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17-10-2010 | Oncology | Article

Gene could help predict tamoxifen resistance

Abstract

Free abstract

MedWire News: The breast cancer anti-estrogen resistance 4 gene (BCAR4) could help predict whether a patient with breast cancer will respond to treatment with tamoxifen, Dutch researchers report.

"Our results indicate that patients with high levels of BCAR4 are at increased risk for early recurrence of the disease and have reduced probability of long-term benefit of tamoxifen treatment," write Ton van Agthoven (Erasmus MC-University Medical Center, Rotterdam) and colleagues in the British Journal of Cancer.

Previous studies have identified BCAR4 as a gene involved in anti-estrogen resistance in breast cancer. In the present study, van Agthoven and team aimed to establish it's clinical relevance by investigating the relationship between BCAR4, tamoxifen resistance, and cancer aggressiveness.

They report that BCAR4 mRNA was detected in 81 (29%) of 280 tumor samples from patients with advanced estrogen receptor (ER)-positive primary breast cancer who were receiving tamoxifen monotherapy as first-line treatment.

The 12-month progression-free survival (PFS) rates were 43.2%, 39.0%, and 30.0% among patients with negative, low (below median), and high (above median) BCAR4 mRNA levels, respectively.

Multivariate analyses confirmed that high BCAR4 mRNA levels independently predicted poor PFS (hazard ratio [HR]=1.47).

The presence of BCAR4 mRNA also increased the risk for shorter metastasis-free (HR=1.41) and overall survival (HR=1.77) in a separate cohort of 506 patients with lymph node-negative, ER-positive cancer who were not receiving systemic adjuvant therapy. This reflects tumor aggressiveness, remark van Agthoven and co-authors.

Using a cellular model of breast cancer, the team found that BCAR4 activates v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB)2 and ERBB3 signaling in the presence of estrogen or tamoxifen. Inhibition of the ERBB receptors inhibited cell proliferation, confirming their role in BCAR4-induced tamoxifen resistance.

Therefore, the researchers conclude that patients with high levels of BCAR4 may benefit from ERBB-targeted therapy.

Van Agthoven added: "Preliminary results show that BCAR4 is only active in the cancer cells and not in normal adult tissues. Therefore treatments which fight against BCAR4 may have limited side effects for the patient."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Laura Dean

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