Overexpression or amplification of the HER-2 oncogene has been associated with poor survival in node positive breast cancers. We, in CALGB, have discovered that despite this worse outcome, those with perturbations of HER-2 significantly benefit from dose intensive adjuvant chemotherapy resulting in a doubling of the 5 year actuarial survival rates. Our analysis suggests that the important agent in this dose interaction is Adriamycin. Equally important is that patients with no abnormalities of HER-2 do not appear to show the same benefit with high dose treatment. Thus the HER-2 status may define the specific agents and doses that are appropriate for this patient subset. We propose to verify and extend these initial findings by assessing the HER-2/dose interactions in a larger data set. We will study the mechanism of this interaction by determining the whether the expression of the neu differentiation factor (NDF), p53, and the expression and amplification of Topoisomerase II and PRAD-1 will contribute to this dose effect. We will also assess the impact of S phase fraction and the levels of circulating HER-2/c-erbB2 extracellular domain on this interaction. To further enhance this approach, we will obtain data sets from the International Breast Cancer Study Group node positive adjuvant trial, and other CALGB adjuvant trials where the HER-2 status is known, to determine whether specific chemotherapeutic agents, such as Adriamycin, are important in this oncogene/dose interaction.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA064061-01
Application #
2106307
Study Section
Special Emphasis Panel (SRC (80))
Project Start
1994-06-10
Project End
1998-03-31
Budget Start
1994-06-10
Budget End
1995-03-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599