PMID- 19920100
OWN - NLM
STAT- MEDLINE
DCOM- 20100308
LR  - 20220321
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 23
DP  - 2009 Dec 1
TI  - Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic 
      therapy and survival outcomes.
PG  - 7381-8
LID - 10.1158/1078-0432.CCR-09-1735 [doi]
AB  - PURPOSE: To evaluate HER2 status in residual tumor identified at the time of 
      surgery in patients not achieving a pathologic complete response (pCR) and to 
      determine the effect of alterations in HER2 status on recurrence-free survival 
      (RFS). EXPERIMENTAL DESIGN: Clinicopathologic data for patients with 
      HER2-overexpressing breast cancer receiving neoadjuvant therapy with a taxane, 
      anthracycline, and concomitant trastuzumab between 2004 and 2007 were reviewed. 
      Surgical specimens for patients achieving less than a pCR were assessed to 
      determine if there was enough residual tissue to evaluate posttreatment HER2 
      status. RFS was determined using the Kaplan-Meier method and compared by the 
      log-rank statistic. RESULTS: A pCR was achieved in 72 of the 142 (50.7%) 
      patients. Residual tumor was sufficient to assess posttreatment HER2 status in 25 
      patients. Fluorescence in situ hybridization done on pretreatment specimens 
      confirmed HER2 amplification before beginning therapy. Eight (32.0%) 
      posttreatment tumors were found to be HER2-negative by fluorescence in situ 
      hybridization. At a median follow-up of 37 months (range, 8-56 months), the RFS 
      was significantly better for patients with tumors that retained HER2 
      amplification (87.5% versus 50%, P = 0.04). CONCLUSION: High pCR rates are 
      achieved in patients with HER2-positive breast cancer treated with neoadjuvant 
      trastuzumab in combination with anthracyclines and taxanes. One third of patients 
      with significant residual disease loses HER2 amplification, and this change is 
      associated with poor RFS. Residual tumor identified at the time of surgery should 
      be reassessed for HER2 status, and novel adjuvant therapy strategies need to be 
      studied in this population.
FAU - Mittendorf, Elizabeth A
AU  - Mittendorf EA
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, Texas 77030, USA.
FAU - Wu, Yun
AU  - Wu Y
FAU - Scaltriti, Maurizio
AU  - Scaltriti M
FAU - Meric-Bernstam, Funda
AU  - Meric-Bernstam F
FAU - Hunt, Kelly K
AU  - Hunt KK
FAU - Dawood, Shaheenah
AU  - Dawood S
FAU - Esteva, Francisco J
AU  - Esteva FJ
FAU - Buzdar, Aman U
AU  - Buzdar AU
FAU - Chen, Huiqin
AU  - Chen H
FAU - Eksambi, Sameena
AU  - Eksambi S
FAU - Hortobagyi, Gabriel N
AU  - Hortobagyi GN
FAU - Baselga, Jose
AU  - Baselga J
FAU - Gonzalez-Angulo, Ana M
AU  - Gonzalez-Angulo AM
LA  - eng
GR  - K23 CA121994/CA/NCI NIH HHS/United States
GR  - K23 CA121994-03/CA/NCI NIH HHS/United States
GR  - K23 CA121994-04/CA/NCI NIH HHS/United States
GR  - K99 CA133244/CA/NCI NIH HHS/United States
GR  - 1K99CA133244-01/CA/NCI NIH HHS/United States
GR  - K99 CA133244-01/CA/NCI NIH HHS/United States
GR  - K23 CA121994-02/CA/NCI NIH HHS/United States
GR  - K23 CA121994-01/CA/NCI NIH HHS/United States
GR  - 1K23CA121994-01/CA/NCI NIH HHS/United States
GR  - K99 CA133244-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091117
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Anthracyclines)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Taxoids)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anthracyclines/pharmacology
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/pharmacology
MH  - Breast Neoplasms/*genetics/metabolism/mortality/*therapy
MH  - Cell Line, Tumor
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Neoadjuvant Therapy/*methods
MH  - Receptor, ErbB-2/*genetics/metabolism
MH  - Recurrence
MH  - Taxoids/metabolism
MH  - Trastuzumab
MH  - Treatment Outcome
PMC - PMC2788123
MID - NIHMS146485
EDAT- 2009/11/19 06:00
MHDA- 2010/03/10 06:00
PMCR- 2010/12/01
CRDT- 2009/11/19 06:00
PHST- 2009/11/19 06:00 [entrez]
PHST- 2009/11/19 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 1078-0432.CCR-09-1735 [pii]
AID - 10.1158/1078-0432.CCR-09-1735 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Dec 1;15(23):7381-8. doi: 10.1158/1078-0432.CCR-09-1735. 
      Epub 2009 Nov 17.