Value In Early Breast Cancer Research Articles

Detection, significance and potential utility of circulating tumor cells in clinical practice in breast cancer (Review).

Although advances in diagnostic techniques, new therapeutic strategies and personalization of breast cancer (BC) care have improved the survival for a number of patients, BC remains a major cause of morbidity and mortality for women. The study of circulating tumor cells (CTCs) has significant potential in translational oncology since these cells represent promising biomarkers throughout the entire course of BC in patients. CTCs also have notable prognostic value in early BC as well as metastatic BC. Based on current knowledge, it seems that the dynamics of CTCs that change during therapy reflect therapy response, and CTCs could serve as a tool for risk stratification and real-time monitoring of treatment in patients with BC. The question of how to use this information in everyday clinical practice and how this information can guide or change therapy to affect the clinical outcome of patients with BC remains unanswered. The present review aims to discuss current completed and ongoing trials that have been designed to demonstrate the clinical significance of CTCs, offer insights into treatment efficacy and assess CTC utility, facilitating their implementation in the routine management of patients with BC.

Lymphovascular invasion is an independent prognostic factor in breast cancer irrespective of axillary node metastasis and molecular subtypes.

Lymphovascular invasion (LVI) is a well-known poor prognostic factor for early breast cancer. However, the effect of LVI on breast cancer subtype and node status remains unknown. In this study, we aimed to evaluate the clinical significance of LVI on the recurrence and long-term survival of patients with early breast cancer by comparing groups according to the subtype and node status. We retrospectively reviewed the medical records of 4554 patients with breast cancer who underwent breast cancer surgery between January 2010 and December 2017. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors related to the DFS and OS according to the nodal status and breast cancer subtype. During a follow-up period of 94 months, the median OS and DFS were 92 and 90 months, respectively. The LVI expression rate was 8.4%. LVI had a negative impact on the DFS and OS, regardless of the lymph node status. LVI was associated with higher recurrence and lower survival in the luminal A, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes. The Cox proportional hazards model showed that LVI was a significant prognostic factor for both DFS and OS. No correlation has been observed between LVI and the Oncotype Dx results in terms of prognostic value in early breast cancer. LVI is an independent poor prognostic factor in patients with early breast cancer, regardless of the node status and molecular subtype. Therefore, the LVI status should be considered when making treatment decisions for patients with early stage breast cancer; however, further prospective studies are warranted.

Abstract P4-07-11: Prognostic significance of changes in tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio after neoadjuvant chemotherapy in early breast cancer patients

Abstract Introduction. There are still 30-40% of patients with early breast cancer (BC) that relapse after neoadjuvant chemotherapy (NAC). New prognostic biomarkers are needed. Current evidence shows that both markers of antitumor local and systemic immune response, such as tumor infiltrating lymphocytes (TIL) and neutrophil-to-lymphocyte ratio (NLR) have prognostic value in early BC. Most works have evaluated baseline levels, but their variation after NAC might be related to treatment resistance and should be explored.The aim of this study was to simultaneously investigate the prognostic significance of the pre-post-NAC variation of TIL and NLR in patients with early BC.Methods. Retrospective, single-center cohort of 121 patients with early BC treated with NAC between 2001 and 2010. Pre- and post-NAC TIL (CD3+) were assessed by tumor tissue microarrays performed in both diagnostic core-needle biopsy and surgical excision specimens, respectively. Pre- and post-NAC NLR were calculated based on blood tests collected within 1 month of cancer diagnosis and at the moment of surgery, respectively. The change on TIL and NLR after NAC was estimated by calculating the absolute difference of post- and pre- values of these parameters (Δpost-pre). We examined the association between the absolute difference of TIL and NLR (both divided into deciles) and survival outcomes by Cox regression. To represent in Kaplan-Meier curves the combined effect of the change of TIL and NLR in OS, we divided patients into 4 groups, depending on the sign of Δpost-pre values of TIL and NLR: 1) no TIL nor NLR increment after NAC (ΔTIL & ΔNRLpost-pre≤0); 2) no TIL but NLR increment (ΔTILpost-pre≤0, ΔNRLpost-pre>0); 3) TIL but no NLR increment (ΔTILpost-pre>0, ΔNRLpost-pre≤0); and 4) TIL and NLR increment following NAC (ΔTIL & ΔNRLpost-pre>0).Results. 47 (40%) out of 121 patients had pre- and post-NAC values of both NLR and TIL. Patients’ baseline characteristics are shown in Table 1. The median follow-up of this group was 11.5 years (IQR: 10.5 - 12.5 years). At the final follow-up date, overall survival (OS) was 87.2 %. In the univariable analysis, the increase in TIL and NLR after NAC among deciles showed a negative prognostic value for OS (TIL: HR 1.54, 95%CI 1.05-2.26, p=0.026; HR 1.32 95%CI 0.98-1.79, p=0.070). In the multivariable analysis, adjusted by cancer staging after NAC, both the increase of TIL and NLR after NAC among deciles add independent predictive value (TIL: HR 1.53, 95%CI 1.00-2.34, p=0.049; RNL: HR 1.42 95%CI 0.95-2.12, p=0.09).The subpopulation of patients with no TIL increment after NAC (Groups 1&2, N=23) showed the best prognosis, with no deaths at 10 years. Among patients with TIL increment (Groups 3&4, N=22), those with no NLR increment (Group 3, N=5) showed an intermediate prognosis (20% deaths at 10 years), whereas patients with concurrent NLR increment (Group 4, N=17) had the lowest OS (29.4% deaths at 10 years). Differences observed between groups were statistically significant (Log Rank p=0.042).Conclusion. The integrated characterization of TIL and NLR variations after NAC identifies different prognostic subgroups in early BC patients. In our cohort, both the increment of TIL and/or NLR after NAC are associated to a worse prognosis. Future validation of these findings in large, multicenter cohorts might allow treatment optimization by means of new strategies such as immunotherapy. Table 1.Patients’ baseline characteristicsN=47Age (median, range)56 (21, 78)Menstrual statusPostmenopausal25 (53,2%)Premenopausal22 (46,8%)Histologic subtypeInvasive ductal carcinoma42 (91,5%)Other subtypes4 (8,5%)Histologic gradeGrade 12 (4,3%)Grade 218 (38,3%)Grade 323 (48,9%)Unknown4 (8,6%)cTcT221 (44,7%)cT324 (51,1%)cT4a-d2 (4,2%)cNcN018 (38,3%)cN114 (29,8%)cN26 (12,8%)cN39 (19,1%)Molecular subtypeHR+ HER2-22 (46,8%)HER2+ HR+8 (17,0%)HER2+ HR-6 (12,8%)Triple negative10 (21,3%)Breast surgeryConservative26 (55,3%)Mastectomy21 (44,7%)Axillary surgerySentinel lymph node biopsy12 (25,5%)Axillary lymph node dissection35 (74,5%)Relapse typeMetastasis7 (14,9%)Local/contralateral1 (0,83%)Deaths6 (12,8%) Citation Format: Esmeralda Garcia-Torralba, Beatriz Álvarez-Abril, Carlos Bravo-Pérez, Esther Navarro Manzano, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa García-Garre, Gema Marín Zafra, Francisco Ayala de la Peña, Elena García-Martínez. Prognostic significance of changes in tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio after neoadjuvant chemotherapy in early breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-11.

Assessment of the Prognostic Role of Ki-67 and Its Optimal Cutoff Value in Early Breast Cancer: A Retrospective Analysis

Background: Breast cancer is a heterogenous group of diseases classified into the biological subtypes luminal A, luminal B, HER2-enriched and triple negative. These subtypes have different treatment response patterns and survival rates. Ki-67 is the most commonly used proliferative marker in breast cancer and is used for the distinction between luminal A and B subtypes. Methods: A retrospective study that included patients with early breast cancer diagnosed between 2010 and 2016 and treated in a single cancer center. Results: The medical records of 498 patients were retrospectively reviewed. The median age of patients was 51 years (range: 21 – 81) and the median value of Ki-67 level among them was 20% (interquartile range: 10-30%). Ki-67 was significantly higher in younger (<35 years) and premenopausal patients (p=0.0002 and 0.0055, respectively). Higher Ki-67 level associated significantly with higher T stage, estrogen and progesterone receptors-negativity, HER2-positivity and higher grade (p=0.0256, <0.0001, <0.0001, =0.0001 and =0.0031; respectively). Univariate Cox regression analysis showed that the ≥14% and ≥20% cutoff values of Ki-67 level are associated with poorer disease-free survival (DFS) (HR=1.989 [95%CI: 1.163-3.402, p=0.0121] and HR=1.616 [95%CI: 1.001-2.61, p=0.0496], respectively). On stratifying patients according to the Ki-67 proliferation index into three strata, <14%, ≥14%--<20% and ≥20%; DFS differed significantly between them (p=0.0394). The 5-year DFS rate for the three strata was 82.2%, 64.7% and 64.8%; respectively. Conclusion: Early breast cancer patients with lower Ki-67 levels have significantly better DFS. A Ki-67 cutoff value of ≥14% appears to correlate better with DFS than the newer cutoff value of ≥20%.

Assessing 18F-FDG Uptake in the Sentinel Lymph Node in Breast Cancer.

18F-FDG PET/CT has limited value in early breast cancer. Sentinel lymph node (SLN) biopsy is the current procedure of choice to search for small metastatic deposits in the axillary lymph nodes in early breast cancer. In this retrospective study, we reevaluated 18F-FDG PET/CT images after locating the SLN on PET/CT with the help of SLN SPECT/CT images and assessed 18F-FDG uptake, particularly in the SLN. Our goal was to understand if combined evaluation of 18F-FDG PET/CT and SLN SPECT/CT could be useful for detecting early lymph node metastasis in the axilla. Methods: 18F-FDG PET/CT images of newly diagnosed breast cancer patients who also had SLN scintigraphy (SPECT/CT) and biopsy results were analyzed to assess 18F-FDG uptake in the SLN. The SLN seen on SPECT/CT images was located on PET/CT images, and its metabolic activity was assessed both visually and semiquantitatively using SUVmax 18F-FDG PET results were compared with the histopathology result for the SLN. Results: Twenty patients among 130 met the inclusion criteria. SLN SPECT/CT images were helpful for locating the SLN on 18F-FDG PET/CT images in all 20 patients. Histopathologic analysis of the SLNs demonstrated metastasis in 7 patients and no metastasis in 13. There was mild (visible) 18F-FDG uptake in the SLN (SUVmax, 1.2-4.1; metastatic deposit size, 6-8 mm) in 6 of 7 patients with SLN metastasis (85.7%). There was no or only faint 18F-FDG uptake in the SLN (SUVmax < 1) in 9 of 13 patients with no SLN metastasis (69.2%). Receiver-operating-characteristic curve analysis indicated that the SUVmax cutoff for differentiating SLN-positive from -negative cases was 0.85 (sensitivity, 85.7%; specificity, 61.5%; area under the curve, 0.747; P < 0.05). Conclusion: Combined evaluation of 18F-FDG PET/CT and SPECT/CT images to assess 18F-FDG uptake, particularly in the SLN, is a new image analysis technique to detect early metastatic disease in the axillary lymph nodes in breast cancer. Although this technique does not currently seem feasible for use in routine practice, mainly because of the limitations of current PET/CT technology in detecting small tumors, it is an interesting image analysis technique to be aware of for possible future use.

Abstract P1-01-06: Ki67-positive CTCs are associated with early disease relapse in patients with early breast cancer undergoing adjuvant chemotherapy

Abstract Background: The determination of Ki67 in the primary tumor has prognostic value in early breast cancer (BC). We evaluated Ki67 expression in circulating tumor cells (CTCs) from patients with early BC undergoing adjuvant chemotherapy and correlated Ki67 positivity with patient outcome. Methods: Ki67 expression in CTCs was evaluated by immunofluorescent analysis in paired blood samples of patients with early BC (n=166) obtained before and after adjuvant chemotherapy. Ki67 expression was also evaluated in CTC-positive patients at 6 - 24 months after the end of chemotherapy (n=31). Cytospins of peripheral blood mononuclear cells were double stained with A45-B/B3 cytokeratin and Ki67 antibodies. The proliferation index (PI) of CTCs was defined as the ratio of Ki67-positive CTCs/total CTCs. Results: CTCs were detected in 53 (32%) patients before and/or after chemotherapy. Ki67-positive [Ki67(+)] CTCs were identified in 79% of CTC-positive patients, 25% presenting exclusively Ki67(+) CTCs and 21%, exclusively Ki67(-) CTCs. The mean value of Ki67(+) CTCs/patient remained unchanged pre- and post-chemotherapy [(mean±SE): pre- vs post-chemotherapy 2.5±0.7 vs 4.2±2, respectively; p= 0.900]. Similarly, the PI among the total CTCs detected pre- and post-chemotherapy was 59% and 60%, respectively. Ten (19%) of 53 CTC-positive and 9 (8%) of 113 CTC-negative patients relapsed (p = 0.039). In addition, all CTC-positive patients who relapsed harbored Ki67(+) CTCs before and/or after chemotherapy. Interestingly, 70% of them experienced early disease recurrence, ranging from 6-29 months after the initiation of adjuvant chemotherapy. Furthermore, 38.5% of patients with exclusively Ki67(+) CTCs relapsed compared to none among patients with exclusively Ki67(-) CTCs (p = 0.041). Of the 31 CTC-positive patients evaluated during follow-up, 39% remained CTC-positive. However, only 33.3% of them harbored Ki67(+) CTCs, 8.3% had exclusively Ki67(+) CTCs and 66.7% exclusively Ki67(-) CTCs. The mean value of Ki67(+) CTCs/patient was significantly reduced on the follow-up samples [(mean±SE): follow-up vs pre-chemotherapy, 1.35±1.3 vs 2.5±0.7, respectively; p=0.014 and follow-up vs post-chemotherapy, 1.35±1.3 vs 4.2±2, respectively; p= 0.026]. Conclusions: Ki67 expression on CTCs is predictive of early relapse in patients with early BC. Ki67 expression is not decreased by adjuvant chemotherapy, whereas it is reduced early during follow-up, possibly due to adjuvant hormone therapy and/or anti-HER2 therapy. The above results suggest that additional therapy is needed for patients with early BC and Ki67(+) CTCs to prevent early disease recurrence. Citation Format: Agelaki S, Spiliotaki M, Politaki E, Spanaki A, Kassiou L, Koinis F, Georgoulias V, Mavroudis D. Ki67-positive CTCs are associated with early disease relapse in patients with early breast cancer undergoing adjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-06.

Detection of Circulating Cytokeratin-19 mRNA-Positive Cells in the Blood and the Mitotic Index of the Primary Tumor Have Independent Prognostic Value in Early Breast Cancer

BackgroundPrevious studies showed that molecular detection of CK-19 mRNA in peripheral blood and the mitotic index of primary tumors have prognostic value in early breast cancer. The aim of this study was to assess the association between these variables. Patients and MethodsThe primary tumors of 223 operable breast cancer patients (92 premenopausal and 131 postmenopausal) were evaluated for the MAI classified as either ≤ 5 per 10, 6 to 10 per 10 and > 10 per 10 or < 10 per 10 and ≥ 10 per 10 mitoses per high power field using a standardized protocol previously reported. Peripheral blood was also collected before and after the end of adjuvant chemotherapy for detection of CK-19 mRNA-positive cells using reverse transcription polymerase chain reaction previously described. ResultsAfter a median follow-up of 118 months, 75 patients (33.6%) experienced disease relapse and 56 (25.1%) died of breast cancer. MAI was strongly associated with disease-free survival (DFS) and overall survival (OS) (P < .001 for DFS and OS together). Detecting CK-19 mRNA-positive cells in the peripheral blood before but not after adjuvant chemotherapy was associated with marginally worse DFS (P = .055) and OS (P = .059). Cox regression analysis revealed that MAI and CK-19 mRNA-positive cell detection before adjuvant chemotherapy were independent variables associated with decreased DFS (P < .001 and P = .038, respectively) and OS (P < .001 and P = .029, respectively). There was no significant interaction between MAI and detection of CK-19 mRNA-positive cells. ConclusionMAI of the primary tumor and detection of CK-19 mRNA-positive cells in the blood before adjuvant chemotherapy in early breast cancer patients are 2 independent prognostic factors associated with clinical outcome.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

IntroductionOsteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis.MethodsWe measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14).ResultsPlasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels.ConclusionsThe hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study.Trial registrationNCT00002864, http://clinicaltrials.gov/show/NCT00002864

Prognostic comparison of the proliferation markers mitotic activity index, phosphohistone H3, Ki67, steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T 1-2 N 0 M 0 breast cancer

The proliferation factors: mitotic activity index (MAI), phosphohistone H3 (PPH3) and Ki67 have strong prognostic value in early breast cancer but their independent value to each other and other prognostic factors has not been evaluated. In 237 T₁₋₂N₀M₀ breast cancers without systemic adjuvant treatment, formalized MAI assessment and strictly standardized, fully automated quantitative immunohistochemistry (IHC) for Ki67, PPH3, estrogen (ER) and progesterone receptor (PR), HER2, cytokeratins-5/6 and -14, and automated digital image analysis (DIA) for measuring PPH3 and Ki67 were performed. Section thickness was measured to further control IHC measurements. All features were measured in the periphery of tumors. The different proliferation assessments and other well-established clinicopathological and biomarker prognostic factors were compared. DIA-Ki67 added prognostically to PPH3. None of the other biomarkers or clinicopathological variables added prognostically to this PPH3/Ki67 combination. However, when PPH3 is replaced by MAI the prognostic value is nearly the same. In early operable node negative breast cancer without adjuvant systemic treatment, Ki67 with a threshold of 6.5% assessed by digital image analysis in the periphery of the tumor is prognostically strong. The combination of either PPH3/Ki67 or MAI/Ki67 overshadowed the prognostic value of all other features including Ki67 alone.

P5-01-16: The Detection of Circulating CK19 mRNA-Positive Cells in the Blood and the Mitotic Index of the Primary Tumor Have Independent Prognostic Value in Early Breast Cancer.

Abstract Background: Previous studies have shown that the molecular detection of CK-19 mRNA in peripheral blood and the mitotic index of primary tumor have prognostic value in early breast cancer. The aim of the present study was to assess the association between these variables. Patients and Methods: The primary tumors of 223 operable breast cancer patients (92 premenopausal and 131 postmenopausal) were evaluated for the mitotic activity index (MAI) classified either as &amp;lt;5/10, 6–10/10 and &amp;gt;10/10 or &amp;lt;10/10 and &amp;gt;10/10 mitoses/hpf using a standardized protocol as previously reported (Baak JP et al, Breast Cancer Res Treat 2009, 115:241–254). Peripheral blood was also collected before the start and after the end of adjuvant chemotherapy for detection of CK-19 mRNA-positive cells by RT-PCR as previously described (Stathopoulou et al, Clin Cancer Res 2003, 9:5145–5151). Results: After a median follow-up of 118 months, 75 (33.6%) patients have experienced disease relapse and 56 (25.1%) have died of breast cancer. MAI was strongly associated with disease-free survival (DFS) and overall survival (OS) (p&amp;lt;0.001 for both DFS and OS). Detection of CK19 mRNA-positive cells in the peripheral blood before but not after adjuvant chemotherapy was marginally associated with worse DFS (p=0.055) and OS (p=0.059). There was no correlation between MAI and CK19 mRNA detection before chemotherapy. Cox regression analysis revealed that both MAI and CK19 mRNA-positive cell detection before adjuvant chemotherapy were independent variables associated with decreased DFS (p&amp;lt;0.001 and p=0.038, respectively) and OS (p&amp;lt;0.001 and p=0.029, respectively). The interaction test showed no significant association between MAI and detection of CK19 mRNA-positive cells. Conclusion: MAI of the primary tumor and detection CK-19 mRNA-positive cells in the blood before the start of adjuvant chemotherapy in women with early breast cancer are two independent prognostic factors associated with clinical outcome. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-16.

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

BackgroundGene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.MethodsWe included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.ResultsAn 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.ConclusionsThis study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.

A reduced qRT-PCR-based gene expression signature with prognostic value in early breast cancer.

Abstract Abstract #2030 Background: Gene profiling may improve prognostic accuracy in patients with early breast cancer, but this technology is not widely available. We used commercial assays for qRT-PCR to measure the expression of 83 genes previously found to determine breast cancer prognosis. The objective of our study was to develop a simple molecular signature predicting relapse in early breast cancer with positive hormonal receptors.&amp;#x2028; Methods: 153 patients (age 29-82 years-old) with early breast cancer and a minimum follow-up of 5 years were included. All tumours were positive for hormonal receptors and 38% had positive lymph nodes; 64% of patients received adjuvant chemotherapy (with anthracycline if N+ or high-risk N0). RNA was isolated from tissue slices of formalin-fixed paraffin-embedded samples using the MasterPure RNA Purification Kit (Epicentre Biotech). qRT-PCR amplifications were performed with TaqMan Gene Expression Assays products in an ABI PRISM 7900 HT Sequence Detection System (Applied Biosystems). The reactions were carried out using the TaqMan Low Density Arrays (Applied Biosystems). A supervised analysis was done to identify a prognostic expression signature using BRB Array Tools software. Survival curves were derived from Kaplan-Meier estimates and compared by log-rank test. The association of gene expression and clinical variables with distant metastasis-free survival (DMFS) was analyzed by Cox regression models. SAS 9.1 software package was used for statistical analyses.&amp;#x2028; Results: After a median follow-up of 92 months, 28% of patients relapsed. We defined an 8-gene prognostic signature. The distant metastasis-free survival at 5 years was calculated for this profile. DMFS was 97% -good risk- versus 60% -poor risk, HR 20.3 (95% CI 6.17-67.2), p&amp;lt;0.001. This gene expression profile was highly informative in identifying patients with distant metastasis, even when corrected for traditional prognostic factors in Cox multivariate analysis (HR 20, 95% CI 5.9-67.4). Performance was similar to that of three validated gene profiles. The validity of this signature was verified in an independent cohort obtained at the GEO database.&amp;#x2028; Conclusions: This study identifies a new molecular signature with prognostic utility that outperforms traditional histopathologic prognostic factors. Our 8-gene qRT-PCR assay is suitable for analyzing routine formalin-fixed paraffin-embedded samples in the clinical setting. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2030.

Adjuvant docetaxel combo of value in early breast cancer

Adjuvant docetaxel combo of value in early breast cancer

Adjuvant docetaxel combo of value in early breast cancer

Adjuvant docetaxel combo of value in early breast cancer

PAI-1 polymorphism and expression of uPA, PAI-1 and COX-2 in breast cancer

9674 Background: The molecular components of Plasminogen Activator system, Urokinase-type Plasminogen Activator (uPA) and its inhibitor PAI-1, are involved in tumor progression and have prognostic value in early breast cancer (BC) patients. The -675 4G/5G polymorphism of the PAI-1 promoter gene is associated with different activity levels of PAI-1 in serum. Cycloxigenase-2 (COX-2) expression is associated with poor prognosis in early BC. In addition, it has been shown that COX-2 modulates uPA expression. We aimed at studying the PAI-1 polymorphism together with the immunohistochemical expression of uPA, PAI-1 and COX-2 in BC patients Methods: Blood samples from a consecutive series of 199 BC patients were collected and PAI-1 -675 4G/5G polymorphism was analyzed by PCR technique. Immunohistochemical expression of uPA, PAI-1, COX-2, HER-2/neu, and MIB-1/Ki-67 was evaluated in the tissue sample of primitive BC. A score combining intensity and percentage of cellular immunoreactivity, was used to assess the staining of uPA, PAI-1, and COX-2. uPA and PAI-1 positivity was evaluated in tumor cells and stromal fibroblasts. Results: The 4G allele was associated with regional lymph node involvement (P=.04). No statistically significant association was found between genotype and immunohistochemical expression of uPA, PAI-1 and COX-2. uPA immunostaining directly correlated with estrogen receptor expression (P=.03). Negative uPA score was associated with negative hormonal receptor expression, high tumor grade, and high MIB-1/Ki-67 expression (p<.05). PAI-1 score directly correlated with COX-2 expression (P=.02), and strong PAI-1 immunostaining was associated with moderate/strong expression of COX-2 (P=.006). Tumors with PAI-1 positive fibroblasts showed higher MIB-1/Ki-67 expression (P=.02). Moderate/strong COX-2 expression was associated with HER-2/neu overexpression (P=.02). Conclusions: These findings suggest that BC patients carrying the 4G allele of the PAI-1 promoter may have an increased probability of axillary lymph node involvement. In addition, our data support a possible interaction between Plasminogen Activator and COX-2 systems. No significant financial relationships to disclose.

Anastrozole of global value in early breast cancer?

Anastrozole of global value in early breast cancer?

Anastrozole of global value in early breast cancer?

Anastrozole of global value in early breast cancer?