Quantitation of erbB2 positivity for evaluation of high-risk patients.
BACKGROUND
Because trastuzumab therapy is expected to be effective in a large fraction of erbB2 (HER-2/neu) overexpressing breast cancers, it is important to find the optimal method for evaluation of erbB2 positivity, and the patient group at greatest risk of dying without this therapy.


OBJECTIVE
We evaluated erbB2 immunopositivity in breast cancer with the aim of finding a high-risk group for primary trastuzumab therapy.


METHODS
Three hundred and seventeen samples were evaluated with an immunostaining index. Optimal cut point was systematically tested, and the effect of bcl-2 status on survival in the high-risk group was studied.


RESULTS
Among N+ patients the index value 1.5 reflected the biggest difference in survival. There was a significant correlation between erbB2 positivity and bcl-2 negativity. ErbB2 was a prognosticator among postmenopausal, N+, and postmenopausal N+ patients. In multivariate analysis, erbB2 was the best prognosticator among postmenopausal N+ patients. Six out of seven N+ patients with erbB2 index 1.5 or above died including all postmenopausal patients. Bcl-2 positivity was associated with longer survival in the erbB2 positive patient group.


CONCLUSIONS
The most obvious patients for primary trastuzumab therapy in breast cancer are N+ patients with high erbB2 immunostaining index (> 1.5) and bcl-2 negative immunostaining. In our material 2% of all breast cancer patients fell in this category. This patient group should be selected for testing trastuzumab in the primary treatment.
Jalava
Päivi J
PJ
Department of Pathology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
Kuopio
Teijo
T
Kortelainen
Seppo
S
Kronqvist
Pauliina
P
Collan
Yrjo U I
YU
D000328:Adult; D000368:Aged; 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; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D013997:Time Factors; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab