HER-2/neu status of primary breast cancer and corresponding metastatic sites in patients with advanced breast cancer treated with trastuzumab-based therapy.
BACKGROUND
The aim of this prospective study was to investigate whether there were changes in HER-2/neu status in newly-developed metastatic lesions following treatment with trastuzumab in advanced breast cancer patients overexpressing HER-2/neu. The utility of serological assays for HER-2/neu in such patients was also studied.


METHODS
Sixteen patients with HER-2/neu-overexpressing tumors (15 were 3+ by immunohistochemistry (IHC) and one 2+ by IHC and positive by the chromogenic in situ hybridization (CISH) test) were included in the study. Fourteen patients underwent biopsy and 2 patients fine-needle aspiration (FNA) of newly-developed metastatic lesions following trastuzumab treatment. All samples were assayed for HER-2 by IHC and by the CISH test. Serial serum HER-2/neu (S-HER-2) levels were measured prior to (baseline values) and during trastuzumab-based treatment by enzyme-linked immunosorbent assay (ELISA) (cut-off point: 10 ng/ml) in all patients. The patients were divided into 2 groups: those with "altered HER-2/neu status" and those with "conserved HER-2/neu status" in the metastatic region.


RESULTS
Six out of the 16 (37%) ("altered HER-2/neu status") newly-developed metastatic lesions lost their HER-2/neu overexpression and scored 0 or +1 by IHC or negative on the CISH test, while in the remaining cases (10/16, 62.5%) ("conserved HER-2/neu status"), the HER-2/neu status was unchanged (+3 by IHC or a positive CISH test). Baseline S-HER-2 levels were elevated in 5 out of 16 patients (3 of "altered HER-2/neu status", 2 of "conserved HER-2/neu status"). The serum HER-2 (S-HER-2) levels declined and returned within the normal ranges in all these 5 patients as a response to trastuzumab treatment. Following the disease progression, the S-HER-2 levels of the 3 patients with "altered HER-2/neu status" remained normal, while those of 2 with "conserved HER-2/neu status" increased. There was no statistically significant difference in the number of chemotherapeutic treatments or the median time of treatment with trastuzumab or chemotherapy between the 2 groups. Time to tumor progression (TTP) was significantly shorter in the "altered HER-2/neu status" patients (median TTP for "altered HER-2/neu status": 9.5 months, and for "conserved HER-2/neu status": 12 months; p <0.001).


CONCLUSIONS
These data suggest that, for most patients with metastatic breast cancer treated with trastuzumab, the HER-2/neu expression as measured by IHC and/or CISH in newly-developed metastatic lesions was unchanged. However, a remarkable percentage of cases lost HER-2/neu overexpression. It is not clear whether this finding implies resistance or sensitivity to trastuzumab.
Pectasides
D
D
Second Department of Internal Medicine-Propaedeutic, Oncology Section, Attikon University Hospital, Athens, Greece. pectasid@otenet.gr
Gaglia
A
A
Arapantoni-Dadioti
P
P
Bobota
A
A
Valavanis
C
C
Kostopoulou
V
V
Mylonakis
N
N
Karabelis
A
A
Pectasides
M
M
Economopoulos
T
T
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000378:metabolism*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab