title: Trastuzumab Rechallenge After Lapatinib- and Trastuzumab-Resistant Disease Progression in HER2-Positive Breast Cancer.
abstract: BACKGROUND
  Multiple anti-HER2 therapies have improved the outcome for patients with HER2-positive breast cancer. However, optimal management has yet to be established for lapatinib (LAP)- and trastuzumab (Tmab)-resistant disease progression. Data from our institution were reviewed to contribute to the search for best practices.
  
  
  METHODS
  Between June 2009 and March 2013, 74 HER2-positive advanced breast cancer (ABC) patients were treated with LAP with capecitabine (LAPCAP). Patients re-treated with Tmab-based chemotherapies were identified, with a focus on baseline characteristics, chemotherapies, and efficacy. The study focused on the clinical outcomes of 50 patients re-treated with Tmab after LAPCAP-resistant disease progression (LAPCAP-PD), with an assessment of tumor response and clinical benefit (CB). Progression-free survival (PFS) was used as a predictive surrogate marker for the efficacy of Tmab rechallenge.
  
  
  RESULTS
  All patients were pretreated with Tmab- and LAP-based chemotherapies. At a median follow-up of 7.9 months, PFS was 4.6 months, and overall survival was 33.7 months after LAPCAP-PD. Rechallenges with Tmab-based chemotherapies included gemcitabine (GEM) in 23 patients, vinorelbine in 14, taxanes in 5, endocrine treatments in 2, and others. The CB rate was 32%, including complete response for 1, partial response for 3, and > 6 months of stable disease for 12. Although the median PFS was longer for patients treated with microtubule inhibitors (MTIs) than with GEM, various chemotherapies had different efficacy regardless of whether or not previous LAPCAP had CBs.
  
  
  CONCLUSIONS
  Tmab rechallenge combined with not only MTIs but also an antimetabolite agent is effective against some LAPCAP-PD HER2-positive ABC.
authors.affiliation: Breast Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: kazuhiro.araki@jfcr.or.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Araki
authors.affiliation: Breast Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Fukada
authors.affiliation: Division of Pathology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Division of Pathology, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Horii
authors.affiliation: Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Pathology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Division of Pathology, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
authors.affiliation: Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Breast Surgical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.affiliation: Breast Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D000068878:Trastuzumab / Q000008:administration & dosage*
chemical_list: D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Cancer genomic; Combination with various chemotherapies; Continuing multiple anti-HER2 therapies; Heterogeneity; Immune system around tumor microenvironments