Prognostic utility of circulating transforming growth factor beta 1 in breast cancer patients

2012 ◽  
Vol 27 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Heena Dave ◽  
Manoj Shah ◽  
Sunil Trivedi ◽  
Shilin Shukla
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Menopausal Status ◽  
Breast Cancer Patients ◽  
Early Stage Disease ◽  
Unique Challenge ◽  
Tgf Β1

Transforming growth factor betas (TGF-βs) are multifunctional cytokines with a biphasic role in breast tumorigenesis, acting as tumor suppressors at early stages while stimulating tumor progression at later stages (TGF-β switch). Among the 3 human isoforms, TGF-β1 is known to be overexpressed in several tumor types including breast tumors. TGF-β signaling and “crosstalk” in the tumor microenvironment presents a unique challenge and an opportunity to develop novel therapies. We assessed circulating TGF-β1 levels by ELISA in blood samples from 117 previously untreated breast cancer patients in this prospective study to explore the TGF-β switch at the forefront. The levels were correlated with clinicopathological prognosticators like age, menopausal status, nodal status, histological type, histological grade, necrosis, stromal involvement, and survival. Higher mean preoperative serum TGF-β1 was observed in early-stage patients than controls (p=0.05) as revealed by receiver operating characteristic (ROC) analysis. Elevation of TGF-β1 was evident in patients with advanced-stage breast cancer compared with those having early-stage disease (p=0.0001). Prognosticators of an aggressive phenotype were associated with higher TGF-β1 levels, and higher levels thus announced the likelihood of relapse, marking the role of TGF-β1 as a tumor promoter and evidencing the existence of a TGF-β switch. Moreover, higher levels of TGF-β1 shortened the overall survival in breast cancer patients (p=0.010). The results indicate that circulating TGF-β1 may be used as a predictive and prognostic marker in breast carcinoma.

Association of serum levels of the growth factor GP88 with disease progression in breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22021-e22021
Author(s):  
G. Serrero ◽  
K. Tkaczuk ◽  
M. Zhan ◽  
N. Tait ◽  
C. Ilan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Serum Level ◽  
Disease Progression ◽  
Cancer Patients ◽  
Early Stage ◽  
Serum Levels ◽  
P Value ◽  
Breast Cancer Patients ◽  
Early Stage Disease

e22021 Background: The autocrine growth factor GP88 is an important player in breast cancer. GP88 is expressed in human BC tumors in correlation with their tumorigenicity. Increased GP88 expression was associated with anti-estrogen therapy resistance in ER+ cells and Herceptin resistance in Her-2 overexpressing breast tumors. Inhibition of GP88 expression inhibited tumor incidence and growth in nude mice. Immunohistochemical studies have shown that GP88 is expressed in invasive ductal carcinomas (IDC) and that high GP88 expression correlated with increased recurrence and mortality. Since GP88 is found in serum, we hypothesized that GP88 was elevated in the sera of breast cancer patients compared to healthy individuals and that GP88 serum level increases with disease progression. Methods: An IRB approved prospective study was established at the University of Maryland Breast Clinic to determine the serum level of GP88 in breast cancer patients (BC pts). Approximately 5 ml of blood was drawn every three months. GP88 serum concentration was determined in triplicate by human GP88 enzyme immunoassay. 190 BC pts were accrued. Sera from healthy volunteers (HV) were obtained to establish GP88 baseline. BC patient characteristics: Caucasian- 91, African American-92, Asian-6; median age, 51 (range 29- 86), stage I - 48, II - 52, III - 26, IV - 63. Results: Median serum GP88 level was 28.7 ng/ml (range 16.6–38.2) in HV, 40.7 ng/ml (range 6.4–100) in early stage (stage 1 -3) BC pts (p- value = 0.007) and 45.3 ng/ml (range 9.8 to 158.4) in stage 4 BC patients (p- value= 0.0007). Statistically significant increase in serum GP88 level was found in early stages as well as in metastatic disease when compared to HV. In addition, patients that were initially diagnosed with early stage disease but recurred showed a 5 to 10 fold increase in their GP88 serum levels. Conclusions: GP88 serum level is significantly higher in the sera of BC than HV subjects. Moreover, GP88 serum level increased in association with disease recurrence and progression. This study identifies GP88 as a measurable biomarker for disease progression not only at the tissue but also at the serum level. These results are also interesting since GP88 is also a therapeutic target of malignant progression of breast carcinoma. No significant financial relationships to disclose.

Recurrence patterns among T1-2N0 triple-negative breast cancer patients following mastectomy.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 93-93
Author(s):  
Rebekah Young ◽  
Kimberly Gergelis ◽  
Shalom Kalnicki ◽  
Jana Lauren Fox
Keyword(s):  
Breast Cancer ◽  
Retrospective Study ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Early Stage ◽  
Breast Cancer Patients ◽  
Single Institution ◽  
Early Stage Disease ◽  
Increased Risk

93 Background: Women with early-stage TN breast cancers are at increased risk for recurrence (RR) compared to other molecular subtypes, and are often treated with mastectomy without local adjuvant therapy. We wish to evaluate the RR for these women. Methods: In this single institution retrospective study, women with T1-2N0 TN breast cancer who underwent mastectomy between 2008-12 were identified from tumor registry. Adjuvant chemotherapy was allowed, but adjuvant radiotherapy (RT) was excluded. Of 3,000 cases reviewed, 52 women were identified. Median age was 58.5 (30–90). Lesions were high-grade (83%), and T1-2 (47%, 53%). 21 women (42%) had at least 1 risk factor. 5 women were BRCA+. Women underwent total mastectomy or modified radical mastectomy, and the majority (84%) had adjuvant chemotherapy. Results: At a median follow-up of 3.5 years (6-71 months), there were 8 recurrences (15.4%). 3 (5.8% of cohort) were locoregional (LR) only (2 chest wall (CW) and 1 ipsilateral axilla), 6 (11.5%) involved a concurrent LR and distant recurrence, and 2 (3.8%) were distant only. Median time to recurrence was 17.3 months. The isolated LR recurrences (LRR) were at 14, 15.6 and 15.1 months. Most women (41, 78.8%) were alive with NED. 3 were alive with disease, underdoing treatment, and 1 woman was disease free after treatment for CW recurrence. 8 patients (15.4%) are deceased, half from their cancer. On univariate analysis, there was no significant correlation (p>0.05) between age or high-risk features and RR (STATA v 11). Conclusions: T1-2N0 breast cancer patients are believed to have a low RR following mastectomy. TN disease, however, is more aggressive, and the question of irradiating early stage disease after mastectomy has arisen. A single institution, retrospective study found women with T1-2N0 TN disease fare better with BCT that includes RT, compared to mastectomy alone. Other studies have shown no statistical difference in RR between these 2 groups. We found an isolated LRR rate at 3.5 years of 5.8%. Follow-up and ultimately prospective data is needed to determine whether the isolated LRR warrants a change in treatment recommendations for this pt subset.

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