bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-07-26: Prognostic significance of the maximal value of the baseline standardized uptake value on fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for predicting pathologic malignancy of operable breast cancer with neoadjuvant chemotherapy
Authors: Kadoya T , Akimoto E , Emi A , Shigematsu H , Masumoto N , Okada M 
Published: August 2014

Abstract
PURPOSE: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is potentially useful in predicting pathological complete response (pCR), disease free survival (DFS) and overall survival (OS) of breast cancer patients with neoadjuvant chemotherapy.
MATERIALS AND METHODS: 77 breast cancer patients (mean age ± SD: 52.6 ± 11.2 years) with clinical Stage I∼III between January 2006 and December 2011, were prospectively evaluated (median follow up period:26.5 months). Neoadjuvant chemotherapy of an anthracycline-based regimen and taxane was performed, and patients underwent a whole-body FDG PET/CT before and after chemotherapy. The maximal value of the baseline standardized uptake values (SUVmax) were assessed for predicting pCR, DFS and OS. For the evaluation of relationship between SUVmax values and prognosticators such as hormone receptors, human epidermal growth factor receptor 2 (HER2), nuclear grade, lymph node metastasis and tumor size, statistical analyses were performed using Student t test and log-rank test, and p values of less than 0.05 were considered to indicate statistically significant differences.
RESULTS: Clinical Stage included were I (n = 2, 2.6%), II (n = 62, 80.5%) and III (n = 12, 15.6%). Tumors with estrogen receptor positive were 52 (67.5%) and negative were 24 (31.2%). Therapeutic response by neoadjuvant chemotherapy was obtained in 15 patients (19.5%) with pCR and 60 (77.9%) without pCR. Patients were divided into two groups according to cut-off SUVmax established on the basis of receiver operating characteristic (ROC) analysis (&lt;6.0 vs. ≥6.0, AUC=0.721). When related to the biologic parameters, estrogen receptor (OR:3.75, 95%Cl:1.36–10.35, p = 0.02), but not progesterone receptor (OR:2.31, 95%Cl:0.89–6.00, p = 0.08) nor HER2 status (OR:1.51, 95%Cl:0.47–4.85, p = 0.70) were found strong relation to SUVmax values.

There was a significant difference in OS between two groups (p = 0.05), but, pCR (OR:1.07, 95%Cl:0.34–3.40, p = 0.86) and DFS (p = 0.07) did not show strong relationship with SUVmax values.

CONCLUSION: SUVmax on FDG PET/CT before neoadjuvant chemotherapy have a predictive value for high-grade malignancy and prognosis in clinical Stage I∼III breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-26.
Abstract P6-07-27: Body mass index and survival after breast cancer diagnosis in Japanese women
Authors: Kawai M , Minami Y , Nishino Y , Ohuchi N , Kakugawa Y 
Published: August 2014

Abstract
Background: Body mass index (BMI) may be an important factor affecting breast cancer outcome. Studies conducted mainly in Western countries have reported a relationship between higher BMI and a higher risk of all-cause death or breast cancer-specific death among women with breast cancer, but only a few studies have been reported in Japan so far. In the present prospective study, we investigated the associations between BMI and the risk of all-cause and breast cancer-specific death among breast cancer patients overall and by menopausal status and hormone receptor status.
Methods: The study included 653 breast cancer patients admitted to a single hospital in Japan, between 1997 and 2005. BMI was assessed using a self-administered questionnaire. The patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to quartile points of BMI categories, respectively: &lt;21.2, ≥21.2 to &lt;23.3 (reference), ≥23.3 to &lt;25.8 and ≥25.8 kg/m2.
Results: During the follow-up period, 136 all-cause and 108 breast cancer-specific deaths were observed. After adjustment for clinical and confounding factors, higher BMI was associated with an increased risk of all-cause death (HR = 2.61; 95% CI: 1.01–6.78 for BMI ≥25.8 vs. ≥21.2 to &lt;23.3 kg/m2) among premenopausal patients. According to hormonal receptor status, BMI ≥25.8 kg/m2 was associated with breast cancer-specific death (HR = 4.95; 95% CI: 1.05–23.35) and BMI &lt;21.2 kg/m2 was associated with all-cause (HR = 2.91; 95% CI: 1.09–7.77) and breast cancer-specific death (HR = 7.23; 95% CI: 1.57–33.34) among patients with ER+ or PgR+ tumors. Analysis by hormonal receptor status also showed a positive association between BMI and mortality risk among patients with ER+ or PgR+ tumors and with BMI ≥21.2 kg/m2 (p for trend: 0.02 and 0.031 for all-cause and breast cancer-specific death, respectively).

Conclusions: Our results suggest that both higher BMI and lower BMI are associated with an increased risk of mortality, especially among premenopausal patients or among patients with hormonal receptor positive tumors. Breast cancer patients should be informed of the potential importance of maintaining an appropriate body weight after they have been diagnosed.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-27.
Abstract P6-08-01: Perceptions of breast cancer risk, psychological adjustment and behaviors in adolescent girls at high-risk and population-risk for breast cancer
Authors: Bradbury AR , Patrick-Miller L , Egleston B , Schwartz L , Tuchman L , Moore C , Rauch P , Sands C , Shorter R , Rowan B , Malhotra S , van Decker S , Schmidheiser H , Sicilia P , Bealin L , Daly M 
Published: August 2014

Abstract
BACKGROUND: Preliminary evidence suggests that many girls from breast cancer (BC) families are aware of their increased risk for BC. How this awareness impacts their psychosocial adjustment and health behaviors remains unknown.
METHODS: 11–19 YO girls at high-risk (HR) or population-risk (PR) for BC completed self-administered quantitative surveys informed by the Self-Regulation Theory of Health Behavior. Girls with a first or second-degree relative with BC were classified as HR. For hypothesis testing, we used simple linear and logistic regressions. To account for correlation of responses within families, we used robust (cluster-corrected) standard errors or Generalized Estimating Equations.
RESULTS: 47 PR and 89 HR girls have completed surveys. Age did not differ between groups (Mage = 15.6; SD=2.4). 30% of HR girls have a mother with BC. 67% of HR girls vs. 30% of PR girls reported self-perceived risk for adult BC to be “higher than other girls my age,” (p = &lt;0.01, Table 1).

Perceived risk was associated with an increasing number of first and second-degree relatives with BC (p = 0.002) and older age (p = 0.01). There was no evidence that the relationship between perceived risk and age was moderated by risk status (p = 0.740 for interaction terms). The majority of both HR and PR girls reported that there are things women and girls their age can do to prevent BC. (table 1) Perceived controllability of BC did not differ significantly by age or risk status. HR girls reported higher general anxiety (p = 0.07), but not depression than PR girls. HR girls more frequently reported tobacco use than PR girls (p = 0.05). HR girls also reported greater alcohol use, more frequent performance of self-breast exams and less frequent physical activity than PR girls, although these differences were not significant.
CONCLUSION: Girls from BC families are more likely to perceive themselves to be at increased risk for BC, to experience more general anxiety, and to have engaged more frequently in risk behaviors, particularly tobacco use. The majority of girls perceive BC to be preventable both for women in general and for themselves, suggesting a potential “teachable moment” among adolescents that might be sustainable across the lifespan. Further research evaluating knowledge and perceptions of breast cancer risk throughout adolescent development and differences among subgroups could inform strategies to optimize adolescent psychosocial responses to hereditary cancer risk and promote preventive health behaviors among both HR and PR girls.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-08-01.
Abstract P6-09-04: The Association of Low Level Arm Volume Increases with Lymphedema Symptoms Following Treatment for Breast Cancer
Authors: Skolny MN , Miller CL , Shenouda M , Jammallo LS , O'Toole J , Niemierko A , Taghian AG 
Published: August 2014

Abstract
Purpose/Objective: The symptoms associated with breast cancer-related lymphedema are well-documented, and include sensations of heaviness, swelling, and tightness in the upper extremity and trunk. However, the clinical significance of low-level arm volume changes frequently experienced by breast cancer patients is not well understood. We sought to determine the association of low level arm volume changes with patient-reported lymphedema symptoms in women treated for breast cancer.
Methods: 267 patients who underwent surgical treatment for breast cancer from 2010–2012 were identified from a cohort of patients prospectively screened for lymphedema at our institution. Patients were assessed with perometer arm volume measurements and a survey of lymphedema symptoms pre and post operatively, and at 3–7 month intervals thereafter. Inclusion in this analysis was limited to unilaterally affected women with ≥ 3 assessments and ≥ 6 months of post-surgical follow-up. Arm volume changes were quantified as Relative Volume Change (RVC): RVC = (A2*U1)/(U2*A1) − 1, where A1 is pre-operative arm volume and A2 is post-operative arm volume on the affected side, and U1 and U2 are arm volumes on the unaffected side at these time points. Low level arm volume change was defined as a measurement with RVC ≥ 5% &lt;10% at an assessment ≥ 3 months post-operatively. Actuarial univariate and multivariate regression analysis was performed to determine the association of low level arm volume change with patient-reported lymphedema symptoms and clinicopathological characteristics.
Results: Low level arm volume changes occurred in 21.7% (58/267) of patients during the follow-up period at a median of 10.4 months post-operatively. Median post-operative follow-up was 12.4 months and 5 assessments per patient. By actuarial univariate analysis, symptoms of larger arm, shoulder, or neck (p &lt; 0.001), tighter sleeve, sleeve cuff, or ring (p &lt; 0.001), and having undergone axillary lymph node dissection (p = 0.02) or regional lymph node radiation (p = 0.01) were significantly associated with low-level arm volume change. By actuarial multivariate analysis, only symptoms of larger arm, shoulder, or neck (p &lt; 0.0001) were associated with low level arm volume change.
Conclusions: This data suggests that patients may be symptomatic for lymphedema even when experiencing low level arm volume changes. These patients should be followed closely for progression of measured arm volume or heightened lymphedema symptoms suggesting progression of the condition.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-09-04.
Abstract P6-10-05: SU2C Phase 1b Trial of Dual PI3K/ mTOR Inhibitor BEZ235 with Letrozole in ER+/HER2− Metastatic Breast Cancer (MBC)
Authors: Mayer IA , Abramson VG , Balko JM , Isakoff SJ , Forero A , Kuba MG , Sanders ME , Li Y , Winer E , Arteaga CL 
Published: August 2014

Abstract
Background: Mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K, have been associated with antiestrogen resistance in ER+ BC. In general, antiestrogen-resistant cancers retain ER and responsiveness to estradiol, suggesting that treatment of ER+/PI3K mutant BC should include PI3K inhibitors plus endocrine therapy.
Methods: We are conducting a phase Ib open-label trial of letrozole (2.5 mg/d) with the dual PI3K/ mTOR inhibitor BEZ235 (400 mg BID, sachet formulation) in post-menopausal patients with ER+/HER2 negative MBC. Upon toxicity, BEZ235 was reduced to 400 mg in AM/ 200 mg in PM (dose level 1), and 200 mg BID (dose level 2), in a standard 3+3 de-escalation design. Treatment continues until unacceptable toxicity or disease progression. Tumor assessments are performed every 2 months. All tumor biopsies are being analyzed for PI3K pathway alterations.
Results: To date, 9 patients have been accrued; 6 on dose level 1 (400 mg BID) and 3 on dose level 1 (400 mg in AM/ 200 mg in PM). Of note, the latter 3 patients have been on treatment for less than 2 weeks at the time of abstract submission. Median age was 55 years (range 40–65); all patients had disease progression on previous endocrine therapy, and 100% had bone metastases and 30% had visceral metastases. Preliminary toxicities for dose level 1 cohort (400 mg BID) are summarized in the table below. The DLT was grade 3 mucositis, which happened less than 3 weeks of study initiation, in a total of 3 out of 6 patients. All grade 3 mucositis cases improved after BEZ235 interruption for 7 days and subsequent dose reduction. These 3 events triggered activation of the dose level 1 cohort (400 mg AM/ 200 mg PM). The first 3 patients on dose level 1 cohort (2 of which have PIK3CA mutated tumors) had their tumor assessment scans at 8 weeks post treatment initiation; all patients were found to have stable disease.

Discussion: The combination of letrozole/BEZ235 is still being evaluated in patients with ER+/HER2MBC. Safety, tolerability and preliminary antitumor activity data will be updated at the meeting.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-10-05.
Abstract P6-11-05: Novel sorafenib-derivatives induce apoptosis in breast cancer cells through STAT3 inhibition
Authors: Liu C-Y , Tseng L-M , Chang K-C , Chu P-Y , Su J-C , Shiau C-W , Chen K-F 
Published: August 2014

Abstract
Background: STAT3 has emerged as a novel potential anti-cancer target and its signaling is constitutively activated in various cancers including breast cancer. Our previous study has shown that STAT3 is a major kinase-independent target of sorafenib in HCC. (J Hepatol. 2011). Moreover, recent evidence has shown that p-STAT3 can be down-regulated by phosphatases, such as SHP-1 tyrosine phosphatase. We have designed and synthesized a series of sorafenib analogues devoid of sorafenib's kinase inhibition activity, some of which showed stronger p-STAT3 inhibition and apoptosis-inducing effects than sorafenib in HCC cells (Eur J Med Chem. 2011). Here, we tested the efficacy of novel sorafenib derivatives, SC-1 and SC-43, in breast cancer cells and examined the drug mechanism.
Methods: Six Breast cancer cell lines were used for in vitro studies. Cell viability was examined by MTT-assay. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. SHP-1 activity was measured by a phosphatase activity assay kit. In vivo efficacy of Sorafenib, and sorafenib derivatives were tested in xenografted nude mice.
Results: Sorafenib, SC-1 and SC-43 induced apoptosis in association with down-regulation of P-STAT3 and its downstream proteins Cyclin D1 and survivin in a dose-dependent manner in breast cancer cell lines (HCC-1937, MDA MB-468, MDA MB-231, MDA MB-453, SKBR-3, MCF-7) and the apoptotic effects induced by SC-1 and SC-43 were more potent than Sorafenib. Over-expression of STAT3 in MDA MB-468 cells protected cells from apoptosis induced by sorafenib, SC-1 and SC-43. Moreover, SC-1 and SC-43 up-regulated higher SHP-1 activity than sorafenib by in vitro phosphatase assays. Knockdown of SHP-1 by siRNA reduced apoptosis induced by SC-1 and SC-43. Importantly, SC-1 and SC-43 showed in vivo efficacy in MDA-468 xenografted tumor.
Conclusions: Our data indicated that inhibiton of p-STAT3 by up-regulating SHP-1 activity mediated apoptotic effects of sorafenib, SC-1 and SC-43 in breast cancer cells.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-11-05.
Abstract P6-14-02: Disease recurrence in the breast after treatment for occult primary breast cancer: a prospective, population-based study
Authors: de Maat Michiel FG , Steevens Jessie , Hulsewe Karel W 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-14-02.
Abstract PD01-08: Differences in estrogen receptor signaling in non-malignant primary ER-positive breast epithelial cells and breast cancer.
Authors: Lim E , He HH , Chi D , Yeung TY , Schnitt S , Liu SX , Garber J , Richardson A , Brown M 
Published: August 2014

Abstract
Background: The estrogen receptor (ER) is expressed in ∼70% of sporadic breast cancer and activates genes driving cell proliferation and tumorigenesis. We have previously performed genome-wide analysis of ER binding sites in MCF-7 breast cancer cells, and identified distinct mechanisms of ER signaling. We have also previously used EpCAM and CD49f as markers to enrich for viable ER-positive (ER+) cells obtained from non malignant breast tissue. Here, we seek to elucidate differences in ER signaling between non-malignant and ER+ breast cancer cells.
Methods: Primary breast epithelial cells were obtained from patients undergoing reduction mammoplasties and surgical excision of ER+ breast cancer. After dissociation of breast reductions into a single-cell suspension, ER+ mature luminal (ML; EpCAM+CD49f−) and luminal progenitor (LP; EpCAM+CD49f+) subpopulations were obtained by flow cytometry. Following estrogen stimulation, RNA was extracted for gene microarray analysis. ER chromatin immunoprecipitation and DNA sequencing (ChIP-seq) was performed. These results were compared to MCF-7 breast cancer cells.
Results: Reduction mammoplasty and ER+ breast cancer tissues were analyzed, and compared to MCF-7 cells. Gene expression profiles were different between non-malignant tissue and ER+ breast cancer cells following estrogen stimulation, with a 2–3 fold higher number of ER regulated genes in ER+ breast cancer compared to ER+ non malignant cells, and few overlapping estrogen regulated genes. Genes that promotes cell cycling and cell proliferation were downregulated in non-malignant tissue, but were upregulated in breast cancer cells (P &lt; 10–5). CYP1A1, a major estradiol metabolizing enzyme, was upregulated in normal cells but downregulated in ER+ breast cancer cells. Motif analysis of ER ChIP-seq data in normal and ER+ breast cancer tissues demonstrated an enrichment of ER motifs in the overlapping sites and an enrichment of FOXA1 motifs in ER+ breast cancer cells and TCF12 motifs in non-malignant ER+ epithelial cells.
Conclusions: There are contrasting differences in ER signaling between normal mammary and breast cancer cells, with estrogen having anti-proliferative effects in normal luminal cells compared to pro-proliferative effects in breast cancer. ER ChIP-Seq has identified TCF12 as a major co-factor in non-malignant breast tissue whilst FOXA1 is a major co-factor in ER+ breast cancer. Our data provides evidence for key alterations in ER-signaling during tumorigenesis, and identifies potential mechanisms to target cancer specific ER signaling.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD01-08.
Abstract PD02-01: Her2 expression measured by AQUA analysis on BCIRG-005 and BCIRG-006 predicts the benefit of Herceptin therapy
Authors: Christiansen J , Barakat N , Murphy D , Rimm DL , Dabbas B , Nerenberg M , Beruti S , Quinaux E , Hall J , Press M , Slamon D 
Published: August 2014

Abstract
Introduction: There have been disparate results reported in breast cancer testing for HER2 assessment as measured by protein expression or DNA amplification, yet both tests are routinely used to prescribe the drug Herceptin (trastuzumab, Genentech, So San Francisco, CA). Typically, immunohistochemistry (IHC) staining intensity of 3+ or FISH copy ratio of ≥2.0 are used to establish the cutoff between a negative and a positive result. However, it is unclear whether positivity is correlated with differential response to therapy. We used Automated Quantitative Analysis (AQUA) and a fluorescent immunohistochemical assay to measure HER2 expression in cases scored by central laboratory FISH and also receiving Herceptin therapy. The intentions of the study were two-fold: first, to provide further validation of the AQUA technology as applied to the clinical measurement of HER2 expression in breast cancer and second, to examine the potential of drug response stratification within those patients that are considered positive.
Methods: AQUA fluorescence IHC staining was performed on a multi-cohort tissue microarray (TMA) set. The assay was constructed in the Genoptix CLIA laboratory per ASCO/CAP guidelines and with a cutpoint that was validated against IHC (with FISH reflex). The trial specimens tested were from the BCIRG-005/006 studies. BCIRG-005 had n=1544 cases all assessed as FISH- while the 006 cohort had n=1477 cases all assessed as FISH+. Disease free survival (DFS) was used as the variable in subsequent modeling and analysis.
Results: The BCIRG 005 and 006 cohorts, examined in aggregate, allowed for an initial examination of agreement relationships between HER2 levels as assessed by AQUA scoring and HER2 levels as assessed by central lab FISH. Results indicated a 77% negative agreement, a 97% positive agreement and an 87% overall concordance agreement for a total of n=3021 cases. Additional Cox modeling of the patients that were enrolled as FISH+ and stratified for those who did or did not receive Herceptin treatment demonstrated a significant overall hazard ratio (HR = 0.75, CI=0.60,0.93) and when stratified for response to Herceptin, cases determined to be positive by AQUA showed significant benefit from treatment (HR = 0.66, CI = 0.52,0.85) in contrast to those who were scored as negative by AQUA that did demonstrate benefit from therapy (HR = 1.19, CI=0.71,1.97).
Conclusions: Analysis of the cases in this study originally determined to be HER2+ by FISH indicates that AQUA may improve predictions of which patients will benefit from Herceptin therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-01.