Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer

2012 ◽  
Vol 139 (3) ◽  
pp. 491-498 ◽  
Author(s):  
Axel Muendlein ◽  
Alois H. Lang ◽  
Simone Geller-Rhomberg ◽  
Thomas Winder ◽  
Klaus Gasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Variant ◽  
Event Free Survival ◽  
Common Genetic Variant ◽  
Her2 Positive ◽  
Free Survival ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Association of a common genetic variant of the IGF1 gene with clinical outcome in patients with HER2-positive breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 193-193
Author(s):  
A. Lang ◽  
A. Muendlein ◽  
B. L. Hartmann ◽  
H. Drexel ◽  
T. Decker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Rare Allele ◽  
Event Free Survival ◽  
Her2 Positive ◽  
Free Survival ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

193 Background: Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Circulating IGF1 levels may be linked with an increased risk of colorectal and breast cancer. Further, IGF1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, recently have been associated with a poor clinical outcome in patients with colorectal cancer. However, the influence of IGF1 SNPs on the prognosis of patients with breast cancer is unknown. Therefore, we aimed at investigating the influence of IGF1 tagging polymorphisms associated with IGF1 levels on event-free survival in patients with HER2-positive breast cancer. Methods: The present study included 161 consecutive white patients with HER2-positive breast cancer treated between 2000 and 2010 at the Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria. Event-free survival was calculated as the time from cancer diagnosis to either relapse or death from any cause. Genomic DNA was extracted from archived formalin-fixed paraffin embedded tumor tissue samples; five IGF1 tagging polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678) were genotyped by SNaPshot assays. Results: Mean follow up period was 4.3 (± 2.5) years. Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.029). Concordantly, in univariate Cox regression analyses the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 2.87 [1.07 –7.70]; p = 0.036). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 2.86 [1.06 –7.71]; p = 0.038). Thus, our results are in concordance with a recent report that the same SNP is associated with poorer clinical outcome in colorectal cancer patients. Other investigated genetic variants of the IGF1 gene were not significantly associated with event-free survival (all p-values > 0.05). Conclusions: For the first time, our study investigates the influence of IGF1 tagging polymorphisms on the clinical outcome of HER2-positive breast cancer patients suggesting SNP rs2946834 as a predictor for reduced event-free survival.

scholarly journals Neoadjuvant Chemotherapy with Docetaxel, Carboplatin and Weekly Trastuzumab Is Active in HER2-Positive Early Breast Cancer: Results after a Median Follow-Up of over 4 Years

Breast Care ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. 323-327 ◽  
Author(s):  
Hans-Christian Kolberg ◽  
Leyla Akpolat-Basci ◽  
Miltiades Stephanou ◽  
Bahriye Aktas ◽  
Carla Verena Hannig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Neoadjuvant Therapy ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Free Survival ◽  
Her2 Positive Breast Cancer ◽  
Disease Free ◽  
Positive Breast Cancer

Introduction: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years. Here we present 4-year follow-up data for a cohort of 78 patients treated with neoadjuvant TCH. Methods: Between 2009 and 2014 we treated 78 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) every 3 weeks (q3w) and trastuzumab (4 mg/kg loading dose then 2 mg/kg) q1w. Lymph node involvement was verified by sentinel lymph node or core-cut biopsy. Patients were diagnosed at a mean age of 55.5 years; 65.4% had hormone receptor-positive tumors, 34.6% presented with grade 3 disease and 51.3% of patients were node positive. Patients were monitored every 2 cycles by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery, trastuzumab was continued q3w up to 1 year. Results: No grade III/IV toxicities occurred and no case of congestive heart failure was observed. Neither dose modifications nor dose delays were necessary. 34 of the 78 patients (43.6%) achieved a pCR, 27 of the 40 node-positive patients (67.5%) experienced nodal conversion. After a median follow up of 48.5 months the disease-free survival (DFS) was 84.6%, the distant disease-free survival (DDFS) was 87.2% and the overall survival (OS) was 91%. Only T stage and nodal status at baseline were found to be significantly associated with survival estimates. Conclusion: The anthracycline-free regimen TCH is effective and safe in the neoadjuvant therapy of HER2-positive breast cancer, yielding DFS, DDFS and OS probabilities comparable to the results of adjuvant trials. Our data support the use of TCH as a neoadjuvant therapy regimen for patients with HER2-positive breast cancer. They also strongly encourage the use of taxanes and platinum salts as the chemotherapy backbone in studies investigating dual blockade with trastuzumab and pertuzumab in the neoadjuvant setting.

scholarly journals Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting

2017 ◽  
Vol 8 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Agnieszka Adamczyk ◽  
Aleksandra Grela-Wojewoda ◽  
Małgorzata Domagała-Haduch ◽  
Aleksandra Ambicka ◽  
Agnieszka Harazin-Lechowska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Signalling Pathway ◽  
Breast Cancer Patients ◽  
Adjuvant Setting ◽  
Her2 Positive ◽  
Free Survival ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer
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