Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine

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Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine. / Jørgensen, Charlotte Lt; Ejlertsen, Bent; Bjerre, Karsten D; Balslev, Eva; Nielsen, Dorte L; Nielsen, Kirsten V.

I: B M C Cancer, Bind 13, 541, 12.11.2013, s. 1-11.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Jørgensen, CL, Ejlertsen, B, Bjerre, KD, Balslev, E, Nielsen, DL & Nielsen, KV 2013, 'Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine', B M C Cancer, bind 13, 541, s. 1-11. https://doi.org/10.1186/1471-2407-13-541

APA

Jørgensen, C. L., Ejlertsen, B., Bjerre, K. D., Balslev, E., Nielsen, D. L., & Nielsen, K. V. (2013). Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine. B M C Cancer, 13, 1-11. [541]. https://doi.org/10.1186/1471-2407-13-541

Vancouver

Jørgensen CL, Ejlertsen B, Bjerre KD, Balslev E, Nielsen DL, Nielsen KV. Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine. B M C Cancer. 2013 nov 12;13:1-11. 541. https://doi.org/10.1186/1471-2407-13-541

Author

Jørgensen, Charlotte Lt ; Ejlertsen, Bent ; Bjerre, Karsten D ; Balslev, Eva ; Nielsen, Dorte L ; Nielsen, Kirsten V. / Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine. I: B M C Cancer. 2013 ; Bind 13. s. 1-11.

Bibtex

@article{455da0391ce641a4a716a889692112e5,
title = "Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine",
abstract = "BackgroundThe purpose of the present study was to retrospectively evaluate whether copy number changes of the genes encoding the ribonucleotide reductase subunit M1 (RRM1) and/or subunit M2B (RRM2B) predict sensitivity to gemcitabine administered in combination with docetaxel compared to single agent docetaxel in advanced breast cancer patients.MethodsPrimary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering respectively RRM1 at 11p15.5 and a reference probe covering the centromere of chromosome 11 (CEN-11), and RRM2B at 8q22.3 and a reference probe covering the centromere of chromosome 8 (CEN-8). The assays were validated in a material of 60 normal breast samples. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS according to gene status were investigated by subgroup analyses, and the Wald test was applied. All statistical tests were two-sided.ResultsFISH analysis for both RRM1 and RRM2B was successful in 251 patients. RRM1 and RRM2B aberrations (deletions and amplifications) were observed in 15.9{\%} and 13.6{\%} of patients, respectively. RRM1 aberrations were associated with a decreased OS in the time interval 1.5-7.4 years (hazard ratio = 1.72, 95{\%} confidence interval = 1.05-2.79, P = 0.03). RRM2B aberrations alone or in combination with RRM1 aberrations had no prognostic impact in terms of TTP or OS. RR was not different by gene status. No significant differences were detected in TTP or OS within subgroups according to gene status and chemotherapy regimen.ConclusionsThis study demonstrated the presence of RRM1 and RRM2B copy number changes in primary breast tumor specimens. Nevertheless, we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients.",
keywords = "Faculty of Health and Medical Sciences, Docetaxel, FISH, Gemcitabine, Gene aberrations, Metastatic breast cancer, Ribonucleotide reductase, RRM1, RRM2B",
author = "J{\o}rgensen, {Charlotte Lt} and Bent Ejlertsen and Bjerre, {Karsten D} and Eva Balslev and Nielsen, {Dorte L} and Nielsen, {Kirsten V}",
year = "2013",
month = "11",
day = "12",
doi = "10.1186/1471-2407-13-541",
language = "English",
volume = "13",
pages = "1--11",
journal = "B M C Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine

AU - Jørgensen, Charlotte Lt

AU - Ejlertsen, Bent

AU - Bjerre, Karsten D

AU - Balslev, Eva

AU - Nielsen, Dorte L

AU - Nielsen, Kirsten V

PY - 2013/11/12

Y1 - 2013/11/12

N2 - BackgroundThe purpose of the present study was to retrospectively evaluate whether copy number changes of the genes encoding the ribonucleotide reductase subunit M1 (RRM1) and/or subunit M2B (RRM2B) predict sensitivity to gemcitabine administered in combination with docetaxel compared to single agent docetaxel in advanced breast cancer patients.MethodsPrimary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering respectively RRM1 at 11p15.5 and a reference probe covering the centromere of chromosome 11 (CEN-11), and RRM2B at 8q22.3 and a reference probe covering the centromere of chromosome 8 (CEN-8). The assays were validated in a material of 60 normal breast samples. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS according to gene status were investigated by subgroup analyses, and the Wald test was applied. All statistical tests were two-sided.ResultsFISH analysis for both RRM1 and RRM2B was successful in 251 patients. RRM1 and RRM2B aberrations (deletions and amplifications) were observed in 15.9% and 13.6% of patients, respectively. RRM1 aberrations were associated with a decreased OS in the time interval 1.5-7.4 years (hazard ratio = 1.72, 95% confidence interval = 1.05-2.79, P = 0.03). RRM2B aberrations alone or in combination with RRM1 aberrations had no prognostic impact in terms of TTP or OS. RR was not different by gene status. No significant differences were detected in TTP or OS within subgroups according to gene status and chemotherapy regimen.ConclusionsThis study demonstrated the presence of RRM1 and RRM2B copy number changes in primary breast tumor specimens. Nevertheless, we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients.

AB - BackgroundThe purpose of the present study was to retrospectively evaluate whether copy number changes of the genes encoding the ribonucleotide reductase subunit M1 (RRM1) and/or subunit M2B (RRM2B) predict sensitivity to gemcitabine administered in combination with docetaxel compared to single agent docetaxel in advanced breast cancer patients.MethodsPrimary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering respectively RRM1 at 11p15.5 and a reference probe covering the centromere of chromosome 11 (CEN-11), and RRM2B at 8q22.3 and a reference probe covering the centromere of chromosome 8 (CEN-8). The assays were validated in a material of 60 normal breast samples. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS according to gene status were investigated by subgroup analyses, and the Wald test was applied. All statistical tests were two-sided.ResultsFISH analysis for both RRM1 and RRM2B was successful in 251 patients. RRM1 and RRM2B aberrations (deletions and amplifications) were observed in 15.9% and 13.6% of patients, respectively. RRM1 aberrations were associated with a decreased OS in the time interval 1.5-7.4 years (hazard ratio = 1.72, 95% confidence interval = 1.05-2.79, P = 0.03). RRM2B aberrations alone or in combination with RRM1 aberrations had no prognostic impact in terms of TTP or OS. RR was not different by gene status. No significant differences were detected in TTP or OS within subgroups according to gene status and chemotherapy regimen.ConclusionsThis study demonstrated the presence of RRM1 and RRM2B copy number changes in primary breast tumor specimens. Nevertheless, we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients.

KW - Faculty of Health and Medical Sciences

KW - Docetaxel

KW - FISH

KW - Gemcitabine

KW - Gene aberrations

KW - Metastatic breast cancer

KW - Ribonucleotide reductase

KW - RRM1

KW - RRM2B

U2 - 10.1186/1471-2407-13-541

DO - 10.1186/1471-2407-13-541

M3 - Journal article

C2 - 24215511

VL - 13

SP - 1

EP - 11

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

M1 - 541

ER -

ID: 117437981