bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1-03-09: Significance of FAP, SMA and CD31 Expression in the Stroma of Breast Cancer.
Authors: Tchou J , Satija C , Zhang P , Bi Y , Davuluri R , Chen H , Majumdar R , Mies C , Herlyn M , Pure E 
Published: June 2012

Abstract
Breast cancer stroma heterogeneity has been demonstrated in various gene expression profile analyses. Whether there is any association between stroma heterogeneity and the molecular phenotype of breast cancer has yet to be established. Therefore, we performed immunohistochemical analyses (IHC) to evaluate the expression of the following stromal cell markers (fibroblast activation protein (FAP), smooth muscle actin (SMA), and CD31, an endothelial cell marker) in tumor tissues from a contemporary cohort of 52 patients comprising of all four molecular subtypes (luminal A (n=25); luminal B (n=2); Her2-neu (+) (n=5); and basal (n=20)). We hypothesize that stroma heterogeneity as reflected by the proportion of stromal cells staining (+) for FAP and SMA may correlate with their molecular epithelial phenotype. Furthermore, studying the distribution of these stromal cell markers in IHC sections may evaluate their spatial relationship with tumor cells, immune cells, and tumor microvasculature which may have strategic significance within the tumor/microenvironment.

As shown in Table 1, FAP is a more robust stromal cell marker staining 85±14% of stromal cells compared to SMA which stains only 28±29% of stromal cells (p&lt;0.05). However, the distribution of FAP, SMA and microvessel density appears to be similar in all four subtypes. Multivariate analyses to correlate molecular subtype, tumor grade, tumor size, the no. of (+) nodes, and age with the% stromal cells staining (+) for FAP, SMA and CD31 yielded a significant correlation between the intensity of FAP(+) cells with tumor size, tumor grade, and the no. of positive nodes (p=0.00134, 0.0044, and 0.01141 respectively). We conclude that 1) stroma heterogeneity on IHC does not differ significantly across molecular subtypes; 2) FAP is a robust stromal cell marker; and 3) a higher FAP expression intensity on IHC may correlate with poor prognosis. Recent reports on the role of FAP in promoting tumor growth plus the abundance of FAP expression in breast cancer stroma underscore a significant role of FAP in breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-03-09.
P1-04-03: The Effect of Survivin Downregulation on Radiosensitization of Breast Cancer Cell Lines Grown under Adherent and Stem Cell Promoting Culture Conditions.
Authors: Debeb BG , Larson R , Xu W , Lacerda L , Reuben JM , Buchholz TA , Ueno NT , Woodward WA 
Published: June 2012

Abstract
Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is a bifunctional protein that has been implicated in both control of cell division and inhibition of apoptosis. Survivin has been shown to be involved in radiation resistance of various cancer types and its expression is increased by sublethal doses of irradiation in both differentiated and cancer stem cell (CSC) population. However, it is unknown whether suppression of survivin radiosensitizes the CSC population or diminishes its self renewal ability. Herein, we cloned the survivin dominant-negative mutant lacking a phosphorylation site (T34A) (Mesri et al., 2001 JCI) into the lentiviral LeGo vectors and assessed mammosphere formation and radiosensitization in MCF7, SUM149 and SUM159 cell lines grown under adherent or stem cell promoting conditions. We found an induction of survivin by western blotting in the dominant negative mutant (T34A)-transfected cell lines. Moreover, we observed a higher than two-fold increase in the Sub-G1 population as well as an increased Caspase 3 activity in the T34A-transfected SUM149 and SUM159 cells compared to control cells indicating an anti-apoptotic function of survivin. We also found that T34A-transfected cells showed a 1.5 to 2-fold decrease in the number of mammospheres compared to the control-transfected cells. Furthermore, T34A-transfected cells showed radiosensitization in adherent cells from SUM149 and SUM159 cells but no effect was observed in MCF7 cells. However, no radiosensitization was observed in stem cell promoting culture conditions with increasing doses of radiation in all tested cell lines. This indicates that the widely used standard clonogenic assays do not optimally select anti-CSC agents and that targeted therapies should be specifically tested for their activity against the CSC population. Further functional endpoint studies will be conducted to validate the in vitro findings.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-03.
P1-04-06: Ionizing Radiation Reprograms Non-Tumorigenic Cancer Cells into Cancer Stem Cells.
Authors: Chann L , Vlashi E , Lorenza DD , Dekmezian C , Pajonk F 
Published: June 2012

Abstract
Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs) able to re-grow a tumor while their progeny lack this feature. BCSCs in breast cancer have been found to be relatively resistant to radiation and several groups reported enrichment for BCSCs when breast cancers are subjected to classical anticancer treatment. Differentiation of BCSCs is thought to be unidirectional but an alternative model assumes that stemness can be obtained by clonal evolution.
In this study, we quantified the number of BCSCs surviving after radiation treatment. We compared the number of surviving BCSCs to the expected number and found an increase in BCSCs after irradiation that could not be explained by current models. We propose that radiation induces a BCSC phenotype in previously non-BCSCs and show that this transition is Notch-dependent and coincided with up-regulation of the transcription factors Oct4, Sox-2, Nanog, and Klf4.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-06.
P1-06-24: Nuclear Localization of Stat5a Predicts Response to Antiestrogen Therapy and Prognosis of Clinical Breast Cancer Outcome.
Authors: Peck AR , Witkiewicz AK , Liu C , Klimowicz AC , Stringer GA , Pequignot E , Freydin B , Yang N , Tran TH , Rosenberg AL , Hooke JA , Kovatich AJ , Shriver CD , Rimm DL , Magliocco AM , Hyslop T , Rui H 
Published: June 2012

Abstract
Nuclear-localized and tyrosine-phosphorylated Stat5 has been reported as a favorable prognostic marker and predictor of response to antiestrogen therapy in breast cancer. Phospho-Stat5 antibodies do not distinguish between phosphorylated Stat5a and the closely related Stat5b, but Stat5a is considered more critical for normal mammary development than Stat5b. The purpose of this study was to determine whether levels of nuclear-localized Stat5a protein (Nuc-Stat5a) were prognostic of clinical outcome or predictive of antiestrogen response. Stat5a was detected by traditional diaminobenzidine-chromogen immunohistochemistry (IHC) and pathologist scoring or by quantitative immunofluorescence in five archival cohorts of breast cancer. Levels of nuclear-localized Stat5a (Nuc-Stat5a) were evaluated by pathologist scoring of whole tissue sections detected by IHC or automated quantitative analysis (AQUA) of immunofluorescently-labeled tissue microarrays. Levels of Nuc-Stat5a were reduced in invasive breast cancer tissues and lymph node metastases compared to normal tissue and ductal carcinoma in situ when quantified by AQUA (Material I; n=180). Tissues from patients not treated with adjuvant therapy or treated with antiestrogen monotherapy were analyzed according to Nuc-Stat5a status for breast cancer-specific survival (CSS) and time to recurrence (TTR) using univariate and multivariate statistical models, adjusting for clinical features including tumor grade, size, lymph node and ER, PR and Her2 status. In two prognostic cohorts of node-negative breast cancer patients, low expression of Nuc-Stat5a, detected by standard IHC (Material II; n=223) or quantitative analysis (Material III; n=198), was prognostic of poor breast cancer outcome as measured by univariate and multivariate CSS (Material II/III) and TTR (Material II). CSS and TTR analysis of two independent materials of tumors from patients treated with antiestrogen monotherapy and analyzed by standard IHC (Material IV; n=73) or quantitative immunofluorescence (Material V; n=97) indicated that patients whose tumors expressed low levels of Nuc-Stat5a were at a greater than 4-fold risk of antiestrogen therapy failure when adjusted for hormone receptor status and clinical features (multivariate CSS: Material IV HR=4.3 (1.2,15.6), p=0.03; Material V HR=5.0 (1.87,13.06), p=0.001). In conclusion, loss of Nuc-Stat5a is a promising independent marker of poor breast cancer prognosis in node-negative, non-adjuvant treated breast cancer patients. Additionally, Nuc-Stat5a may be a useful clinical tool to predict tumor response to antiestrogen therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-24.
P1-07-15: The Reliability of Ki-67 Expression Assessment Using Core Needle Biopsy and Surgical Specimens of Invasive Breast Cancer: Can Ki-67 Change Predict Benefits of Preoperative Endocrine Therapy?
Authors: Mizuno Y , Takayanagi H , Sato K 
Published: June 2012

Abstract
Background: The use of Ki-67 change as a predictive marker in breast cancer has been widely investigated in patients treated with preoperative endocrine therapy. It has been assumed that Ki-67 expression determined using core needle biopsy and surgical specimens of invasive breast cancer is concordant. Many studies have suggested the concordance of the results obtained using core needle biopsy and surgical specimens for expression of the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type2 (HER2) status in early-stage breast cancer. However, there was few study to compare Ki-67 expression in the core needle biopsy and surgical specimens. We conducted a retrospective study of Ki-67 expression assessment between the two types of specimens to answer this question.
Methods: A total of 269 patients underwent primary operations for early-stage breast cancer at Tokyo-West Tokushukai Hospital from August 2008 to May 2011. Among these patients, 169 patients who received core needle biopsy prior to operation were enrolled.
Patients with ductal carcinoma in situ and those with neoadjuvant chemotherapy were excluded. A cutoff value of 20% was used for Ki-67-positive criteria. We also examined ER, PgR, and HER2 expression and compared it with Ki-67 expression. Statistical significance for concordance rates between the two types of specimens was evaluated by Wilcoxon t-test. To evaluate the consequence of formalin and genetic heterogeneity, parameters such as operative method and tumor size were analyzed by χ2 analysis.
Results: The concordance rate between the two types of specimens for Ki-67 expression was 76%, and this was significantly lower than that for ER expression, which was 96%. The concordance rates for PgR and HER2 expression were 88% and 91%, respectively, and they were not significantly different from the rate for Ki-67 expression. 45 patients(34.6%) had received mastectomy in the Ki-67 concordant group, and 14 patients(34.1%) in the discordant group. 55 patients(42.0%) showed T2∼ tumor size in the concordant group, 13 patients(31.7%) in the discordant group. No significant differences of parameters such as operative method (mastectomy vs breast conserving surgery) and tumor size (T1 vs T2∼) were observed between the two patient groups.
Conclusion: The reliability of Ki-67 concordance rate assessment using core needle biopsy specimens was significantly lower than that of ER expression. A standard pathological assessment of Ki-67 expression might be needed for the possible use of Ki-67 as a predictive marker for preoperative endocrine therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-15.
P1-08-05: Age and Survival in Women with Early Stage Breast Cancer: An Analysis Controlling for Tumor Subtype.
Authors: Partridge AH , Hughes ME , Ottesen R , Wong Y-N , Edge SB , Theriault RL , Blayney DW , Niland JC , Winer EP , Weeks JC , Tamimi RM 
Published: June 2012

Abstract
Background: Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death in women with early stage breast cancer. However, young women are more likely to have aggressive subtypes of breast cancer. No prior studies have adequately controlled for tumor phenotype, including HER-2/neu (HER2) status, in particular. Recent evidence has suggested that the prognostic effect of young age varies by tumor subtype.
Methods: We examined data from women with newly diagnosed Stage 1–3 breast cancer presenting to one of 8 NCCN centers between January 2000 and December 2007. Multivariate Cox proportional hazards models were used to assess the relationship between age and breast cancer specific survival, controlling for known prognostic factors and treatment. In addition, we conducted stratified analyses by estrogen receptor (ER) and HER2 status.
Results: 19,633 women with Stage 1–3 breast cancer eligible for analysis including 2,177 (11%) who were age 40 years or younger at diagnosis. Younger women were more likely to be non-white or Hispanic, more educated, employed, and to have higher stage, high grade, ER-negative, progesterone receptor (PR) negative, and HER2−positive disease, and treated with chemotherapy and trastuzumab (all variables P&lt; 0.0001 by Chi-Square test). 5-year survival among younger women was 94.1 (95% Confidence Interval [CI] 92.9−95.3) and 96.3 (95% CI 95.9−96.6) for older women. In a multivariate Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women age &lt; 40 or younger at diagnosis had increased mortality compared to older women (Hazard Ratio [HR] 1.26, 95% CI 1.02−1.56). In stratified analyses, age 40 or less was associated with increased mortality among women with ER-positive disease (HR 1.44, 95% CI 1.01−2.05), but was not among those with ER-negative disease (HR 1.15, 95% CI 0.85−1.55). Younger age was associated with a statistically significant increase in mortality among women with HER2−negative disease (HR 1.29, 95% CI 1.00−1.68), but this difference did not reach statistical significance among those with HER2−positive disease (HR 1.30, 95% CI 0.82−2.09). Conclusions: The effect of age on short-term survival of women with early breast cancer appears to vary by breast cancer subtype, particularly ER status. Further research to elucidate differences in breast cancer biology and efficacy of therapy within tumor types by age is warranted.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-05.
P1-08-11: Differences in Recurrence Dynamics between Lobular and Ductal Invasive Breast Cancer.
Authors: Siesling S , Kwast ABG , Grandjean I , Ho V , van der Sangen MJC , Menke-Pluymers MBE , Tjan-Heijnen VCG 
Published: June 2012

Abstract
Introduction: Many studies investigated disease free survival after breast cancer treatment. A few studies focused on patterns of recurrence risk over time. However, they ignored the impact of histology. This study aimed to determine differences in recurrence dynamics on population-based data between patients with a ductal breast cancer (DBC) and lobular breast cancer (LBC).
Methods: All surgically treated women diagnosed in 2003–2004 with invasive DBC or LBC, with no distant metastases or second primary breast cancer were selected from the Netherlands Cancer Registry. The recurrence patterns were studied using the life-table method to estimate the hazard rate for the first recurrence with the worst prognosis (locoregional (LRR) or distant metastases), that is, the conditional probability of manifesting recurrence in a time interval, given that the patient is clinically free of any recurrence at the beginning of the interval. The wilcoxon test was used to determine differences in recurrence patterns between DBC and LBC.
Results: Of 16,231 women identified, 87% had DBC and 13% LBC. LRR was found in 4% of the DBC and in 3% of the LBC patients, whereas metastases were found in 11% and 10% of patients, respectively. Notably, in DBC patients a peak in recurrence rate was seen between 1–2 years after diagnosis, both for LRR and distant metastases. On the other hand, in LBC patients the recurrence pattern did not show major peaks: after 2 years the curve revealed an almost steady level for LRR and distant metastases. This recurrence pattern was significantly different (P=&lt;0.001). Moreover, the influence of age, stage and treatment on recurrence differed between DBC and LBC. We also noticed a difference in localization of metastasis.
Conclusion: Our study showed an overall equal number of recurrences after DBC and LBC, but with a totally different recurrence pattern, which could have implications on follow-up of the patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-11.
P1-08-16: Benign Breast Disease (BBD) and Breast Cancer in African American Women.
Authors: Fehmi RA , Cote M , Ruterbusch J , Alosh B , Bandyopadhyay S , Albashiti B , Frost MH , Hartmann LC , Visscher DW 
Published: June 2012

Abstract
African American (AA) women have higher mortality rates from breast cancer (BrCa) and are diagnosed at younger ages than their Caucasian counterparts. Women who have had a benign breast biopsy are at increased risk of the disease, although less is known about the risk of BrCa associated with benign breast disease in AA women. We examined 1428 breast biopsies from AA women which occurred from 1997–2000 and assessed various pathologic markers including: apocrine metaplasia, ductal hyperplasia including atypia, evidence of cysts, duct ectasia, fibrosis, intra-ductal papilloma, sclerosing adenosis, columnar alteration, and involution (atrophy). These women were followed for later BrCa through the Metropolitan Detroit Cancer Surveillance System, part of the Surveillance, Epidemiology and End Results (SEER) program through 2008. Women who developed BrCa were compared to those in the cohort who did not, and to other AA women with BrCa in the SEER registry. AA women in our study were also compared to Caucasian women in the Mayo Clinic cohort. Differences in variables were assessed by chi-squared tests and 95% confidence intervals. Of the 1428 biopsies, 52 (3.6%) subsequent incident breast cancers were reported in SEER. The mean age at diagnosis was 59, and the mean time from biopsy to BrCa diagnosis was 6.1 years. Individuals with atypical ductal hyperplasia at biopsy (n=37, 2.6%) were more likely to develop breast cancer (n=7, 13.5%, p&lt;0.01). No other pathologic variables were associated with increased risk. Women in our cohort with breast cancer did not differ from AA in the SEER database with respect to age at diagnosis, stage at diagnosis, or receptor positivity. Compared to the Caucasian women in the Mayo Clinic BBD cohort, AA women in our study were younger at biopsy (p&lt;0.01), but had similar percentages of involution and atypia (p=0.50 and 0.15, respectively). Our preliminary findings among a relatively small group of AA women with prior benign breast biopsies and incident breast cancers suggest that results from the Mayo Cohort study are likely to apply to AA populations.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-16.
P1-08-20: Parity Interferes with the Effect of Age at Diagnosis on the Frequency Breast Cancers Are Triple-Negative.
Authors: Vannevel V , Brouckaert O , Leunen K , Amant F , Berteloot P , Dieudonne A-S , Laenen A , Wildiers H , Paridaens R , Van Limbergen E , Weltens C , Moerman P , Smeets A , Lambrechts D , Christiaens M-R , Vergote I , Neven P 
Published: June 2012

Abstract
Background Epidemiologic studies show an age related decrease in the frequency that breast cancers are triple negative (TN) (estrogen receptor, progesterone receptor and HER-2 negative). Parity increases the risk of TN breast cancer as a previous full-term pregnancy mainly protects against ER+ breast cancer. It is unknown whether this protective affect appears at all ages of breast cancer diagnosis. We study the frequency of triple negative breast cancers by parity and age at breast cancer diagnosis.
Methods We performed a retrospective case-case analysis including 1583 consecutive female patients with primary diagnosis of invasive breast cancer, &lt; 51 years at diagnosis. We compared the frequency of TN tumors between parous (N = 1271) and nulliparous (N = 312) women in three age categories (21 to 30 yrs, 31 to 40 yrs and 41 to 50 yrs). For statistical analysis we used a logistic regression model.
Results We confirmed a decrease of TN breast cancer with age (p &lt; 0.0001). This decrease is stronger pronounced in the nulliparous group. Parity favors TN tumors only in women &gt; 40 years at breast cancer diagnosis.

Discussion: Although several other factors may affect the frequency breast cancers are TN, age at breast cancer diagnosis interacts with the effect of a previous pregnancy on the frequency breast cancers are TN. Breast cancers in young women (&lt; age 40) may have been initiated long before pregnancy can induce a protective effect against ER-positive cases. The international BCAC has recently accepted to validate our UZ Leuven findings.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-20.