In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 10516-10516
Abstract:
10516 Introduction: Tamoxifen (TAM) remains widely used in the treatment of all stages of breast cancer. Although the majority of hormone receptor (HR) positive tumors respond to TAM, many of these breast cancers will develop resistance resulting in disease recurrence or progression. Over-expression of HER2 appears to play a role in de novo tamoxifen-resistance. We have demonstrated previously that HR-positive breast cancers exposed to selective estrogen receptor modulators (SERMs), such as tamoxifen, in vivo continue to express HR but have an increase in the expression of HER2 (O'Regan Clin Cancer Res 2006). However the above finding has not been confirmed in patient samples. Materials and Methods: We evaluated 30 paired tissue samples from patients with HR positive tumors whose cancers recurred. The first tissue sample is from diagnosis and the paired sample comes from metachronous metastatic disease. Results: The median age of diagnosis was 56 (29–96). Seven patients presented with stage I disease, 11 with stage II and nine with stage III3, and three patients had missing staging information. The median time to recurrence was three years. The expression of ER decreased from diagnosis to recurrence from 79% to 59% (p=0.035). PR also decreased between diagnosis and recurrence from 34% to 22% (p=0.13). HER2 score was 2 or 3 in 27% of samples at diagnosis and in 53% at time of recurrence (p=0.01). These cancers did not have HER2 gene amplification. Conclusions: These results confirm our in vivo findings that over-expression of HER2 plays a significant role in acquired TAM- resistance. We have previously demonstrated that trastuzumab inhibits growth of SERM-resistant breast cancers in vivo despite the fact that these cancers did not have HER2 gene amplification. Taken together, our findings suggest that trastuzumab should be examined clinically in patients with TAM-resistant metastatic breast cancer, as they may be particularly sensitive to inhibition of HER2-driven pathways. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2007.25.18_suppl.10516
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2007
detail.hit.zdb_id:
2005181-5
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