A Real-World-Data Retrospective Cohort Study of Low Estrogen Receptor Positive Early Breast Cancer: Natural History and Treatment Outcomes.

A Real-World-Data Retrospective Cohort Study of Low Estrogen Receptor Positive Early Breast Cancer: Natural History and Treatment Outcomes. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Real-World-Data Retrospective Cohort Study of Low Estrogen Receptor Positive Early Breast Cancer: Natural History and Treatment Outcomes. Shahla Bari, David Boulware, Jiannong Li, Loretta Loftus, Aixa Soyano, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-792365/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Purpose: Estrogen receptor–positive (ER + ) breast cancer (BC) is a heterogeneous disease with an ongoing debate regarding the optimal cutoff point for clinically relevant ER expression. We used a real-world database to assess prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy. Methods: We used a nationwide electronic health record– (EHR-) derived deidentified database. Descriptive statistics were used to evaluate the association between ER expression, tumor characteristics, and treatment patterns among patients with earlystage BC. We used Kaplan-Meier survival curves to estimate relapse-free survival (RFS) and overall survival (OS). To assess an optimal ER expression level cut point, association between ER + expression and clinical outcomes were performed. Results: Among 4697 patients with early-stage BC, 83 (1.76%) had ER + -low BC (ER expression, 1%-9.99%), and 36 (0.8%) had ER + -intermediate BC (10%-19.9%). ER + -low tumors were associated with higher tumor grade, larger size and higher axillary tumor burden than ER + -high tumors (≥ 20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC; 21%) and ER + -low BC (22%) than ER + high tumors (8%). Patients with ER + -low and ER + -intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with ER + -high tumors ( P < .001). Tumors with <20% ER expression were associated with worse outcomes. Conclusions: Patients with ER expression levels < 20% BC have poor clinical outcomes similar to those with TNBC. Cancer Biology Breast cancer estrogen receptor low-positive recurrence free survival Figures Figure 1 Figure 2 Figure 3 Full Text Supplementary Files SupplementarymaterialERCutpointbreastCanceRResTreat.pdf Supplementary Fig 1. Kaplan Meyer curve demonstrating recurrence free survival of ER+ low and ER + Intermediate patients who received ET vs those who did not. Abbreviation- ER+ - low 1-9.99% staining, ER+ -inter, 10-19.99%, ER+ , ET-Endocrine therapy Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-792365","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":77161300,"identity":"d3e9dfa8-231a-459e-98c4-6c7ad9502352","order_by":0,"name":"Shahla Bari","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYDACCQY2hgcMBxgYmBkbH3wACrCxE6MlAayFudlwBkgLM9FaGNjbpHlAIoS0yM9ufvYgoeaOvHk7Y5u0za9t8nzMDIwfPubg1mJw55i5QcKxZ4ZzDjM2W+f23TZsY2Zglpy5DY8WiQQziQS2w4wzgN6/ndtzmxGohY2ZF48W+Rnp3yQS/h22B2ppkLbsuW1PUAvDjRwzicS2w4lALU3SDD9uJxLUYnAjp0wise9ZMlBLs2Fvw+3kNiADr1+ADtsm8eHbHdsZ/McfPvjx57bt/Pbmgx8+4nMYCmBsA5MNxKoHgT+kKB4Fo2AUjIKRAgDOIFLvwc2rfgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-8459-8518","institution":"University of South Florida","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Shahla","middleName":"","lastName":"Bari","suffix":""},{"id":77161301,"identity":"fa355b1d-950d-4320-bd6e-f737f54f528a","order_by":1,"name":"David Boulware","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Boulware","suffix":""},{"id":77161302,"identity":"b23439de-725a-4f36-8d07-b54290ded6a2","order_by":2,"name":"Jiannong Li","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiannong","middleName":"","lastName":"Li","suffix":""},{"id":77161303,"identity":"46befbd2-95cf-41fe-a994-68a18c38e684","order_by":3,"name":"Loretta Loftus","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Loretta","middleName":"","lastName":"Loftus","suffix":""},{"id":77161304,"identity":"fb32af06-97d7-42e4-aede-af93a5ed3a2f","order_by":4,"name":"Aixa Soyano","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aixa","middleName":"","lastName":"Soyano","suffix":""},{"id":77161305,"identity":"31caa384-5ff0-4a94-ac65-a0660e78fda4","order_by":5,"name":"Zena Jameel","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zena","middleName":"","lastName":"Jameel","suffix":""},{"id":77161306,"identity":"e42f6317-1150-43a0-b28d-1aba6922d4ab","order_by":6,"name":"Hung Khong","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hung","middleName":"","lastName":"Khong","suffix":""},{"id":77161307,"identity":"04c5a087-300e-4e49-9867-207a408d2647","order_by":7,"name":"Brian Czerniecki","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Brian","middleName":"","lastName":"Czerniecki","suffix":""},{"id":77161308,"identity":"8627b72d-90d0-4d1f-9b83-39dd63a27697","order_by":8,"name":"Ricardo Costa","email":"","orcid":"https://orcid.org/0000-0002-3303-3234","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ricardo","middleName":"","lastName":"Costa","suffix":""}],"badges":[],"createdAt":"2021-08-08 03:19:42","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-792365/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-792365/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":17427780,"identity":"a9388d86-1908-43fa-a368-1ef7ab479db7","added_by":"auto","created_at":"2022-01-18 15:54:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106472,"visible":true,"origin":"","legend":"\u003cp\u003eClinical outcomes of patients with ER+ and TNBC BCs. Triple negative defined as ER/PR \u0026lt; 1% staining and HER2- (i.e., IHC 0/1+ and non-amplified); ER+ ≥ 1% staining. Abbreviations: Breast cancer, BC; Estrogen Receptor, ER; Human Epidermal growth factor receptor 2, HER2; immunohistochemistry (IHC).\u003c/p\u003e","description":"","filename":"Figure1.ER.TNBC.RFS.OS.KMy.png","url":"https://assets-eu.researchsquare.com/files/rs-792365/v2/45e7e661472c8d6c08fecbf8.png"},{"id":17427782,"identity":"6b9c3551-74f7-4327-9eda-6cb1ffc7075e","added_by":"auto","created_at":"2022-01-18 15:54:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":139440,"visible":true,"origin":"","legend":"\u003cp\u003eClinical outcomes of patients with TN, low-, intermediate- and High-ER+ BCs. Triple negative defined as ER and PR \u0026lt; 1% staining, ER+ - low 1-9.99% staining, ER+ -inter, 10-19.99%, ER+ - high ≥ 20% staining. Abbreviations: Breast cancer, BC; Estrogen Receptor, ER; Human Epidermal growth factor receptor 2, HER2; triple negative, TN.\u003c/p\u003e","description":"","filename":"Figure2.ERlow1.png","url":"https://assets-eu.researchsquare.com/files/rs-792365/v2/307651b37e964c1af7af65fb.png"},{"id":17427783,"identity":"9f2af001-ebce-4eb8-9f21-be4503376cf2","added_by":"auto","created_at":"2022-01-18 15:54:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":120271,"visible":true,"origin":"","legend":"\u003cp\u003eClinical outcomes of patients with ER low positive vs. ER high positive BCs. ER+ - low 1-19.9% staining and ER+- high ≥ 20% staining. Abbreviations: Breast cancer, BC; Estrogen Receptor, ER.\u003c/p\u003e","description":"","filename":"Figure3.New.CutpointERlow1.png","url":"https://assets-eu.researchsquare.com/files/rs-792365/v2/12fef6a5822ce6f4ebca6daf.png"},{"id":18378371,"identity":"c8e8961b-c810-4fa0-851b-814325b84a35","added_by":"auto","created_at":"2022-02-18 19:43:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":525592,"visible":true,"origin":"","legend":"","description":"","filename":"RevisedManuscriptERCutpointsBCResTreat.pdf","url":"https://assets-eu.researchsquare.com/files/rs-792365/v2_covered.pdf"},{"id":17427817,"identity":"9a591793-cf57-4c7c-936e-879b65283614","added_by":"auto","created_at":"2022-01-18 15:54:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":469110,"visible":true,"origin":"","legend":"","description":"","filename":"RevisedManuscriptERCutpointsBCResTreat.pdf","url":"https://assets-eu.researchsquare.com/files/rs-792365/v2_covered.pdf"},{"id":17427781,"identity":"f708fd23-ce48-4126-b4dd-352489bd4a54","added_by":"auto","created_at":"2022-01-18 15:54:03","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":148738,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Fig 1. Kaplan Meyer curve demonstrating recurrence free survival of ER+ low and ER + Intermediate patients who received ET vs those who did not. Abbreviation- ER+ - low 1-9.99% staining, ER+ -inter, 10-19.99%, ER+ , ET-Endocrine therapy\u003c/p\u003e","description":"","filename":"SupplementarymaterialERCutpointbreastCanceRResTreat.pdf","url":"https://assets-eu.researchsquare.com/files/rs-792365/v2/a7baa31a1dd2dd3549895c9e.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eA Real-World-Data Retrospective Cohort Study of Low Estrogen Receptor Positive Early Breast Cancer: Natural History and Treatment Outcomes.\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-792365/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, estrogen receptor, low-positive, recurrence free survival","lastPublishedDoi":"10.21203/rs.3.rs-792365/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-792365/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e Estrogen receptor–positive (ER + ) breast cancer (BC) is a heterogeneous disease with an ongoing debate regarding the optimal cutoff point for clinically relevant ER expression. We used a real-world database to assess prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We used a nationwide electronic health record– (EHR-) derived deidentified database. Descriptive statistics were used to evaluate the association between ER expression, tumor characteristics, and treatment patterns among patients with earlystage BC. We used Kaplan-Meier survival curves to estimate relapse-free survival (RFS) and overall survival (OS). To assess an optimal ER expression level cut point, association between ER + expression and clinical outcomes were performed. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Among 4697 patients with early-stage BC, 83 (1.76%) had ER + -low BC (ER expression, 1%-9.99%), and 36 (0.8%) had ER + -intermediate BC (10%-19.9%). ER + -low tumors were associated with higher tumor grade, larger size and higher axillary tumor burden than ER + -high tumors (≥ 20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC; 21%) and ER + -low BC (22%) than ER + high tumors (8%). Patients with ER + -low and ER + -intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with ER + -high tumors ( P \u0026lt; .001). Tumors with \u0026lt;20% ER expression were associated with worse outcomes. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Patients with ER expression levels \u0026lt; 20% BC have poor clinical outcomes similar to those with TNBC.\u003c/p\u003e","manuscriptTitle":"A Real-World-Data Retrospective Cohort Study of Low Estrogen Receptor Positive Early Breast Cancer: Natural History and Treatment Outcomes.","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2022-01-18 15:54:01","doi":"10.21203/rs.3.rs-792365/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2021-08-12 14:41:29","doi":"10.21203/rs.3.rs-792365/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"41d65d83-f900-49ed-9a24-bf6f406cefd6","owner":[],"postedDate":"January 18th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":9803602,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2022-02-18T19:43:29+00:00","versionOfRecord":[],"versionCreatedAt":"2022-01-18 15:54:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-792365","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-792365","identity":"rs-792365","version":["v2"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}