000			04005nam a22006497a 4500
008			240807s20242024 xxu||||| |||| 00| 0 eng d
022			_a0022-4804
024			_aS0022-4804(24)00202-6 [pii]
040			_aOvid MEDLINE(R)
099			_a38776577
245			_aWhat Proportion of BRCA-Associated Breast Cancer Is Human Epidermal Growth Factor 2-Low and Eligible for Additional Targeted Therapy?.
251			_aJournal of Surgical Research. 299:217-223, 2024 Jul.
252			_aJ Surg Res. 299:217-223, 2024 Jul.
253			_aThe Journal of surgical research
260			_c2024
260			_fFY2024
260			_p2024 Jul
265			_sppublish
265			_tMEDLINE
266			_d2024-08-07
266			_z2024/05/22 18:00
520			_aCONCLUSIONS: A significant portion of gBRCA1/2 patients who were previously diagnosed with TNBC or HR+/HER2- breast cancer would now be classified as HER2-low and could be considered for the use of trastuzumab deruxtecan in the metastatic setting. Outcome differences from therapy changes in this cohort should now be assessed. Copyright © 2024 Elsevier Inc. All rights reserved.
520			_aINTRODUCTION: DESTINY B04 provided clinical meaning to a new classification of human epidermal growth factor 2 (HER2) expression in breast cancer: HER2-low. Patients with germline breast cancer type 1 gene pathogenic variants (gBRCA1) often develop triple negative breast cancer (TNBC), but the proportion who could be classified as HER2-low and qualify for an additional targeted therapy option is unknown. This study aims to characterize the proportion of gBRCA1 or germline breast cancer type 2 gene pathogenic variants patients for whom these novel targeted therapies may be an option.
520			_aMETHODS: We performed a retrospective chart review of patients with gBRCA1/2 treated at our institution for invasive breast cancer from 2000 to 2021. Synchronous or metachronous contralateral breast cancers were recorded separately. HER2 status was determined by immunohistochemistry and fluorescence in situ hybridization. We excluded patients without complete HER2 data.
520			_aRESULTS: Among the 95 breast cancers identified in our cohort of 85 gBRCA1/2 patients, 41 (43%) were TNBC, 38 (40%) were hormone receptor positive (HR+)/HER2-negative, and 16 (17%) were HER2-positive based on standard conventions. We found that 82% of the HR+/HER2-cancers and 66% of TNBCs would be reclassified as HER2-low. After stratifying by BRCA gene status, 64% of cancers in patients with gBRCA1 and 58% of cancers in patients with germline breast cancer type 2 gene pathogenic variants were HER2-low.
546			_aEnglish
650			_a*BRCA1 Protein
650			_a*BRCA2 Protein
650			_a*Molecular Targeted Therapy
650			_a*Receptor, ErbB-2
650			_aAdult
650			_aAged
650			_aBRCA1 Protein/ge [Genetics]
650			_aBRCA2 Protein/ge [Genetics]
650			_aBreast Neoplasms/dt [Drug Therapy]
650			_aBreast Neoplasms/ge [Genetics]
650			_aBreast Neoplasms/pa [Pathology]
650			_aFemale
650			_aGerm-Line Mutation
650			_aHumans
650			_aMiddle Aged
650			_aMolecular Targeted Therapy/mt [Methods]
650			_aReceptor, ErbB-2/an [Analysis]
650			_aReceptor, ErbB-2/ge [Genetics]
650			_aReceptor, ErbB-2/me [Metabolism]
650			_aRetrospective Studies
650			_aTriple Negative Breast Neoplasms/dt [Drug Therapy]
650			_aTriple Negative Breast Neoplasms/ge [Genetics]
650			_zCurated
651			_aMedStar Washington Hospital Center
656			_aHematology/Oncology
657			_aJournal Article
700			_aWhitaker, Kristen _bMWHC
790			_aForester E, Belsare A, Kim DW, Whitaker K, Obeid E, Goldstein LJ, Bleicher RJ, Daly MB, Williams AD
856			_uhttps://dx.doi.org/10.1016/j.jss.2024.04.032 _zhttps://dx.doi.org/10.1016/j.jss.2024.04.032
942			_cART _dArticle
999			_c14563 _d14563