title: Clinical predictors of long-term survival in HER2-positive metastatic breast cancer.
abstract: Prior to availability of anti-HER2 therapies, HER2-positive metastatic breast cancer (MBC) was associated with a poor prognosis. Prospective randomized trials have demonstrated survival benefit from anti-HER2 treatments. Anecdotal observations have suggested that a small but meaningful fraction of patients with HER2-positive MBC may be "exceptional responders" with long survival. We hypothesized that demographic and/or clinicopathologic characteristics can be identified to distinguish short-term from long-term survivors. A retrospective, single-institution review of 168 patients with HER2-positive MBC who received treatment with anti-HER2 therapy in the metastatic setting was performed. Cox proportional hazards analysis was used to assess factors associated with long-term survival. Median overall survival from the time of breast cancer recurrence was 3.9 years (95 % CI 3.4-5.2). From the time of diagnosis of MBC, 56 (33 %) survived for 5 or more years and 12 (7 %) survived more than 10 years. Of the 66 patients diagnosed with central nervous system metastases, 9 (14 %) survived more than 5 years following that diagnosis. Younger age at diagnosis, lower stage, hormone receptor positive status, and only having one organ involved at diagnosis were associated with longer survival. Four patients discontinued anti-HER2 therapy and are without evidence of progression of disease after a median 7.4 years (0.2-12.0) since stopping therapy. In a cohort of patients with HER2-positive MBC treated primarily with trastuzumab and lapatinib, 7 % of patients were "exceptional responders." Combining these clinical factors with molecular determinants of prolonged survival may provide insights for individualizing treatment selection.
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Murthy
authors.affiliation: Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, SPH II M2525, Ann Arbor, MI, 48109-2029, USA.
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Kidwell
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Schott
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Merajver
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Griggs
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Smerage
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Van Poznak
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.affiliation: Internal Medicine/Hematology/Oncology, University of Michigan Medical School, 1500 East Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA. norahh@med.umich.edu.
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D000068878:Trastuzumab / Q000008:administration & dosage
chemical_list: D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Brain metastasis; HER2 positive; Metastatic breast cancer; Survival