Abstract
The overexpression or amplification of the human epidermal growth factor receptor 2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3; p < 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6; p = 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0; p = 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0; p = 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (RAD51, HDGF, TPR) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7; p = 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 205-216 |
| Number of pages | 12 |
| Journal | Journal of Neuro-Oncology |
| Volume | 122 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2015 |
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Keywords
- Brain metastasis
- Breast cancer
- HDGF
- HER2
- RAD51
- TPR
ASJC Scopus subject areas
- Clinical Neurology
- Cancer Research
- Oncology
- Neurology
Cite this
Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients. / Duchnowska, Renata; Jassem, Jacek; Goswami, Chirayu Pankaj; Dundar, Murat; Polar, Yesim; Li, Lang; Woditschka, Stephan; Biernat, Wojciech; Sosińska-Mielcarek, Katarzyna; Czartoryska-Arłukowicz, Bogumiła; Radecka, Barbara; Tomasevic, Zorica; Stępniak, Piotr; Wojdan, Konrad; Sledge, George W.; Steeg, Patricia S.; Badve, Sunil.
In: Journal of Neuro-Oncology, Vol. 122, No. 1, 2015, p. 205-216.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients
AU - Duchnowska, Renata
AU - Jassem, Jacek
AU - Goswami, Chirayu Pankaj
AU - Dundar, Murat
AU - Polar, Yesim
AU - Li, Lang
AU - Woditschka, Stephan
AU - Biernat, Wojciech
AU - Sosińska-Mielcarek, Katarzyna
AU - Czartoryska-Arłukowicz, Bogumiła
AU - Radecka, Barbara
AU - Tomasevic, Zorica
AU - Stępniak, Piotr
AU - Wojdan, Konrad
AU - Sledge, George W.
AU - Steeg, Patricia S.
AU - Badve, Sunil
PY - 2015
Y1 - 2015
N2 - The overexpression or amplification of the human epidermal growth factor receptor 2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3; p < 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6; p = 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0; p = 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0; p = 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (RAD51, HDGF, TPR) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7; p = 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.
AB - The overexpression or amplification of the human epidermal growth factor receptor 2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3; p < 0.001; Cohort B: HR 6.1, 95 % CI 1.5–25.6; p = 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4–10.0; p = 0.009; Cohort B: HR 10.0, 95 % CI 2.0–100.0; p = 0.008). A profile including 13 genes was associated with early (≤36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (RAD51, HDGF, TPR) highly predictive of early BM (HR 5.3, 95 % CI 1.6–16.7; p = 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.
KW - Brain metastasis
KW - Breast cancer
KW - HDGF
KW - HER2
KW - RAD51
KW - TPR
UR - http://www.scopus.com/inward/record.url?scp=84925485871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925485871&partnerID=8YFLogxK
U2 - 10.1007/s11060-014-1704-y
DO - 10.1007/s11060-014-1704-y
M3 - Article
VL - 122
SP - 205
EP - 216
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 1
ER -