{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:18:38Z","timestamp":1773332318464,"version":"3.50.1"},"reference-count":51,"publisher":"American Association for Cancer Research (AACR)","issue":"12","funder":[{"name":"Institut Jules Bordet","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Institut Jules Bordet","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HER2+ early breast cancer is a heterogeneous disease, comprising all the intrinsic breast cancer subtypes. The only biomarker available nowadays for anti-HER2 treatment selection is HER2 status itself, but estrogen receptor (ER) status is emerging as a robust predictive marker within HER2+ disease. In this Perspective, we discuss the biological and clinical differences between patients with HER2+\/ER-positive (ER+) disease versus those with HER2+\/ER-negative (ER-neg) tumors, namely, short-term and long-term (&amp;gt;5 years after diagnosis) prognosis, response to neoadjuvant treatment and benefit from adjuvant anti-HER2\u2013targeted therapies. We also address other possible biomarkers to be used for patient selection in future clinical trials, such as gene signatures, PAM50 subtypes, tumor-infiltrating lymphocytes, PIK3CA mutations, and changes in Ki67 score during treatment and discuss their limitations. Finally, we suggest new clinical trial designs that can have an impact on clinical practice, aiming to test treatment deescalation separately for patients with HER2+\/ER+ and HER2+\/ER-neg tumors. We also propose an integrated classification of HER2+ disease, comprising DNA, RNA, protein expression, and microenvironment characteristics, in order to identify those tumors that are truly \u201cHER2-addicted\u201d and may benefit the most from anti-HER2 treatment.<\/jats:p>","DOI":"10.1158\/1078-0432.ccr-19-2612","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T20:25:13Z","timestamp":1581452713000},"page":"2783-2788","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["What Is the Real Impact of Estrogen Receptor Status on the Prognosis and Treatment of HER2-Positive Early Breast Cancer?"],"prefix":"10.1158","volume":"26","author":[{"given":"Mariana","family":"Brand\u00e3o","sequence":"first","affiliation":[{"name":"1Institut Jules Bordet and Universit\u00e9 Libre de Bruxelles (U.L.B.), Boulevard de Waterloo 121, 1000, Brussels, Belgium."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5573-0711","authenticated-orcid":false,"given":"Rafael","family":"Caparica","sequence":"additional","affiliation":[{"name":"1Institut Jules Bordet and Universit\u00e9 Libre de Bruxelles (U.L.B.), Boulevard de Waterloo 121, 1000, Brussels, Belgium."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-2997","authenticated-orcid":false,"given":"Luca","family":"Malorni","sequence":"additional","affiliation":[{"name":"2\"Sandro Pitigliani\" Oncology Department and Translational Research Unit, Hospital of Prato, Via Suor Niccolina, Prato, Italy."}]},{"given":"Aleix","family":"Prat","sequence":"additional","affiliation":[{"name":"3Translational Genomics and Targeted Therapeutics in Solid Tumors, IDIBAPS, Barcelona, Spain."},{"name":"4Medical Oncology Department, Hospital Cl\u00ednic of Barcelona, University of Barcelona, Barcelona, Spain."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-4649","authenticated-orcid":false,"given":"Lisa A.","family":"Carey","sequence":"additional","affiliation":[{"name":"5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina."}]},{"given":"Martine","family":"Piccart","sequence":"additional","affiliation":[{"name":"1Institut Jules Bordet and Universit\u00e9 Libre de Bruxelles (U.L.B.), Boulevard de Waterloo 121, 1000, Brussels, Belgium."}]}],"member":"1086","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2022061101205634100_bib1","doi-asserted-by":"crossref","first-page":"12222","DOI":"10.1038\/ncomms12222","article-title":"A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers","volume":"7","author":"Ferrari","year":"2016","journal-title":"Nat Commun"},{"key":"2022061101205634100_bib2","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/dju152","article-title":"Molecular features and survival outcomes of the intrinsic subtypes within HER2-positive breast 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