PMID- 16137435
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20151119
IS  - 1526-8209 (Print)
IS  - 1526-8209 (Linking)
VI  - 6
IP  - 3
DP  - 2005 Aug
TI  - Evaluation of clinical outcomes according to HER2 detection by fluorescence in 
      situ hybridization in women with metastatic breast cancer treated with 
      trastuzumab.
PG  - 240-6
AB  - BACKGROUND: We evaluated the influence of HER2 gene amplification, as determined 
      by fluorescence in situ hybridization (FISH), on clinical outcomes (objective 
      response rates, time to disease progression, and overall survival time) in women 
      with metastatic breast cancer treated with trastuzumab in 3 clinical trials. 
      Breast cancer tissue specimens were evaluated using a direct labeled, dual-probe 
      FISH assay. MATERIALS AND METHODS: Specimens with a HER2:CEP17 ratio of > or = 
      2:0 were considered positive for gene amplification. All specimens had previously 
      demonstrated overexpression of HER2 protein at the 2+ or 3+ level by 
      immunohistochemistry using the Clinical Trials Assay. Response rate, time to 
      disease progression, and survival times were then compared between the 
      FISH-positive and FISH-negative cohorts in each of the 3 clinical trials. 
      RESULTS: Informative FISH results were obtained in 765 (96%) of the 799 patients 
      enrolled in the 3 clinical trials. Overall, 596 (78%) were FISH-positive and 169 
      (22%) were FISH-negative. The proportion of FISH-positive patients was comparable 
      in all 3 trials. Clinical benefit from trastuzumab therapy appeared to be 
      restricted to patients with FISH-positive metastatic breast cancer. In each 
      clinical trial, the cohort of FISH-positive patients had higher overall response 
      rates and longer durations of survival compared with FISH-negative patients. 
      CONCLUSION: These data indicate that assessment of HER2 amplification by FISH is 
      the preferred method to select patients for trastuzumab therapy.
FAU - Mass, Robert D
AU  - Mass RD
AD  - Genentech, Inc., South San Francisco, CA 94080, USA.
FAU - Press, Michael F
AU  - Press MF
FAU - Anderson, Steven
AU  - Anderson S
FAU - Cobleigh, Melody A
AU  - Cobleigh MA
FAU - Vogel, Charles L
AU  - Vogel CL
FAU - Dybdal, Noel
AU  - Dybdal N
FAU - Leiberman, Grazyna
AU  - Leiberman G
FAU - Slamon, Dennis J
AU  - Slamon DJ
LA  - eng
GR  - CA48780/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Breast Cancer
JT  - Clinical breast cancer
JID - 100898731
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/*genetics/pathology
MH  - Clinical Trials as Topic
MH  - Disease Progression
MH  - Female
MH  - Genes, erbB-2/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Patient Selection
MH  - Remission Induction
MH  - Retrospective Studies
MH  - Survival Analysis
MH  - Trastuzumab
MH  - Treatment Outcome
EDAT- 2005/09/03 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/09/03 09:00
PHST- 2005/09/03 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/09/03 09:00 [entrez]
AID - S1526-8209(11)70726-1 [pii]
AID - 10.3816/CBC.2005.n.026 [doi]
PST - ppublish
SO  - Clin Breast Cancer. 2005 Aug;6(3):240-6. doi: 10.3816/CBC.2005.n.026.