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Body mass index influences the prognostic impact of combined nuclear insulin receptor and estrogen receptor expression in primary breast cancer

Björner, Sofie LU ; Rosendahl, Ann H. LU ; Simonsson, Maria LU ; Markkula, Andrea LU ; Jirström, Karin LU ; Borgquist, Signe LU ; Rose, Carsten LU ; Ingvar, Christian LU and Jernström, Helena LU (2017) In Frontiers in Endocrinology 8(NOV).
Abstract

The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor a (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during... (More)

The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor a (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR+ expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR+ conferred higher recurrence-risk in patients with ER+ tumors, but lower risk in patients with ER- tumors (Pinteraction = 0.003). Normal-weight patients with nuclear InsR+ tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR- tumors (Pinteraction = 0.007). Normal-weight patients with a nuclear InsR-/ER+ tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HRadj 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR-/ER- tumors had the worst prognosis (HRadj 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER+ tumors and in overweight or obese patients with ER- tumors. Normal-weight patients with nuclear InsR-/ER+ tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR-/ER- tumors may benefit from more tailored treatment or weight management.

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publication status
published
subject
keywords
Adjuvant breast cancer treatment, Body mass index, Breast cancer, Estrogen receptor alpha, Nuclear insulin receptor, Prognosis
in
Frontiers in Endocrinology
volume
8
issue
NOV
publisher
Frontiers
external identifiers
  • scopus:85035360727
  • wos:000416331500001
ISSN
1664-2392
DOI
10.3389/fendo.2017.00332
language
English
LU publication?
yes
id
66d8e5b1-ae77-429c-becc-aa45a13f5d65
date added to LUP
2017-12-12 12:44:39
date last changed
2018-01-16 13:27:40
@article{66d8e5b1-ae77-429c-becc-aa45a13f5d65,
  abstract     = {<p>The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor a (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR<sup>+</sup> expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P &lt; 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR<sup>+</sup> conferred higher recurrence-risk in patients with ER<sup>+</sup> tumors, but lower risk in patients with ER<sup>-</sup> tumors (P<sub>interaction</sub> = 0.003). Normal-weight patients with nuclear InsR<sup>+</sup> tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR<sup>-</sup> tumors (P<sub>interaction</sub> = 0.007). Normal-weight patients with a nuclear InsR<sup>-</sup>/ER<sup>+</sup> tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HR<sub>adj</sub> 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR<sup>-</sup>/ER<sup>-</sup> tumors had the worst prognosis (HR<sub>adj</sub> 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER<sup>+</sup> tumors and in overweight or obese patients with ER<sup>-</sup> tumors. Normal-weight patients with nuclear InsR<sup>-</sup>/ER<sup>+</sup> tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR<sup>-</sup>/ER<sup>-</sup> tumors may benefit from more tailored treatment or weight management.</p>},
  articleno    = {332},
  author       = {Björner, Sofie and Rosendahl, Ann H. and Simonsson, Maria and Markkula, Andrea and Jirström, Karin and Borgquist, Signe and Rose, Carsten and Ingvar, Christian and Jernström, Helena},
  issn         = {1664-2392},
  keyword      = {Adjuvant breast cancer treatment,Body mass index,Breast cancer,Estrogen receptor alpha,Nuclear insulin receptor,Prognosis},
  language     = {eng},
  month        = {11},
  number       = {NOV},
  publisher    = {Frontiers},
  series       = {Frontiers in Endocrinology},
  title        = {Body mass index influences the prognostic impact of combined nuclear insulin receptor and estrogen receptor expression in primary breast cancer},
  url          = {http://dx.doi.org/10.3389/fendo.2017.00332},
  volume       = {8},
  year         = {2017},
}