003EBased on these data, Dr Davidson states that there are now several evidence-based options available for AET in premenopausal women. These include TAM for 5 to 10 years, TAM for 5 years with a switch to an AI for 5 years, OFS\u2009+\u2009TAM, or OFS\u2009+\u2009AI. In her view, for patients at low risk, TAM alone for 5 to 10 years is sufficient. For women at higher risk\u2014including those who have had chemotherapy, are aged\u2009\u0026lt;\u200935 years, or have multiple positive nodes\u2014OFS\u2009+\u2009TAM or OFS\u2009+\u2009AI can be considered. The optimal duration of OFS-based therapy is uncertain, and long-term follow-up to determine the toxicity and benefit is needed.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/56\/13.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm322\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzm322\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}