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Putative biomarkers of tamoxifen response in breast cancer
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Putative biomarkers of tamoxifen response in breast cancer
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Putative biomarkers of tamoxifen response in breast cancer
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Dissertation
Putative biomarkers of tamoxifen response in breast cancer
2011
Overview
Several molecular factors have been associated with the sensitivity of breast cancer to tamoxifen (T): Pax2 can mediate the repression of ERBB2 expression by the tamoxifen-ER complex; TC21 is a member of the Ras superfamily associated with increased recurrence in tamoxifen-treated patients; CCND1 (Cyclin D1) is frequently amplified in breast cancers resistant to this drug; and RSF1 is often co-amplified with CCND1 on chromosome 11q. Here, validation of the predictive value of these biomarkers is explored in the MA.12 trial, in which premenopausal women with node-positive/high-risk node-negative early breast cancer, of any hormonal status, were randomized to T (20 mg/day) or P for 5 years after receiving adjuvant chemotherapy. Overall survival (OS) and relapse-free survival (RFS) were evaluated. Pax2 and TC21 (measured via IHC) expression were not associated with OS or RFS. However, in the ER+ subgroup, patients with low TC21 expression derived greater benefit from T compared with P than patients with high TC21 expression, as measured by RFS. No significant interaction with treatment was observed with CCND1 or RSF1 amplification (measured via FISH), although patients with high RSF1 copy number showed a trend toward no benefit from T. Although none of the 4 biomarkers for T response were completely validated in this clinical trial, the predictive effect of TC21 expression and RSF1 amplification deserve further study.
