title: Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive breast cancer patients.
abstract: BACKGROUND
  Emerging literature data are showing that a change in human epidermal growth factor receptor (HER2) status adversely affects breast cancer patient's prognosis. The aim of this study was to evaluate the prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without anti-HER2 agents.
  
  
  METHODS
  One hundred and seven consecutive HER2-positive patients were identified from a prospectively maintained database. The first cohort includes 40 patients treated with chemotherapy (CT) alone. The second cohort includes 67 patients treated with neoadjuvant CT plus anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by immunihistochemistry or fluorescence in situ hybridization on pretreatment core biopsy and on surgical specimen after therapy.
  
  
  RESULTS
  The rates of pathologic complete response (pCR) and breast-conserving surgery were higher in the CT + anti-HER2 cohort. A loss of HER2 expression was observed in 40% of the patients with residual disease after CT alone versus 14.7% of the patients after CT + anti-HER2 agents (P = 0.019). Patients not achieving a pCR have a significant increase in the risk of relapse when compared with those achieving a pCR (hazard ratio [HR] 9.55, P = 0.028). Patients with HER2 loss tended to have a higher risk of relapse as comparing to patients with maintained HER2 positivity (HR 2.41, P = 0.063).
  
  
  CONCLUSIONS
  The pCR is confirmed as a powerful predictor of long-term outcome. The rate of HER2 loss is higher in patients receiving neoadjuvant CT without anti-HER2 agents. HER2 status on residual disease after preoperative therapy can be helpful in selecting patients at different risk of relapse, to be included in prospective trial exploring further adjuvant therapy.
authors.affiliation: Istituto Oncologico Veneto IRCCS, University of Padova, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Guarneri
authors.forename: M V
authors.initials: MV
authors.lastname: Dieci
authors.forename: E
authors.initials: E
authors.lastname: Barbieri
authors.forename: F
authors.initials: F
authors.lastname: Piacentini
authors.forename: C
authors.initials: C
authors.lastname: Omarini
authors.forename: G
authors.initials: G
authors.lastname: Ficarra
authors.forename: S
authors.initials: S
authors.lastname: Bettelli
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2 change; breast cancer; discordance; primary systemic therapy; trastuzumab