PMID- 1548522
OWN - NLM
STAT- MEDLINE
DCOM- 19920423
LR  - 20170210
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 10
IP  - 4
DP  - 1992 Apr
TI  - HER-2/neu in node-negative breast cancer: prognostic significance of 
      overexpression influenced by the presence of in situ carcinoma.
PG  - 599-605
AB  - PURPOSE: Amplification and/or overexpression of the HER-2/neu oncogene have been 
      shown to correlate with poor clinical outcome in patients with axillary 
      node-positive breast cancer. In contrast, the prognostic significance of 
      HER-2/neu in node-negative disease is controversial. This study was undertaken to 
      evaluate further the relationship between HER-2/neu and clinical outcome in 
      node-negative disease. PATIENTS AND METHODS: Overexpression of HER-2/neu was 
      evaluated by permanent-section immunohistochemistry in tumors from 613 patients 
      with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients 
      were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the 
      basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were 
      defined as having small (less than 3 cm), ER-positive tumors and were observed 
      without additional treatment after initial surgery. High-risk patients had either 
      ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were 
      randomized to be observed (n = 146) or to receive adjuvant chemotherapy (n = 160) 
      after surgery. RESULTS: The rate of HER-2/neu overexpression was 14.3% in all 
      tumors combined and was higher in invasive carcinomas with (21.5%) than without 
      (11.2%) a significant noninvasive or in situ histologic component (P less than 
      .0001). There was no relationship between overexpression and clinical outcome in 
      the natural history setting of combined low-risk and high-risk patients not 
      receiving adjuvant therapy (n = 453). Based on the reasoning that the influence 
      of HER-2/neu may have been obscured by high-risk features and/or the presence of 
      noninvasive carcinoma, we also analyzed the subset of patients with low-risk 
      lesions not containing a significant in situ component (n = 179). Patients of 
      this group with HER-2/neu-positive tumors showed only 40% disease-free survival 
      (DFS) at 5 years, compared with over 80% in patients with HER-2/neu-negative 
      tumors (P less than .0001). A similar inverse correlation was observed between 
      overexpression and overall survival in the same group of patients (P = .0001). In 
      a separate analysis involving patients receiving adjuvant chemotherapy, those 
      with HER-2/neu-negative tumors showed significantly improved DFS in response to 
      therapy compared with patients with HER-2/neu-positive tumors. CONCLUSION: 
      Overexpression of HER-2/neu is associated with poor clinical outcome in a subset 
      of node-negative patients with small, ER-positive, predominantly invasive tumors 
      and may play a role in resistance to adjuvant chemotherapy.
FAU - Allred, D C
AU  - Allred DC
AD  - Department of Pathology, University of Texas Health Science Center, San Antonio 
      78284-7884.
FAU - Clark, G M
AU  - Clark GM
FAU - Tandon, A K
AU  - Tandon AK
FAU - Molina, R
AU  - Molina R
FAU - Tormey, D C
AU  - Tormey DC
FAU - Osborne, C K
AU  - Osborne CK
FAU - Gilchrist, K W
AU  - Gilchrist KW
FAU - Mansour, E G
AU  - Mansour EG
FAU - Abeloff, M
AU  - Abeloff M
FAU - Eudey, L
AU  - Eudey L
AU  - et al.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
SB  - IM
GS  - HER-2/neu
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinoma in Situ/*genetics/pathology
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - *Proto-Oncogenes
MH  - Survival Analysis
EDAT- 1992/04/01 00:00
MHDA- 1992/04/01 00:01
CRDT- 1992/04/01 00:00
PHST- 1992/04/01 00:00 [pubmed]
PHST- 1992/04/01 00:01 [medline]
PHST- 1992/04/01 00:00 [entrez]
AID - 10.1200/JCO.1992.10.4.599 [doi]
PST - ppublish
SO  - J Clin Oncol. 1992 Apr;10(4):599-605. doi: 10.1200/JCO.1992.10.4.599.