ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer.
OBJECTIVE
We aimed to study the importance of erbB2 status in early stage postmenopausal breast cancer for patients who participated in a trial of five vs. two years of adjuvant tamoxifen.


METHODS
We analysed the erbB2 status of the tumours from 577 patients participating in the trial, either by a DNA amplification assay (n = 181) or by measurement of the protein level with flow cytometry (n = 396).


RESULTS
ErbB2 was overexpressed or gene amplified in 102 of the patients (18%). Overall, erbB2-positive patients had a significantly lower recurrence-free probability than others, 62% at five years as compared to 83%, and showed a significantly decreased breast cancer survival rate (P = 0.0007). ErbB2 status was significantly associated with recurrence and death in Cox multivariate analysis, adjusting for nodal status, tumour size and estrogen receptor status. The relative risk of recurrence (RR) for five vs. two years of tamoxifen was analysed in relation to erbB2 status for patients still disease-free two years after surgery. Whereas erbB2-negative patients showed significant benefit from prolonged treatment (RR = 0.62, 95% confidence interval (95% CI): 0.42-0.93), no benefit was evident for erbB2-positive patients (RR = 1.1, 95% CI: 0.41-3.2). When the same analysis was restricted to ER-positive patients a similar difference in relative hazard was obtained but the difference was not strictly significant (P = 0.065).


CONCLUSIONS
For early stage breast cancer patients treated with adjuvant tamoxifen, overexpression of erbB2 is an independent marker of poor prognosis. The results suggest that overexpression decreases the benefit from prolonged tamoxifen treatment.
Stål
O
O
Department of Biomedicine and Surgery, Linköping University, Sweden. olle.stal@onk.liu.se
Borg
A
A
Fernö
M
M
Källström
A C
AC
Malmström
P
P
Nordenskjöld
B
B
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004273:DNA, Neoplasm / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D017698:Postmenopause; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D013629:Tamoxifen / Q000008:administration & dosage* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm; D005819:Genetic Markers; D013629:Tamoxifen