bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-07-07: Circulating Tumor Cells Predict Survival in Non-Metastatic Breast Cancer.
Authors: Lucci A , Krishnamurthy S , Bhattacharyya A , Lodhi A , Hall C , Singh B , Anderson A , Bedrosian I , Kuerer H 
Published: June 2012

Abstract
Background: Circulating tumor cells (CTCs) predict outcome in metastatic breast cancer (BC), but their prognostic significance in non-metastatic BC is unclear. This study determined whether CTCs could be identified in non-metastatic BC patients and 2) if CTCs predict relapse-free and overall survival.
Methods: Clinical stage I-III BC patients seen at a single tertiary cancer center provided informed consent to participate in an IRB-approved study involving collection of blood (7.5 ml x 2 tubes) before systemic therapy and at the time of surgery for their primary BC. CTCs were detected using the Cell SearchTM system. A positive result was defined as the presence of two or more cells per 7.5 ml blood since a threshold for positivity has not been established in primary BC. Statistical analyses were done using STATA-IC 11 software.
Results: We prospectively evaluated 291 patients. Mean age was 54 years, and median follow-up was 30 months. 54% (157) had T1 tumors, 36%(104) T2, 6% (18) T3, and 4%(12) had T4 disease; 37% (107/289) were clinically node-positive (LNs) by axillary ultrasound and FNA. Two or more CTCs were identified in 10% (29) patients. Seventy-seven percent (225) patients were hormone receptor positive, 11% (32) were HER2 positive while 16% (48) expressed no receptors. Sixteen percent (48) were tumor grade 1, 50% (143) were grade 2 and 34% (98) were grade 3. Systemic chemotherapy and/or endocrine therapy were administered in 80% (233/289) of patients. Sixty-eight percent (167/244) of patients were post-menopausal. Additionally, there was no significant correlation between CTCs with primary tumor size, lymph node status, estrogen or progesterone receptor status, HER2 amplification or tumor grade. Thirty-eight percent (6/16) of all relapses occurred in patients with 2 or more CTCs (HR: 4.48 (95% C.I. 1.61−12.45), Logrank P 0.002) while 40% (4/10) of all deaths occurred in patients with 2 or more CTCs (HR: 4.54 (95% C.I. 1.27−16.25), Logrank P 0.011).
Conclusions: CTCs were a significant predictor of disease-free and overall survival in non-metastatic breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-07.
P4-07-18: Prospective Assessment of Circulating Tumor Cells and Serum Markers for PFS Prediction in Metastatic Breast Cancer.
Authors: Bidard F-C , Hajage D , Bachelot T , Delaloge S , Brain E , Campone M , Cottu P , Beuzeboc P , Mathiot C , Pierga J-Y 
Published: June 2012

Abstract
Purpose: Circulating tumors cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum markers levels are also used for the same purpose, and no clear comparison as been reported to date.
Patients and methods: The IC 2006–04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and Overall survival (OS). A pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (CEA, CA 15–3, CYFRA 21.1), and of serum non-tumor markers (LDH, ALP) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes.
Results:
Table 1 shows the incidence of each of the 6 blood markers. Assessing all the 6 markers retrieved 90% of patients with at least one elevated marker at baseline. Interestingly, a combination of two markers (CA 15–3 and CYFRA 21.1, often used in lung cancer) retrieved 86% of patients with at least one marker elevated at baseline.
All 6 markers were correlated with poor performance status, high number of metastatic sites and with each other. Each marker was associated, when elevated at baseline, with a significantly shorter PFS in univariate anlaysis.
Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and week 6–9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction.
Conclusion: In the largest prospective CTC study in metastatic breast breast cancer, we previously reported that CTC count, but not serum markers, is an independent prognostic factor for PFS and overall survival. However, for the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15–3, CYFRA 21.1 is commonly elevated in metastatic breast cancer and has a strong prognostic value.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-18.
P4-08-05: Diagnostic Significance of Exosomal miRNAs in the Plasma of Breast Cancer Patients.
Authors: Kwong A , Ng EKO , Leung CPH , Chan V , Li R , Wong CLP , Ma ESK 
Published: June 2012

Abstract
Background and Aims: Emerging evidence that microRNAs (miRNAs) play an important role in cancer development has opened up new opportunities for cancer diagnosis. Recent studies demonstrated that released exosomes which contain a subset of both cellular mRNA and miRNA could be a useful source of biomarkers for cancer detection. Here, we aim to develop a novel biomarker for breast cancer diagnosis using exosomal miRNAs in plasma. Methods: We have developed a rapid and novel isolation protocol to enrich tumor-associated exosomes from plasma samples by capturing tumor specific surface markers containing exosomes. After enrichment, we performed miRNA profiling on four sample sets; (1) Ep-CAM marker enriched plasma exosomes of breast cancer patients; (2) breast tumors of the same patients; (3) adjacent non-cancerous tissues of the same patients; (4) Ep-CAM marker enriched plasma exosomes of normal control subjects. Profiling is performed using PCR-based array with human microRNA panels that contain more than 700 miRNAs.
Results: Our profiling data showed that 15 miRNAs are concordantly up-regulated and 13 miRNAs are concordantly down-regulated in both plasma exosomes and corresponding tumors. These account for ∼25% (up-regulation) and ∼15% (down-regulation) of all miRNAs detectable in plasma exosomes. Our findings demonstrate that miRNA profile in EpCAM-enriched plasma exosomes from breast cancer patients exhibit certain similar pattern to that in the corresponding tumors. Based on our profiling results, plasma signatures that differentiated breast cancer from control are generated and some of the well-known breast cancer related miRNAs such as miR-10b, miR-21, miR-155 and miR-145 are included in our panel list. The putative miRNA biomarkers are validated on plasma samples from an independent cohort from more than 100 cancer patients. Further validation of the selected markers is likely to offer an accurate, noninvasive and specific diagnostic assay for breast cancer.
Conclusions: These results suggest that exosomal miRNAs in plasma may be a novel biomarker for breast cancer diagnosis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-05.
P4-09-06: The Prognostic Value of Tumour-Stroma Ratio in Triple Negative Breast Cancer.
Authors: Moorman AM , Vink R , Heijmans HJ , van der Palen J , Kouwenhoven EA 
Published: June 2012

Abstract
Background: Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with good and poor outcome. Recent studies suggested an important role for stroma in tumour growth and progression. In colorectal-, oesophageal- and breast cancer, the tumour-stroma ratio was found to be of prognostic value.
Objective: to evaluate the prognostic value of the tumour-stroma ratio in triple-negative breast cancer.
Methods: During the period January 2004–2008, 124 consecutive triple negative breast cancer patients treated in our hospital were retrospective evaluated. Routine Haematoxylin-Eosin (H&E) stained histological sections were evaluated by two investigators (kappa 0.735) for stroma percentage, growth pattern (pushing margin), necrosis and amount of lymphocytic infiltrate. Patients with less than 50% stroma were classified as stroma-low and patients with ≥ 50% stroma were classified as stroma-high.
Results: of 124 triple-negative breast cancer patients, 50 (40%) had a stroma-high and 74 (60%) had a stroma-low tumour. Survival analysis revealed a 5 years relapse free period (RFP) of 85% in the stroma-low and 45% in the stroma-high group. Overall survival (OS) was 89% for stroma-low and 65% in the patients with a stroma-high tumour. Both RFP and OS were significantly worse in patients with stroma-high tumours compared to stroma-low. In a multivariate cox-regression analysis, tumour stroma remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07−5.29; p=0.033) and OS (HR 3.00; 95% CI 1.08−8.32; 0.034) when corrected for other clinical-pathological variables. In addition, tumour-stroma proved to be a strong prognostic variable when compared to nodal status, tumour grade and tumour size, with respectively a HR of 2.39 (95% CI 1.37−6.26) versus HR 2.18 (95% CI 1.06−4.48), HR 2.10 (95% CI 0.89−4.91) and HR 0.53 (95% CI 0.70−3.91) for RFP with comparable numbers for OS. Conclusion: Tumour-stroma ratio is a strong independent prognostic variable in triple-negative breast cancer. It is easy to determine, reproducible (kappa 0.735) and can be easily incorporated into routine histological examination. This parameter optimizes risk stratification and could be target for future therapies.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-06.
P4-09-26: Prognostic Significance of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) in Breast Cancer.
Authors: Dechaphunkul A , Phukaoloun M , Kanjanapradit K , Graham K , Ghosh S , Santos C , Mackey JR 
Published: June 2012

Abstract
Background: Despite advances of systemic treatment in breast cancer guided by hormonal status and HER2 amplification, new prognostic and predictive factors are still warranted to optimize treatments among these patients. Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), a physiologic inhibitor of Matrix Metalloproteinases (MMPs), can act in both pro- and anti-tumoral effects. The prognostic significance of TIMP-1 in breast cancer is still controversial. This study aims to determine the prognostic significance of TIMP-1 in breast cancer. Material and Methods: One-hundred and seventy-six primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1. Immunohistochemical analysis was independently reviewed by two pathologists.
Results: At the optimized cut-off point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.6 (p = 0.039), but without significant differences in overall survival (HR 1.29, p = 0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.2, p = 0.35), high expression was associated with shorter overall survival (HR 1.73, p = 0.027). In multivariate analysis, when considering stage, histologic grade, hormonal and HER2 status, TIMP-1 RNA levels remained independently prognostic for early relapse (HR 1.68, p = 0.04).
Discussion: Elevated TIMP-1 RNA levels are independently prognostic for early recurrence, whereas protein overexpression of TIMP-1 is correlated with short overall survival in primary breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-26.
P4-10-02: A Meta-Analysis of the Association of Blood Levels of Vitamin-D and the Risk of Breast Cancer.
Authors: Amir E , Carlsson L , Seruga B , Ocana A , Goodwin PJ 
Published: June 2012

Abstract
Background: A considerable body of literature has examined the association of vitamin-D with breast cancer risk and the potential role in its prevention. Geographic studies show higher incidence of breast cancer in patients residing at high latitudes. Other data linking vitamin-D deficiency to breast cancer risk are inconsistent.
Materials and Methods: A literature based meta-analysis was conducted. Odds ratios (OR) for breast cancer based on blood levels of 25-hydroxy or 1,25-hydroxy vitamin-D were computed and pooled. Analysis was conducted separately for studies where blood levels were taken before (group A) or after (group B) breast cancer diagnosis.
Results: Thirteen studies were identified. Nine studies were included in group A and 4 studies included in group B. For group A, there was no significant association between lower vitamin-D levels and breast cancer risk (pooled OR = 1.09, 95% confidence intervals 0.99−1.20, p=0.08). For group B, there was a highly significant association between lower vitamin-D levels and breast cancer (pooled OR = 2.81, 95% confidence intervals 1.70−4.65, p&lt;0.001). The test for interaction between groups was highly significant (p&lt;0.001). When all studies were pooled, the OR was 1.38 (95% confidence intervals 1.13−1.70, p=0.002).
Conclusion: When measured before breast cancer diagnosis, blood levels of vitamin-D are not associated with breast cancer risk. Breast tumors have been shown to differentially express vitamin-D hydroxylase. Therefore, any association of vitamin-D and breast cancer in studies measuring blood levels after breast cancer diagnosis may be confounded by reverse causation bias.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-02.
P4-10-08: Risk Factor Profiles of Women with DCIS and Invasive Ductal Breast Cancers.
Authors: Schnabel F , Chun Kim J , Billig J , Cimeno A , Mehta P , Guth A , Hochman T , Shapiro R , Hiotis K , Siegel B , Axelrod D 
Published: June 2012

Abstract
Background There are well established risk factors for breast cancer, including elements of personal and family history. Ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) have long been viewed as representing two points on the spectrum of one disease. There is limited and conflicting information in the literature regarding risk factor profiles for DCIS as compared with IDC. The purpose of this study was to investigate the relationship of established risk factors in a population of women newly diagnosed with pure DCIS and IDC. Methods
The Breast Cancer Database at NYU Langone Medical Center was queried for women who were diagnosed with pure DCIS and IDC from 1/2010-3/2011. Variables of interest included: age, family history of breast cancer (FHBC), BRCA1/2 status, age at menarche and menopause, parity, age at first birth, breast feeding, body mass index (BMI), history of atypical hyperplasia or lobular carcinoma in situ (ADH, ALH, LCIS), stage, ER/PR status, and method of presentation. Wilcoxon non-parametric tests, Chi-Square tests, and Fisher's Exact Tests were used to evaluate differences among DCIS and IDC patients.
Results Of the 593 women identified in this study, 140 (24%) had pure DCIS and 453 (76%) had IDC. The median age at diagnosis was 59 years. There were 9 (1.5%) BRCA1/2 mutation carriers. Of these, 7 had IDC and 2 had DCIS. The majority of patients with IDC were stage I (67%) and ER/PR+ (73%). The majority of patients with DCIS were also ER/PR+ (71%). In our cohort, the majority of DCIS (83%) was mammographically detected versus 47% of IDC cases. There were no statistically significant differences in breast cancer risk factors between the two groups.

Conclusions In contrast to some previously published work, the risk factor profile in our cohort was similar for patients with IDC and DCIS. In this population, the majority of cases of DCIS were detected mammographically, underscoring the importance of mammography in early detection of breast cancer. There is increasing interest in identifying a population of women with DCIS who might never progress to invasive disease. Our data suggests that this population is unlikely to be distinguished by its risk factor profile. Genetic and molecular characteristics are more likely to provide the criteria by which this subgroup of patients is identified.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-08.
P4-11-14: Number Needed To Treat (NNT) as a Measure of Incremental Drug Benefit: Denosumab vs. Zoledronic Acid for the Prevention of Skeletal Related Events (SREs) in Advanced Breast Cancer.
Authors: Dranitsaris G , Kaura S 
Published: June 2012

Abstract
Background
Intravenous zoledronic acid (ZOL) is the standard of care for the prevention of SREs in advanced breast cancer. However, monthly subcutaneous denosumab (Dmab) was recently approved in the US, as an alternative to ZOL based on the results of a large randomized trial which demonstrated a prolongation in median time to first SRE (HR = 0.82, p = 0.01) and a 5.8% (p = 0.01) absolute reduction in SREs in favour of Dmab over the 34 month study period. The challenge for clinicians and payers is how to reconcile the modest benefits of Dmab with the cost, which is approximately twice that of ZOL. NNT represents the number of patients that need to be treated with a new intervention in order to avoid one additional event, and is a widely accepted approach used to make sense of numerical results from clinical trials. In this analysis, the NNT approach was used to assess the incremental benefit of Dmab over ZOL for the prevention of SREs in advanced breast cancer.
Methods: The pivotal randomized trial for Dmab vs. ZOL in breast cancer (Stopeck, JCO 2010 & US PI 2010) was reviewed. As an alternative to ZOL, the NNT with Dmab to avoid any SRE at 12 and 34 months (trial end) was determined. NNT by type of SRE was also estimated. These consisted of pathologic fractures, radiation to bone, spinal cord compressions and surgery to bone. The calculated NNT represents the incremental benefit provided by Dmab above and beyond Zometa therapy.
Results: To avoid a single SRE after 12 months of treatment of continuous therapy with Dmab, approximately 36 patients need to be treated. To avoid a single fracture and radiation to bone, approximately 39 and 27 patients need to be treated with Dmab over a 34 month period. Dmab was unable to offer any incremental benefit over ZOL in terms of avoiding spinal cord compressions or surgery to bone after 34 months of treatment.
Discussion: The NNT approach is a simple and effective method to express the findings in a clinically meaningful way. In this analysis, the incremental benefit of Dmab would only be realized when a minimum of 36 patients are treated for 12 months. For the more severe skeletal-related events, in terms of clinical and economic burden to patients and society, such as spinal cord compression and surgery to bone, Dmab did not offer any incremental benefit over ZOL in terms of SRE avoidance. This marginal incremental benefit needs to be considered alongside the high cost of Dmab.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-14.
P4-11-18: Mammographic Surveillance in Atypical Hyperplasia of the Breast and Subsequent Development of Cancer. A Need for Long Term Follow Up.
Authors: Koron R , Sridharan U , Mitchell G , Holcombe C 
Published: June 2012

Abstract
Introduction Atypical hyperplasia of the breast is a known risk factor for breast cancer. Despite this risk there are no published guidelines on a recommended follow up regime for these patients.
Methods A retrospective study was carried out on 1920 core biopsy results within a major screening breast unit from 2001 to 2005. Patients who had a final diagnosis of Atypical Ductal Hyperplasia (ADH), Atypical Lobular Hyperplasia (ALH) and Lobular Carcinoma in Situ (LCIS) were included.
Information was extracted from multidisciplinary team meeting records, departmental data bases, pathology and radiology reports. Details of follow up and subsequent cancer diagnosis were noted.
Results 83 patients were diagnosed with ALH, ADH or LCIS from a core biopsy. The mean age was 54 years (range 40–85 years). Seventy six (91.6%) of these patients went on to have an excision biopsy. Sixty four (77.1%) women have received long term mammographic follow up ranging from 5 to 9 years to date. Nineteen patients did not receive mammographic surveillance. Of this group 2 patients with LCIS had bilateral risk reducing mastectomies and 2 patients died shortly after diagnosis with no evidence of breast cancer. Eight patients developed breast cancer 3 to 8 years after their initial diagnosis. Of these, four patients developed cancer in the same breast that atypia had been diagnosed in previously, and four in the contra lateral breast.
Conclusion 12.5 % of patients in the follow up group developed breast cancer within 8 years of diagnosis of atypical hyperplasia. A review of the literature suggests that in view of the increased risk of subsequent breast cancer in this group of women long term follow up is required. On the basis of these findings we recommend that all patients diagnosed with ALH, ADH or LCIS should be entered into an 18 monthly mammogram surveillance programme for 15 years.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-18.
P4-11-22: Familial History of Cancer among Breast Cancer Women under 36 yr. in Rio De Janeiro, Brazil.
Authors: Koifman S , Ortega GPJ , Koifman RJ 
Published: June 2012

Abstract
Background. Antecedents of familial history of cancer (FHC) have been reported as an important feature observed among young women with breast cancer (BC).
Objective. To explore the distribution of FHC in a sample of young women with BC in Brazil.
Methods. Antecedents of FHC were obtained by a face to face interview carried out with 224 BC cases 20–35 yr., and 246 age-frequency matched controls, enrolled in a hospital-based case control study carried out along 1996–2006 in Rio de Janeiro, Brazil. Unconditional logistic regression was performed and BC odds ratios adjusted for age and education (adj. OR) were obtained according to FHC characteristics (parenthood degree, age of diagnosis and amount of relatives with cancer).
Results. BC antecedents among 1 st degree relatives was 5.4% among BC cases and 1.2% of controls (p=0.01). The adj. OR for BC among 1st degree relatives was 4.3, 95% CI 1.2−15.8. Comparatively to families without BC antecedents, an adj. OR =2.4, 95% CI 1.4−4.1 was observed for those with 1 reported BC case, and an adj. OR = 3.7, 95% CI 1.0–14.0 for those with 2 or more BC cases (p trend =0.0002). A similar trend was verified according to all other cancer sites (p-trend &lt; 0.0001). The reported median age of BC diagnosis in the 1st generation (proband grand-mothers) was 76 yr., being 45 yr. at the 2nd generation (proband mothers), and 38,4 yr. at the 3rd (proband sisters). A similar trend along generations was also verified for other cancer sites among case relatives, respectively, 69 yr., 58 yr. ***, and 45 yr. The mean age of diagnosis among the cases offspring was 6.7 yr. (standard deviation, SD = 0.6) and 12.0 yr. (SD = 1.4) among the controls descents (p&lt; 0.01). Brain cancer reported among case relatives was 6.0 fold higher than among control relatives (3.7 fold higher for ovarian cancer, and 3.2 higher for skin cancer).
Discussion. The observed results reveal that cancer risks among relatives of young women with BC are either higher for BC or other selected cancer sites. The observed decline along successive generations on the age at diagnosis of BC and other tumors is suggestive of recent genetic-environmental interaction in the studied sample of young women with BC in Brazil.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-22.