Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy

Niméus-Malmström, Emma; Ritz, Cecilia; Edén, Patrik; Johnsson, Anders; Ohlsson, Mattias; Strand, Carina; Ostberg, G; Fernö, Mårten; Peterson, Carsten

doi:10.1016/j.ejca.2006.06.031

Cited by 21 publications

(13 citation statements)

References 44 publications

(21 reference statements)

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“…The tissue composition and suboptimal sample collection procedures may also explain the relatively low ratio values obtained in breast cancer, in comparison with other tissue materials. In a recent publication from our group [16], we had approximately the same percentage of samples with poor RNA quality (9%) in comparison with other studies using similar criteria for evaluation of the RNA quality (10–20%) [17,18]. …”

Section: Discussionmentioning

confidence: 82%

RNA quality in frozen breast cancer samples and the influence on gene expression analysis – a comparison of three evaluation methods using microcapillary electrophoresis traces

et al. 2007

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Background: Assessing RNA quality is essential for gene expression analysis, as the inclusion of degraded samples may influence the interpretation of expression levels in relation to biological and/or clinical parameters. RNA quality can be analyzed by agarose gel electrophoresis, UV spectrophotometer, or microcapillary electrophoresis traces, and can furthermore be evaluated using different methods. No generally accepted recommendations exist for which technique or evaluation method is the best choice. The aim of the present study was to use microcapillary electrophoresis traces from the Bioanalyzer to compare three methods for evaluating RNA quality in 24 fresh frozen invasive breast cancer tissues: 1) Manual method = subjective evaluation of the electropherogram, 2) Ratio Method = the ratio between the 28S and 18S peaks, and 3) RNA integrity number (RIN) method = objective evaluation of the electropherogram. The results were also related to gene expression profiling analyses using 27K oligonucleotide microarrays, unsupervised hierarchical clustering analysis and ontological mapping.

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Section: Discussionmentioning

confidence: 82%

RNA quality in frozen breast cancer samples and the influence on gene expression analysis – a comparison of three evaluation methods using microcapillary electrophoresis traces

et al. 2007

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“…NPI compares favorably with many other predictor models (20) and provides information about suitability for chemotherapy. Patients in the low-risk group would normally be candidates for endocrine therapy only, provided that the tumor is estrogen receptor a/progesterone receptor positive.…”

Section: Discussionmentioning

confidence: 99%

Carcinoembryonic Antigen Cell Adhesion Molecule 6 Predicts Breast Cancer Recurrence following Adjuvant Tamoxifen

Maraqa

Cummings

Peter

et al. 2008

Clinical Cancer Research

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Purpose: Tamoxifen remains therapy of choice for premenopausal estrogen receptor a^positive breast cancer. However, resistance and recurrence are serious problems. Our previous work indicated that carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) was significantly upregulated in tamoxifen-resistant (TAMr) MCF-7 derivatives.The aim of this study was to determine the functional role of CEACAM6 in endocrine-resistant breast cancer and to retrospectively test whether it was predictive of resistance in a large cohort of breast cancers with long-term follow-up. Experimental Design: siRNA silencing of CEACAM6 was done in TAMr cells and effects on clonogenicity and endocrine sensitivity were determined. CEACAM6 immunohistochemistry was done on a tissue microarray comprising 108 relapsed primary human breast cancers and 243 tamoxifen-sensitive controls. Results: siRNA-mediated silencing of CEACAM6 reduced both clonogenicity and anchoragedependent and anchorage-independent growth of TAMr cells. Importantly, CEACAM6 silencing restored sensitivity of TAMr cells to 4-hydroxytamoxifen and proliferative response to 17h-estradiol. Immunohistochemistry showed significantly more CEACAM expression in the relapsed group compared with nonrelapsed controls [35 of 108 (33.3%) and 32 of 243 (13.2%), respectively; odds ratio, 3.16 (95% confidence interval, 1.83-5.47); P < 0.0001]. Additionally, we derived an outcome predictor model based on CEACAM expression that restratified patients in the Nottingham prognostic index intermediate-risk group into either higher-risk or lower-risk group. Conclusions: Our data support an important role for CEACAM6 in endocrine resistance, which can serve as a powerful predictor of future recurrence.For the last three decades, tamoxifen (TAM) has been the principal endocrine therapy for estrogen receptor a -positive breast cancer patients in both the primary and adjuvant settings and still remains the choice of endocrine therapy in the premenopausal setting (1, 2). However, resistance and recurrence remain a serious problem, with data from clinical studies showing that most patients eventually acquire tamoxifen resistance (3).To elucidate the mechanisms of recurrence following adjuvant endocrine therapy, an expression microarray study by our group showed that carcinoembryonic cell adhesion molecule 6 (CEACAM6) was significantly up-regulated by 20-fold in tamoxifen-resistant (TAMr) MCF-7 derivatives compared with sensitive parental controls (4). CEACAM6 is overexpressed in several human cancers including colorectal adenomas (5) and carcinomas (6), gastric cancers (7), and pancreatic cancers (8, 9). Moreover, CEACAM6 overexpression in colorectal cancer cells has been correlated with reduced overall survival and disease-free survival (6), and CEACAM6 overexpression in colon cancer cells prevented colonocyte differentiation and promoted tumorigenicity in nude mice (10). In pancreatic cancer cells, CEACAM6 overexpression was associated with anoikis resistance and in vivo metastasis (9). CEACA...

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“…We hypothesized that primary tumor characteristics, typically used to guide prognosis and treatment [21] would also predict the likelihood of identifying CTCs in patients with operable breast cancer.…”

Section: Introductionmentioning

confidence: 99%

HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer

Lang

Mosalpuria

Cristofanilli

et al. 2008

Breast Cancer Res Treat

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Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy

Cited by 21 publications

References 44 publications

RNA quality in frozen breast cancer samples and the influence on gene expression analysis – a comparison of three evaluation methods using microcapillary electrophoresis traces

RNA quality in frozen breast cancer samples and the influence on gene expression analysis – a comparison of three evaluation methods using microcapillary electrophoresis traces

Carcinoembryonic Antigen Cell Adhesion Molecule 6 Predicts Breast Cancer Recurrence following Adjuvant Tamoxifen

HER2 status predicts the presence of circulating tumor cells in patients with operable breast cancer

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