title: Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006.
abstract: OBJECTIVE
  We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)- amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor (ER) when expressed. In this clinical trial, we sought to translate these findings to patients using targeted therapy without chemotherapy.
  
  
  METHODS
  Women with stages II to III HER2-positive breast cancers were eligible. They received trastuzumab once per week (4 mg/kg loading, then 2 mg/kg) and lapatinib 1000 mg once per day for 12 weeks. Women with ER-positive tumors also received letrozole (plus a luteinizing hormone-releasing hormone [LHRH] agonist if premenopausal). Pathologic response was assessed by ER status. Biopsies were obtained at baseline, weeks 2 and 8, and time of surgery.
  
  
  RESULTS
  Sixty-six patients were enrolled, and 64 were eligible and evaluable for response. Median tumor size was 6 cm (range, 1.5 to 30 cm). Adverse events were mainly grades 1 to 2 (GI, 63%; skin, 46%). Grade 3 metabolic, GI, and liver (18%; 12 patients) and grade 4 liver toxicities (one patient) were also observed. Overall, in-breast pathologic complete response (pCR; ypT0-is) was 27% (ER positive, 21%; ER negative, 36%). The rate of low-volume residual disease (ypT1a-b) was 22% (ER positive, 33%; ER negative, 4%).
  
  
  CONCLUSIONS
  In patients with locally advanced HER2-positive breast cancer, our approach of targeted therapy only resulted in a high pCR rate without chemotherapy. Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy, and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study.
authors.affiliation: Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. rimawi@bcm.edu
authors.forename: Mothaffar F
authors.initials: MF
authors.lastname: Rimawi
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Mayer
authors.forename: Andres
authors.initials: A
authors.lastname: Forero
authors.forename: Rita
authors.initials: R
authors.lastname: Nanda
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Goetz
authors.forename: Angel A
authors.initials: AA
authors.lastname: Rodriguez
authors.forename: Anne C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Susan G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez
authors.forename: Rachel
authors.initials: R
authors.lastname: Schiff
authors.forename: C Kent
authors.initials: CK
authors.lastname: Osborne
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology / Q000601:surgery; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage; D015854:Up-Regulation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000068878:Trastuzumab; D014230:Triazoles; C508053:ERBB2 protein, human