Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 10069
© 2006 American Society of Clinical Oncology

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Abstract

Neuregulin (NRG) expression modulates clinical response to trastuzumab in patients with metastatic breast cancer (MBC)

Universidad de Salamanca, Salamanca, Spain; Hospital Universitario de Salamanca, Salamanca, Spain; Vall d’Hebron University Hospital, Barcelona, Spain; Hospital Universitario Rio Hortega, Valladolid, Spain

10069

Background: ErbB2 overexpression is the major determinant of response to trastuzumab (Herceptin, H). Recently, some authors have reported the potential role of the expression of NRG on ErbB2 activation in breast cancer cells, and its consequences in response to treatment with H. In the present study we analyze the relationship between response to H and expression of ErbB2 and NRG in patients (pt) with MBC. Methods: Data and frozen tissue samples from 30 consecutive pt with MBC and positive ErbB2 at diagnosis [Immunohistochemistry (IHC)] were collected. All pt were treated with an Herceptin-based regimen. Central Pathologic review of ErbB2 expression was performed in all samples (Herceptest and FISH). NRG expression was studied by IHC on paraffin embedded material and by Western blotting on frozen tissue using an antibody raised against the intracellular domain of NRG. NRG expression by IHC was evaluated using a semiquantitative scoring system that assesses both extension and intensity of cytoplasmic staining. Correlation between ErbB2 and NRG expression and its influence in response to H was analyzed. Characteristics of pt: Median Age: 54; Median mts sites: 2; Treatment: H alone:1 pt; H+Taxol:15 pt; H+Taxol+Carbo: 4 pt; H+Taxol+Lip.Doxorub:2 pt, H+Vinorelbine:7 pt; H+CDDP:1 pt. Results: ORR: 76% (CR:23%, PR:53%). Median TTP: 7.8 m. After central Pathologic review, a total of 20 tumors showed ErbB2 amplification by FISH and 19 of them were Herceptest 3+. A positive correlation was observed between ErbB2 amplification and NRG expression. All complete responses (n=7) were seen in pt with ErbB2 amplification. Interestingly, in the group of tumors without ErbB2 amplification (n=10), 7 had high NRG expression levels, as assessed by IHC. Six out of these 7 tumors having high levels of NRG expression, exhibited partial responses. NRG expression, in turn, did not have impact on response among ErbB2 amplified tumors. Conclusions: These preliminary results suggest that responses to H regimens in pt with MBC can be seen in pt lacking ErbB2 amplification in presence of high levels of expression of transmembrane ligand NRG. This suggests that the group of pt that may benefit from treatment with H could be broader than currently established. A confirmatory study is ongoing in a larger series.

No significant financial relationships to disclose.

Abstract presentation from the 2006 ASCO Annual Meeting