2021
Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer
Farahmand S, Fernandez AI, Ahmed FS, Rimm DL, Chuang JH, Reisenbichler E, Zarringhalam K. Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer. Modern Pathology 2021, 35: 44-51. PMID: 34493825, PMCID: PMC10221954, DOI: 10.1038/s41379-021-00911-w.Peer-Reviewed Original ResearchConceptsHER2 statusBreast cancerTreatment responseHER2-positive breast cancerAnti-HER2 agentsPre-treatment samplesNeoadjuvant chemotherapyTrastuzumab therapyClinical outcomesClinical evaluationProtein immunohistochemistryHER2 amplificationTrastuzumab responseTumor stainTreatment selectionTCGA testPathology teamTumor regionCancer featuresCancerPatientsHER2Current standardImmunohistochemistryHematoxylinAlpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer
Vathiotis IA, Moutafi MK, Divakar P, Aung TN, Qing T, Fernandez A, Yaghoobi V, El-Abed S, Wang Y, Guillaume S, Nuciforo P, Huober J, Di Cosimo S, Kim SB, Harbeck N, Gomez H, Shafi S, Syrigos KN, Fountzilas G, Sotiriou C, Pusztai L, Warren S, Rimm DL. Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer. Clinical Cancer Research 2021, 27: 6156-6163. PMID: 34465600, PMCID: PMC8595766, DOI: 10.1158/1078-0432.ccr-21-2103.Peer-Reviewed Original ResearchConceptsDisease-free survivalHER2-positive breast cancerShorter disease-free survivalBreast cancerQuantitative immunofluorescenceEarly-stage HER2-positive breast cancerAlpha-smooth muscle actin expressionAlpha-smooth muscle actinProgesterone receptor statusHigh α-SMA expressionDigital Spatial ProfilerΑ-SMA expressionPromising candidate biomarkerCompanion diagnostic testsMuscle actin expressionDigital spatial profilingCohort validationNeoadjuvant lapatinibAdjuvant trastuzumabReceptor statusClinical trialsUnivariate analysisEstrogen receptorMAIN OUTCOMEΑ-SMA
2020
Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Kos Z, Roblin E, Kim RS, Michiels S, Gallas BD, Chen W, van de Vijver KK, Goel S, Adams S, Demaria S, Viale G, Nielsen TO, Badve SS, Symmans WF, Sotiriou C, Rimm DL, Hewitt S, Denkert C, Loibl S, Luen SJ, Bartlett JMS, Savas P, Pruneri G, Dillon DA, Cheang MCU, Tutt A, Hall JA, Kok M, Horlings HM, Madabhushi A, van der Laak J, Ciompi F, Laenkholm AV, Bellolio E, Gruosso T, Fox SB, Araya JC, Floris G, Hudeček J, Voorwerk L, Beck AH, Kerner J, Larsimont D, Declercq S, Van den Eynden G, Pusztai L, Ehinger A, Yang W, AbdulJabbar K, Yuan Y, Singh R, Hiley C, Bakir MA, Lazar AJ, Naber S, Wienert S, Castillo M, Curigliano G, Dieci MV, André F, Swanton C, Reis-Filho J, Sparano J, Balslev E, Chen IC, Stovgaard EIS, Pogue-Geile K, Blenman KRM, Penault-Llorca F, Schnitt S, Lakhani SR, Vincent-Salomon A, Rojo F, Braybrooke JP, Hanna MG, Soler-Monsó MT, Bethmann D, Castaneda CA, Willard-Gallo K, Sharma A, Lien HC, Fineberg S, Thagaard J, Comerma L, Gonzalez-Ericsson P, Brogi E, Loi S, Saltz J, Klaushen F, Cooper L, Amgad M, Moore DA, Salgado R. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. Npj Breast Cancer 2020, 6: 17. PMID: 32411819, PMCID: PMC7217863, DOI: 10.1038/s41523-020-0156-0.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesEarly TNBCBreast cancerHER2-positive breast cancerTumor-infiltrating lymphocytesLymphocyte distributionStromal tumorsInflammatory cellsPredictive biomarkersTreatment selectionPrognostic toolClinical practiceOutcome estimatesLymphocytesReproducible assessmentTNBCTumorsCancerScoring guidelinesMultiple areasTumor boundariesRisk estimationImpact of discrepanciesRing studiesAssessmentReport on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Amgad M, Stovgaard ES, Balslev E, Thagaard J, Chen W, Dudgeon S, Sharma A, Kerner JK, Denkert C, Yuan Y, AbdulJabbar K, Wienert S, Savas P, Voorwerk L, Beck AH, Madabhushi A, Hartman J, Sebastian MM, Horlings HM, Hudeček J, Ciompi F, Moore DA, Singh R, Roblin E, Balancin ML, Mathieu MC, Lennerz JK, Kirtani P, Chen IC, Braybrooke JP, Pruneri G, Demaria S, Adams S, Schnitt SJ, Lakhani SR, Rojo F, Comerma L, Badve SS, Khojasteh M, Symmans WF, Sotiriou C, Gonzalez-Ericsson P, Pogue-Geile KL, Kim RS, Rimm DL, Viale G, Hewitt SM, Bartlett JMS, Penault-Llorca F, Goel S, Lien HC, Loibl S, Kos Z, Loi S, Hanna MG, Michiels S, Kok M, Nielsen TO, Lazar AJ, Bago-Horvath Z, Kooreman LFS, van der Laak JAWM, Saltz J, Gallas BD, Kurkure U, Barnes M, Salgado R, Cooper LAD. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group. Npj Breast Cancer 2020, 6: 16. PMID: 32411818, PMCID: PMC7217824, DOI: 10.1038/s41523-020-0154-2.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesComputer-aided diagnosticsPotential of machineAssessment of algorithmsInternational Immuno-Oncology Biomarker Working GroupHER2-positive breast cancerBiomarker Working GroupComputational workflowPrognostic workflowsVisual guidelinesTIL assessmentInfiltrating lymphocytesBreast cancerPredictive featuresSolid tumorsInter-reader variabilityWorkflowClinical validationComputational assessmentRipe opportunityComputational methodsReporting guidelinesLymphocytesVisual scoringClinical translation
2014
Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab
Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer 2014, 14: 326. PMID: 24885187, PMCID: PMC4037428, DOI: 10.1186/1471-2407-14-326.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarboplatinChemotherapy, AdjuvantConnecticutFemaleFluorescent Antibody TechniqueHumansNeoadjuvant TherapyPaclitaxelPhosphorylationProteomicsReceptor, ErbB-2Rhode IslandTime FactorsTrastuzumabTreatment OutcomeConceptsLikelihood of responsePhospho-HER2Nab-paclitaxelPathologic responseHER2 levelsAdvanced HER2-positive breast cancerHER2-positive breast cancerCarboplatin combination therapyPreoperative clinical trialPre-surgical settingSingle-agent trastuzumabPathologic complete responseInitiation of treatmentWeeks of treatmentBreast cancer patientsTumor core biopsiesCore biopsy samplesMonoclonal antibody trastuzumabEvaluable patientsNeoadjuvant regimenNeoadjuvant chemotherapyNeoadjuvant therapyNeoadjuvant treatmentComplete responsePreoperative setting