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Trastuzumab + low dose radiation for HER2+ CNS progression in metastatic breast cancer

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Trastuzumab + low dose radiation for HER2+ CNS progression in metastatic breast cancer

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Breast cancer progression on effective drugs can be challenging to treat. Dr. Beverly Moy discussed how the central nervous system is a particularly challenge in HER2+ metastatic breast cancer. This is an idea for a novel clinical trial using radiation to make trastuzumab more effective based upon that discussion.

Breast cancer progression on effective drugs can be challenging to treat. Dr. Beverly Moy discussed how the central nervous system is a particularly challenge in HER2+ metastatic breast cancer. This is an idea for a novel clinical trial using radiation to make trastuzumab more effective based upon that discussion.

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Trastuzumab + low dose radiation for HER2+ CNS progression in metastatic breast cancer

  1. 1. Clinical Problem: WomenwithmetastaticHER2+ breast cancerrespondwell toHER2-directed therapybuthave poor outcomeswith CNSrelapse,particularlywithCNS carcinomatosisandleptomeningealdisease. Context: There has beenincreasinginterestinusingradiotherapytopotentiate immunotherapybyenhancedantigenpresentation.  Trastuzumabmonoclonal antibodieshave beenusedintrathecallyforCNSrecurrence. (Figuraet al,Bousquetetal)  Data from neoadjuvant chemotherapy+Her2therapy trialssuggestimmune responseplaysan importantrole - tumorinfiltratinglymphocytesare associatedwithpCRandevent-free survival (Salgadoetal,Denkertetal)  Some data suggestthatbetterHER2 expressionmayimprove response toHER2-directed therapy inmetastaticbreastcancer (Scaltriti etal,Nishimuraetal,Montemurroetal)  Patientswithbrainmetastasesmayhave higherexpressionbothof HER2 and p95 comparedto womenwithnonmetastaticbreastcancer(Duchnowskaetal)  Ionizingradiationcanupregulate HER-2antibodytargetsforbreastcancer,inHER2+ andtriple- negative breastcancercell lines andcanenhance cell kill effectsof trastuzumab (Wattenberget al).  Most interesthasbeeninstereotacticradiation(Muranoetal) butfocal therapy maynot apply well forbreastCNScarcinomatosis inpatientsoftenpreviouslytreated  Low-dose radiationhasbeenusedtopotentiate systemicchemotherapyinheadandneck cancer (Arnoldetal) Hypothesis: Low-dose radiationpriortointrathecal trastuzumabmayinduce HER2expressionand improve treatmentefficacyinwomenwithHER2+CNScarcinomatosis. Proposal: Phase I/IIdose escalationtrial administeringMRI-directedradiationtherapy24-48hours before weeklyITtrastuzumabat50 cGy x 10 weeks,100 cGy levelsx 10 weeks, 150 cGy x 5 (everyotherweek),200cGy x 5 (everyotherweek) Endpoints:Response rates,CNSprogressionfreesurvival

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