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PAM50 provides prognostic information when applied to the lymph node metastases of advanced breast cancer patients

Tobin, Nicholas P. LU ; Lundberg, Arian; Lindström, Linda S.; Harrell, J. Chuck; Foukakis, Theodoros; Carlsson, Lena; Einbeigi, Zakaria; Linderholm, Barbro K.; Loman, Niklas LU and Malmberg, Martin LU , et al. (2017) In Clinical Cancer Research 23(23). p.7225-7231
Abstract

Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting. Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable locoregional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all... (More)

Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting. Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable locoregional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan–Meier and/or multivariate Cox regression analyses. Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan–Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer–specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance. Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients.

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Clinical Cancer Research
volume
23
issue
23
pages
7 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:85037647726
  • wos:000416908200010
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-17-2301
language
English
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yes
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b277fc24-f2d8-4077-8cee-842e0df981cb
date added to LUP
2018-01-11 14:05:01
date last changed
2018-01-16 13:29:43
@article{b277fc24-f2d8-4077-8cee-842e0df981cb,
  abstract     = {<p>Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting. Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable locoregional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan–Meier and/or multivariate Cox regression analyses. Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P &lt; 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan–Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer–specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance. Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients.</p>},
  author       = {Tobin, Nicholas P. and Lundberg, Arian and Lindström, Linda S. and Harrell, J. Chuck and Foukakis, Theodoros and Carlsson, Lena and Einbeigi, Zakaria and Linderholm, Barbro K. and Loman, Niklas and Malmberg, Martin and Fernö, Mårten and Czene, Kamila and Perou, Charles M. and Bergh, Jonas and Hatschek, Thomas and , },
  issn         = {1078-0432},
  language     = {eng},
  month        = {12},
  number       = {23},
  pages        = {7225--7231},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {PAM50 provides prognostic information when applied to the lymph node metastases of advanced breast cancer patients},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-17-2301},
  volume       = {23},
  year         = {2017},
}