Abstract
BackgroundA considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer.MethodsWe performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group).ResultsPotential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052).ConclusionOur array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples.
Highlights
A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice
The counts of loss or gain vs. no change were summarized by tumor group for each bacterial artificial chromosome (BAC), providing 2 x 2 tables for analysis
Chi-square analysis was applied to these tables to test for a significant difference in the distribution of loss or gain vs. no change between tumor groups (Recurrence and Non-recurrence) for each BAC
Summary
A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. The incidence of breast cancer has been rapidly increasing in Korea and it has been the most frequent malignancy in Korean women since 2002 [1]. Breast cancer is a highly heterogeneous disease both histologically and molecularly, and hormone receptor-positive and -negative tumors are quite distinct biologically. Recent gene expression profiling has identified hormone receptors as a fundamental parameter for distinguishing breast cancers, suggesting a molecular difference according to hormone receptor status [2]. A substantial proportion of patients expressing ER either fail to respond initially or become progressively resistant to endocrine therapies [3]. It would be ideal to predict therapeutic efficacy for each patient before treatment is initiated
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