Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial.
OBJECTIVE
To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy.


METHODS
IHC and/or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry. FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival (DFS) after a median 2 years of follow-up.


RESULTS
Central FISH results were available for 2,071 (61%) of the 3,401 patients randomized to the 2 arms. Among patients with FISH-positive disease, (1) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 (95% CI, 0.32 to 0.99) for locally IHC2+ cases (n = 340) and 0.80 (95% CI, 0.40 to 1.61) for centrally IHC2+ cases (n = 299). There was no significant prognostic relationship between (2a) HER2 FISH ratio, (2b) HER2 copy number, or (3) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab.


CONCLUSIONS
There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases. The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy.
Dowsett
Mitch
M
Department of Academic Biochemistry, Royal Marsden Hospital, London, UK. mitch.dowsett@icr.ac.uk
Procter
Marion
M
McCaskill-Stevens
Worta
W
de Azambuja
Evandro
E
Dafni
Urania
U
Rueschoff
Josef
J
Jordan
Bruce
B
Dolci
Stella
S
Abramovitz
Mark
M
Stoss
Oliver
O
Viale
Giuseppe
G
Gelber
Richard D
RD
Piccart-Gebhart
Martine
M
Leyland-Jones
Brian
B
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab