title: Long-term hazard of recurrence in HER2+ breast cancer patients untreated with anti-HER2 therapy.
abstract: BACKGROUND
  Worldwide, many patients with HER2+ (human epidermal growth factor receptor 2-positive) early breast cancer (BC) do not receive adjuvant trastuzumab. Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described.
  
  
  METHODS
  Using data from 1,260 patients randomized to placebo in the adjuvant TEACH trial, we report 10-year annual hazards of recurrence in HER2+ patients not treated with anti-HER2 therapy.
  
  
  RESULTS
  Disease-free survival (DFS) was 75% after 5 and 61% after 10 years, respectively. Patients with HER2+ hormone receptor-positive (HR+ (hormone receptor-positive); ER+ (estrogen receptor-positive) or PR+ (progesterone receptor-positive)) disease had a significantly better DFS than patients with HER2+ HR- (ER-/PR-) disease (hazard ratio 0.72, P=0.02). This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2+ HR- compared to HER2+ HR+ patients, with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients (hazard ratio 0.59, P=0.002 for years 1 to 5). The high early risk of recurrence of HER2+ HR- patients declined sharply over time, so that it was similar to that seen in HER2+ HR+ patients in years 6 to 10 (hazard ratio 0.97, P=0.92 for years 6 to 10).
  
  
  CONCLUSIONS
  Our results show that outcomes in HER2+ patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression. The very high early risk of relapse seen in HER2+ HR- patients is particularly relevant in health care settings with limited access to adjuvant anti-HER2 treatment. The event rates shown for subpopulations of HER2+ BC patients suggest that in resource-constrained environments patients with HER2+ HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy.
authors.affiliation: Center for Oncology and Hematology, Wilhelminen Hospital, Montleartstrasse 37, Vienna, 1160, Austria. kathrin.strasserweippl@gmail.com.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Strasser-Weippl
authors.affiliation: Massachusetts General Hospital Biostatistics Center, 50 Staniford Street, Boston, MA, 02478, USA. nhorick@partners.org.
authors.forename: Nora
authors.initials: N
authors.lastname: Horick
authors.affiliation: Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK. ian.smith@rmh.nhs.uk.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.affiliation: Baylor Sammons Cancer Center, Texas Oncology, US Oncology, 3410 Worth Street, Dallas, TX, 75246, USA. Joyce.OShaughnessy@usoncology.com.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Rigshospitalet, DBCG Secretariat, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. ejlertsen@dadlnet.dk.
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: Mater Hospital, 25 Rocklands Road, North Sydney, NSW 2060, Australia. franb@bigpond.net.au.
authors.forename: Frances
authors.initials: F
authors.lastname: Boyle
authors.affiliation: University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. abuzdar@mdanderson.org.
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.affiliation: Centre GF Leclerc, 1 Rue du Professeur Marion, 21000, Dijon, France. pfumoleau@cgfl.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.affiliation: Northwestern University, 633 Clark Street, Chicago, IL, 60208, USA. WGradishar@nmff.org.
authors.forename: William
authors.initials: W
authors.lastname: Gradishar
authors.affiliation: Hospital Universitario Gregorio Marañón, Universidad Complutense, Ciudad Universitaria, s/n, 28040, Madrid, Spain. mmartin@geicam.org.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.affiliation: Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA. bmoy@partners.org.
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121, 1000, Brussels, Belgium. martine.piccart@bordet.be.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart-Gebhart
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. kathy.pritchard@sunnybrook.ca.
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Arizona Oncology, US Oncology, 3700 W. State Route 89A, Sedona, AZ, 86336, USA. deborah.lindquist@usoncology.com.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lindquist
authors.affiliation: GlaxoSmithKline, 1250 S Collegeville Road, Collegeville, PA, 19426, USA. erica.2.rappold@gsk.com.
authors.forename: Erica
authors.initials: E
authors.lastname: Rappold
authors.affiliation: Massachusetts General Hospital Biostatistics Center, 50 Staniford Street, Boston, MA, 02478, USA. dfinkelstein@partners.org.
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Finkelstein
authors.affiliation: Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA. pgoss@partners.org.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone