scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Tumor Proliferation ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Secondary Outcomes ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.

scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Tumor Proliferation ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Secondary Outcomes ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.

scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting on tumor proliferation and clinical outcome in breast cancer patients ─ a randomized trial

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Well Being ◽  
Tumor Proliferation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
C Peptide ◽  
Er Positive ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background Conflicting results have been reported on the influence of carbohydrates in breast cancer. Objective To determine the influence of pre-operative per-oral carbohydrate load on proliferation in breast tumors. Design Randomized controlled trial. Setting University hospital with primary and secondary care functions in South-West Norway. Patients Sixty-one patients with operable breast cancer from a population-based cohort. Intervention Per-oral carbohydrate load (preOp™) 18 and 2–4 h before surgery (n = 26) or standard pre-operative fasting with free consumption of tap water (n = 35). Measurements The primary outcome was post-operative tumor proliferation measured by the mitotic activity index (MAI). The secondary outcomes were changes in the levels of serum insulin, insulin-c-peptide, glucose, IGF-1, and IGFBP3; patients’ well-being, and clinical outcome over a median follow-up of 88 months (range 33–97 months). Results In the estrogen receptor (ER) positive subgroup (n = 50), high proliferation (MAI ≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p = 0.038). The CH group was more frequently progesterone receptor (PR) negative (p = 0.014). The CH group had a significant increase in insulin (+ 24.31 mIE/L, 95% CI 15.34 mIE/L to 33.27 mIE/L) and insulin c-peptide (+ 1.39 nM, 95% CI 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (− 0.26 nM; 95% CI − 0.46 nM to − 0.051 nM) compared to the fasting group. CH-intervention ER-positive patients had poorer relapse-free survival (73%) than the fasting group (100%; p = 0.012; HR = 9.3, 95% CI, 1.1 to 77.7). In the ER-positive patients, only tumor size (p = 0.021; HR = 6.07, 95% CI 1.31 to 28.03) and the CH/fasting subgrouping (p = 0.040; HR = 9.30, 95% CI 1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with relapse-free survival of 100% in the fasting group vs. 33% in the CH group (p = 0.015; HR = inf). The CH group reported less pain on days 5 and 6 than the control group (p <  0.001) but otherwise exhibited no factors related to well-being. Limitation Only applicable to T2 tumors in patients with ER-positive breast cancer. Conclusions Pre-operative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2 patients. Trial registration CliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Well Being ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
C Peptide ◽  
Er Positive ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The influence of carbohydrates in breast cancer is conflicting. Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors. Design Randomized controlled trial. Setting University hospital with primary and secondary care functions in South-West Norway. Patients A population-based cohort of 61 patients with operable breast cancer. Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35). Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months). Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being. Limitation Only applicable to ER-positive breast cancer patients with T2-tumors. Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients. Keywords: breast cancer, carbohydrate load, proliferation, insulin, insulin c-peptide, IGF-1, IGFBP3, tumor size, relapse free survival, breast cancer specific survival

scholarly journals Metabolic consequences of perioperative oral carbohydrates in breast cancer patients — an explorative study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Tone Frost Bathen ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Breast Cancer Patients ◽  
Positive Correlation ◽  
Explorative Study ◽  
Er Positive ◽  
Lactate And Pyruvate ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Methods The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n = 25) or standard pre-operative fasting (n = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r = 0.680; p = 0.002). In all tumors (n = 29), glutamate was increased in tumors with high proliferation (t-test; p = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Trial of registration ClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

scholarly journals Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Tone Frost Bathen ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Magic Angle ◽  
Breast Cancer Patients ◽  
Explorative Study ◽  
Er Positive ◽  
Lactate And Pyruvate ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Design: Explorative study. Setting: University hospital with primary and secondary care functions in south-west Norway.Interventions and Outcome Measures: Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n=25) or standard pre-operative fasting (n=35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results: Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n=18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p=0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r=0.680; p=0.002). In all tumors (n=29), glutamate was increased in tumors with high proliferation (t-test; p=0.009), independent of intervention group. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions: Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Registration of trial: CliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT03886389?cond=Breast+cancer+diet&rank=1

Effect of Wnt5a on aggressiveness of ER-positive breast cancer and cancer cell migration through JNK-ALCAM pathway.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11614-11614
Author(s):  
Yoshie Kobayashi ◽  
Takayuki Kadoya ◽  
Ai Amioka ◽  
Noriko Gohda ◽  
Miho Kono ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Mcf7 Cells ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Wnt5a Expression ◽  
Er Positive ◽  
Positive Breast Cancer

11614 Background: Wnt5a is a representative ligand that activates β-catenin-independent pathways and involved in cell motility and cell polarity, and the like, being mediated by JNK. We elucidated the implication of Wnt5a expression in breast cancer. Methods: One hundred seventy eight breast cancer patients (mean age ± SD: 60.0 ± 13.2 years) with clinical Stage I-III between January 2011 and February 2014, were prospectively evaluated. We examined relationships between Wnt5a expression and clinicopathological factors by immunohistochemical analyses. 5-year relapse-free survival rates and sites of recurrence were analyzed. In addition, molecules induced by Wnt5a in cultured cells were identified by DNA microarray analysis. Results: Wnt5a expression was significantly more frequent when estrogen receptor (ER) was present, 68/153 (44%) than when ER was absent, 1/25 (4%) (P <0.001) (Table). In ER-positive breast cancer, a significant interaction between expression of Wnt5a with lymph node metastasis (P<0.001), high nuclear grade (P=0.004), and lymphatic invasion (P=0.001). 5-year relapse-free survival rates were 81.1% and 100% in Wnt5a-positive and Wnt5a-negative breast cancers, respectively (P = 0.024). All recurrent breast cancer patients in this study had bone metastasis. We established MCF7 stably expressing Wnt5a (Wnt5a/MCF7 cells) and microarray analyses identified several genes induced by Wnt5a (>3.0 fold), involving activated leukocyte cell adhesion molecule (ALCAM). ALCAM is known to be related with apoptosis, invasion and prognosis of breast cancer. We focused on ALCAM and investigated its protein expression by Western blotting, and found remarkable increase of ALCAM in Wnt5a/MCF7 cells. Conclusions: Wnt5a expresses in ER-positive breast cancer and is associated with high-grade malignancy and a poor prognosis through JNK-ALCAM pathway. Wnt5a could be a novel prognostic factor of ER-positive breast cancer. [Table: see text]

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

Prognostic significance of immunohistochemical expression of Rb gene product in operable breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21121-21121
Author(s):  
H. Song ◽  
Y. Do ◽  
S. Gang ◽  
S. Kwon ◽  
S. Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Gene Product ◽  
Prognostic Significance ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Metastasis ◽  
Rb Gene

21121 Background: The aim of this study was to investigate the prognostic significance of the expression of Rb gene product in operable invasive breast cancer by performing immunohistochemical analysis. Methods: Between January 1993 and December 2001, 212 operable invasive breast cancer patients underwent immunohistochemical staining for Rb, and we retrospectively analyzed these results together with the clinical outcomes. Results: The overexpression of p53 was detected in 72.7% of the cases. The overexpression of Rb was correlated with positive hormonal receptor (p=0.000), and inversely correlated with lymph node metastasis (p=0.017) and vascular invasion (p=0.004). The tumor size, tumor histology, histologic grade, and tumor stage were not related to the overexpression of p53. Multivariate Cox regression analysis indicate that lymph node metastasis and tumor size were the significant prognostic factors for overall survival; lymph node metastasis was the significant prognostic factor for relapse free survival. On the subgroup analysis, the Rb expressors showed better 7-year overall survival (98.5% vs. 81.5%, respectively, p=0.005) and relapse free survival (94.1% vs. 77.4%, respectively, p=0.021) than did the p53 non-overexpressors for the patients without lymph node metastasis. However, for the patients with lymph node metastasis, the survival rates were not different for both the Rb expressors and the Rb non-expressors. Conclusions: Immunohistochemical staining of the Rb gene product was an independent prognostic factor for predicting survival of the lymph node negative operable breast cancer patients. No significant financial relationships to disclose.

Involvement of NK cell molecular signatures in favorable prognosis of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10565-10565
Author(s):  
Maria Libera Ascierto ◽  
Michael O Idowu ◽  
Yingdong Zhao ◽  
Davide Bedognetti ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Cancer Patients ◽  
Adhesion Molecules ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Activating Receptors

10565 Background: Tumor cell recognition by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with their ligands expressed on tumor cells. In addition, NK cells express adhesion molecules that facilitate formation of the immunological synapse with the tumor targets. Here, we investigated whether the coordinate expression of NK activating receptors and adhesion molecules could provide a signature to segregate breast cancer patients into relapse and relapse-free outcomes. Methods: Gene expression profiling, RT-PCR screening and survival analysis were performed on RNA extracted from primary breast cancers. Tumors were obtained from patients experiencing either 5-8 years relapse-free survival or tumor relapse within 1-3 years following initial treatment. Results: Tumors from patients with a favorable prognosis were characterized by increased expression of genes involved in NK cell interaction with tumor cells and its activation signaling. In particular, up-regulation of Natural Cytotoxicity Receptors (NCRs), leukocyte function-associated antigen 1 (LFA-1), CD226 (DNAM-1) and CD96 was observed in relapse-free patients. Thus, the expression of the NK activating receptors and relevant adhesion molecules involved in NK cell:target interactions can predict relapse free survival in breast cancer patients. Conclusions: Results from the present study, highlighted the effector cooperation between the innate and adaptive immune components within the tumor microenvironment. The NK cells parameters identified in this study, together with the prognostic B and T cell signatures previously reported by us, represent a powerful tool for predicting breast cancer outcome which might be easily introduced in clinical practice.

Sign in / Sign up

Export Citation Format

Share Document