02970nas a2200745 4500000000100000000000100001008004100002260001500043653001200058653002600070653002100096653002000117653003700137653001100174653002600185653001100211653000900222653001500231653001400246653002300260653001700283653001000300653001200310653001800322653001200340653001400352653002300366653002000389100001700409700001700426700001600443700001500459700002000474700001700494700002800511700001500539700001700554700001800571700001900589700002100608700002700629700002100656700001900677700002300696700002100719700002600740700002300766700002300789700002300812700002200835700001600857700002500873700002300898700002000921700002700941700002000968700003300988700001701021700001701038245007901055300001601134490000801150520105201158022001402210 2018 d c2018-01-1110aAnimals10aAntineoplastic Agents10aBreast Neoplasms10aCells, Cultured10aDrug Screening Assays, Antitumor10aFemale10aGenetic Heterogeneity10aHumans10aMice10aMice, Nude10aorganoids10aPrecision Medicine10aTissue Banks10abasal10abiobank10aBreast cancer10aluminal10aorganoids10aPrecision Medicine10atriple negative1 aNorman Sachs1 aJoep de Ligt1 aOded Kopper1 aEwa Gogola1 aGergana Bounova1 aFleur Weeber1 aAnjali Vanita Balgobind1 aKarin Wind1 aAna Gracanin1 aHarry Begthel1 aJeroen Korving1 aRuben van Boxtel1 aAlexandra Alves Duarte1 aDaphne Lelieveld1 aArne van Hoeck1 aRobert Frans Ernst1 aFrancis Blokzijl1 aIsaac Johannes Nijman1 aMarlous Hoogstraat1 aMarieke van de Ven1 aDavid Anthony Egan1 aVittoria Zinzalla1 aJurgen Moll1 aSylvia Fernandez Boj1 aEmile Eugene Voest1 aLodewyk Wessels1 aPaul Joannes van Diest1 aSven Rottenberg1 aRobert Gerhardus Jacob Vries1 aEdwin Cuppen1 aHans Clevers00aA Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity a373-386.e100 v1723 aBreast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion. a1097-4172