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1、Yuetal.BMCMedicine(2015)13:254DOI10.1186/s12916-015-0496-zSpotlightonbreastcancerRESEARCHARTICLEOpenAccessMolecularessenceandendocrineresponsivenessofestrogenreceptor-negative,progesteronereceptor-positive,andHER2-negativebreastcancer**Ke-DaYu,Yi-ZhouJiang,Shuang
2、HaoandZhi-MingShaoAbstractBackground:Theclinicalsignificanceofprogesteronereceptor(PgR)expressioninestrogenreceptor-negative(ER–)breastcanceriscontroversial.Herein,wesystemicallyinvestigatetheclinicopathologicfeatures,molecularessence,andendocrineresponsivenessof
3、ER−/PgR+/HER2−phenotype.Methods:Fourstudycohortswereincluded.ThefirstandsecondcohortswerefromtheSurveillance,Epidemiology,andEndResultsdatabase(n=67,932)andFudanUniversityShanghaiCancerCenter(n=2,338),respectively,forclinicopathologicandsurvivalanalysis.Thethirda
4、ndfourthcohortswerefromtwoindependentpubliclyavailablemicroarraydatasetsincluding837operablecasesand483casesundergoingneoadjuvantchemotherapy,respectively,forclinicopathologicandgene-expressionanalysis.CharacterizedgenesdefiningsubgroupswithintheER–/PgR+/HER2–phe
5、notypeweredeterminedandfurthervalidated.Results:ClinicopathologicfeaturesandsurvivaloutcomesoftheER–/PgR+phenotypefellinbetweentheER+/PgR+andER−/PgR−phenotypes,butweremoresimilartoER−/PgR−.AmongtheER−/PgR+phenotype,30%(95%confidenceinterval[CI]17–42%,pooledbyafix
6、ed-effectsmethod)wereluminal-likeand59%(95%CI45–72%,pooledbyafixed-effectsmethod)werebasal-like.WefurtherrefinedthecharacterizedgenesforsubtypeswithintheER−/PgR+phenotypeanddevelopedanimmunohistochemistry-basedmethodthatcoulddeterminethemolecularessenceofER−/PgR+
7、usingthreemarkers,TFF1,CK5,andEGFR.EitherPAM50-definedorimmunohistochemistry-definedbasal-likeER−/PgR+caseshavealowerendocrinetherapysensitivityscorecomparedwithluminal-likeER−/PgR+cases(P<0.0001byMann-WhitneytestforeachstudysetandP<0.0001forpooledstandardizedmea
8、ndifferenceinmeta-analysis).Immunohistochemistry-definedbasal-likeER−/PgR+casesmightnotbenefitfromadjuvantendocrinetherapy(log-rankP=0.61forsufficientversusins
