title: Prolonged Response to Trastuzumab in a Patient With HER2-Nonamplified Breast Cancer With Elevated HER2 Dimerization Harboring an ERBB2 S310F Mutation.
abstract: In the current genomic era, increasing evidence demonstrates that approximately 2% of HER2-negative breast cancers, by current standard testings, harbor activating mutations of ERBB2. However, whether patients with HER2-negative breast cancer with activating mutations of ERBB2 also experience response to anti-HER2 therapies remains unclear. This case report describes a patient with HER2-nonamplified heavily pretreated breast cancer who experienced prolonged response to trastuzumab in combination with pertuzumab and fulvestrant. Further molecular analysis demonstrated that her tumors had an elevated HER2 dimerization that corresponded to ERBB2 S310F mutation. Located in the extracellular domain of the HER2 protein, this mutation was reported to promote noncovalent dimerization that results in the activation of the downstream signaling pathways. This case highlights the fact that HER2-targeted therapy may be valuable in patients harboring an ERBB2 S310F mutation.
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Saranya
authors.initials: S
authors.lastname: Chumsri
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Jodi
authors.initials: J
authors.lastname: Weidler
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Siraj
authors.initials: S
authors.lastname: Ali
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Sohail
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Gerald
authors.initials: G
authors.lastname: Wallweber
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Lisa
authors.initials: L
authors.lastname: DeFazio-Eli
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chenna
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Angela
authors.initials: A
authors.lastname: DeRidder
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Goicocheal
authors.affiliation: From Mayo Clinic, Jacksonville, Florida; Monogram Biosciences/LabCorp, South San Francisco, California; Foundation Medicine, Cambridge, Massachusetts; and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics* / Q000556:secondary / Q000628:therapy*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D055503:Protein Multimerization; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D019233:Retreatment; D000068878:Trastuzumab / Q000008:administration & dosage*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004958:Estradiol; D000077267:Fulvestrant; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab