bluuebunny/crossref_metadata_2025_split huggingface dataset:
PL2-1: Macrophages as Novel Targets for Therapy in Breast Cancer.
Authors: Coussens LM 
Published: June 2012

Abstract
While BC has not historically been linked to underlying inflammation or infection, it exhibits tumor-associated inflammation marked by infiltration of innate and adaptive immune cells into developing tumors. In BC, macrophages are one of the most abundant innate immune cells present. BC-associated macrophages are regulated in part by colony stimulating factor 1 (CSF1), a key cytokine involved in monocyte/macrophage maturation, recruitment and activation, and its cognate receptor CSF1R. Macrophage presence in BC correlates with increased CSF1, increased vascular density, and worse clinical outcome. We reported that CD4+ T cells promote invasion and metastasis of mammary adenocarcinomas by directly regulating macrophage phenotype that in turn fosters invasive tumor growth, presence of circulating tumor cells and pulmonary metastasis. This preclinical data implied that women with BC heavily infiltrated by macrophages would have a worse clinical outcome as compared to tumors not heavily infiltrated with macrophages. We evaluated survival outcomes in 698 women with invasive BC treated with surgery alone and found that recurrence-free survival could be stratified based upon macrophage and T cell infiltration. Thus, we investigated CSF1 and CSF1R antagonists, in combination with standard-of-care chemotherapy (CTX) in mouse models of mammary carcinogenesis. We found that when macrophage infiltration in mammary adenocarcinomas was blocked, paclitaxel (PTX) chemosensitivity was increased, accompanied by development of productive anti-tumor immune responses and CD8+ cytotoxic T cell (CTL) infiltration. The combined effects of these changes were reduced primary tumor growth, 85% reduction in metastases and increased survival. In collaboration with clinical colleagues, we are currently evaluating the clinical benefit of macrophage modulation in preclinical models of BC to facilitate biomarker identification, and inform clinical trials of CTX in combination with macrophage-antagonists. Based on our preliminary data, we hypothesize that components of macrophage responses in BC can be identified to serve as biomarkers for risk stratification. And, that these components can be effectively targeted for therapeutic intervention, resulting in reduced late-stage BC development and metastasis when combined with CTX. LMC acknowledges generous support from the NIH/NCI (R01CA130980, R01CA13256, R01CA140943, R01CA15531), the Department of Defense (W81XWH-09-1-0342, W81XWH-10-BCRP-EOHS-EXP) and the Susan G Komen Foundation (KG111084)
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PL2-1.
S2-2: Luminal A Subtype Predicts Radiation Response in Patients with T1N0 Breast Cancer Enrolled in a Randomized Trial of Tamoxifen with or without Breast Radiation.
Authors: Fyles A , McCready D , Pintilie M , Shi W , Done S , Miller N , Olivotto I , Weir L , Liu F-F 
Published: June 2012

Abstract
Objectives
To determine the predictive effect of molecular subtyping using the six biomarker immunohistochemical panel in predicting ipsilateral breast relapse (IBR) in women age 50 and older with T1 and T2 node negative breast cancer in a randomized trial of tamoxifen (Tam) +/−whole breast radiation (WBRT).
Methods
Between December 1992 and June 2000, 769 women were randomized to WBRT and Tamoxifen (Tam, n=386) 20 mg daily for 5 years or Tam alone (n=383). Median age was 68 years, 639 (83%) had pT1 tumors. Intrinsic molecular subtype was determined using semi-quantitative analysis of ER, PR, Ki-67, HER2, EGFR and cytokeratin (CK) 5/6 on tissue microarrays constructed from tumor blocks from 172 of 345 available tumors. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype-nonbasal. Median follow-up was 10 years.
Results
IBR at 10 years was 13.8% with Tam compared to 5.0% with Tam/WBRT (p&lt;0.0001). Tumour size (HR 1.54, p=0.001), ER positive (HR 0.35, p=0.006), age (HR 0.96, p=0.014), and treatment with Tam/WBRT (HR 0.28, p&lt;0.0001) were significant factors for IBR. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67&lt;14%, n=95) had the lowest rate of IBR, 6.9% at 10 years with Tam alone and 4.5% with Tam/WBRT, p=0.4). In women aged 60 and over with Luminal A subtype IBR was 5.4% with Tam alone and 6% with Tam/WBRT (n=74, p=0.8). Luminal B (ER or PR positive, HER2 negative, Ki67&gt;14%, n=53) had an IBR of 23.8% with Tam alone and 0% with Tam/WBRT, p=0.012). Luminal HER2 (ER or PR positive, HER2 positive, n=10) and HER2−enriched (ER and PR negative, HER2 positive, n=14) demonstrated the highest risk of IBR.
Conclusions: Six marker IHC subtype appears to be predictive for radiation response in women over 50 with T1/2 node-negative breast cancer. Luminal A subtype demonstrated a low risk of breast relapse with Tam alone, particularly in women age 60 and older. These results require validation in additional specimens and clinical trials, but this subgroup represents a significant proportion of women (74/172 or 43%), who may be spared the inconvenience and side effects of breast radiation. In contrast, breast RT is beneficial in women with higher risk subtypes (Luminal B, HER2 enriched, basal). Limitations of this analysis include the relatively small numbers of patients and the low event rate in smaller subgroups.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S2-2.
S3-7: Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial.
Authors: Hortobagyi GN , Piccart M , Rugo H , Burris H , Campone M , Noguchi S , Gnant M , Pritchard KI , Vittori L , Mukhopadhyay P , Sahmoud T , Lebwohl D , Baselga J 
Published: June 2012

Abstract
Background: The mTOR pathway is constitutively activated in hormone-resistant advanced breast cancer (ABC). In phase II trials, everolimus (EVE) showed promising efficacy both as monotherapy and in combination with endocrine therapy in patients with estrogen receptor-positive (ER+) ABC. This double-blind, placebo-controlled, phase III study evaluated EVE plus exemestane (EXE) in patients with ER+ ABC refractory to letrozole or anastrozole.
Patients and Methods: Eligible patients were randomized (2:1) to EXE (25 mg/day) with EVE (10 mg/day) or with matching placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, quality of life (QoL), and safety.
Results: 724 patients were randomized (485: EVE+EXE; 239: EXE). Baseline characteristics were well balanced; median age was 62 years, 56% had visceral involvement, and 84% had documented benefit from previous endocrine therapy, which included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy for advanced disease (25%). This analysis is based on 457 events and median follow-up of 12.5 months. PFS by investigator assessment showed a hazard ratio (HR) of 0.44 (95% CI: 0.36−0.53) and a median duration of 7.4 (EVE+EXE) vs 3.2 months (EXE) (P&lt;1 × 10−16) and 12-month estimate of 31% vs 10%. PFS by central assessment showed an HR of 0.36 (95% CI: 0.28−0.45) and a median duration of 11.0 (EVE+EXE) vs 4.1 months (EXE) (P&lt;1 × 10−16) and 12-month estimate of 48% vs 18%. Response rates and clinical benefit rate were also higher for EVE+EXE (12.0% vs 1.3% and 50.5% vs 25.5%). A total of 138 patients died; 17.3% in the EVE+EXE arm and 22.6% in the EXE arm.
The most common grade 3/4 adverse events were stomatitis (8% vs 1%), anemia (7% vs 1%), hyperglycemia (5% vs &lt; 1%), dyspnea (4% vs 1%), and fatigue (4% vs 1%) for the EVE+EXE and EXE groups, respectively. Grade 3 pneumonitis was observed in patients receiving EVE (3% vs 0%). No difference in time to deterioration of QoL was observed. EVE increased EXE steady-state Cmin and Cmax levels by 45% and 64%, respectively, with no difference in estradiol levels. Serum markers of bone resorption and bone formation increased in the EXE arm and generally decreased in the EVE+EXE arm.
Conclusion: The addition of EVE to EXE is associated with significant and sustained prolongation of PFS. Adverse events were higher in the combination arm but manageable by dose interruption and/or reduction and did not affect QoL. EVE in combination with an aromatase inhibitor is a promising therapeutic option for women with hormone receptor-positive advanced breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S3-7.
S4-5: Comparison of PAM50 Risk of Recurrence (ROR) Score with OncotypeDx and IHC4 for Predicting Residual Risk of RFS and Distant-(D)RFS after Endocrine Therapy: A TransATAC Study.
Authors: Dowsett M , Lopez-Knowles E , Sidhu K , Pineda S , Cowens JW , Ferree S , Storhoff J , Schaper C , Cuzick J 
Published: June 2012

Abstract
Aim: To assess the performance of the risk of recurrence (ROR) score in predicting RFS and DRFS for postmenopausal patients with primary ER+ breast cancer treated with anastrozole or tamoxifen and compare this with the performance of Oncotype Dx and IHC4 for both N0 and N+ patients.
Background: OncotypeDx Recurrence Score (RS) is used to assess RR after endocrine therapy in primary ER+ breast cancer and is valid for both tamoxifen and anastrozole (Dowsett ref). IHC4 is a 4-panel set of IHC markers (ER, PgR, HER2, Ki67) that was shown to provide as much prognostic accuracy as RS in the translational arm of the ATAC trial (TransATAC) of anastrozole versus tamoxifen alone or combined and subsequently independently validated (Cuzick et al, JCO, 2011, in press). PAM50 is 50-gene test that has been optimised to separate intrinsic disease subtypes and is used to generate a ROR score. Good correlation has been shown between the ROR and RS but no large scale comparisons of their ability to predict clinical outcome have been conducted.
Methods: PAM50 analysis was conducted using NanoString technology on 125 ng RNA extracted from all 1026 samples from the TransATAC study that had at least 500ng RNA available. Nodal status was known on 986: N+, 271; N-neg 715. ROR scores were calculated and their relationship with RFS and DRFS assessed in both the N-neg and N+ categories. The prognostic value of ROR when added to standard clinical variables was assessed using the likelihood ratio chi-square. Finally, the relative accuracy of prognosis in this patient population using ROR, RS and IHC4 was evaluated by comparing the C-index for each test.
Results: Results are currently being derived and will be presented in full.
Discussion: This is the first large-scale clinical comparison of 2 prominent multi-gene predictors for use in FFPE material. The results will be instrumental in defining the preferred method for use in assessing residual risk of recurrence in patients treated with endocrine therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S4-5.
S5-2: PAM50 HER2−Enriched Subtype Enriches for Tumor Response to Neoadjuvant Anthracyclines/Taxane and Trastuzumab/Taxane Containing Regimens in HER2−Positive Breast Cancer.
Authors: Cheang MCU , Prat A , Fan C , Perou CM 
Published: June 2012

Abstract
Background: Patients with clinically HER2−positive (clinHer2+) tumors often receive trastuzumab in combination with chemotherapy as their standard of care. This study sought to determine the predictive value of the HER2−enriched (HER2−E) molecular subtype for sensitivity to neoadjuvant anthracycline/taxane containing chemotherapy and a trastuzumab plus taxane-based regimen within clinHer2+ disease.
Materials and methods: Gene expression data on pre-treatment fresh-frozen tumor tissues were collected from a combined cohort of MDACC/I-SPY trial (GSE25055/65), and the XeNA trial (GSE22358). Patients from MDACC/I-SPY were treated with doxorubicin/cyclophosphamide (AC) or 5-fluorouracil/epirubicin or doxorubicin/C (FEC or FAC) sequentially with paclitaxel. All patients from XeNA received capecitabine/docetaxel (and trastuzumab if clinHer2+). Intrinsic subtypes were determined using PAM50. Chisquare test and multivariable logistic regression analysis were used to test significance of association between subtype and pathological complete response (pCR or residual cancer burden [RCB] 0/1) and residual disease (RD or RCB2/3) adjusted with pre-treatment tumor size. Kaplan Meier was used for distant relapse-free survival (DRFS) estimates.
Results: For the MDACC/I-SPY cohort (n=595), pCR rates for intrinsic subtypes were 3% (5/168) for LumA, 16% (14/90) for LumB, 33% (23/69) for HER2−E and 37% (76/208) for Basal-like. Tumors achieving RCB0/1 were significantly associated with better DFRS compared to those tumors with RCB 2/3, even within each intrinsic subtype. The 5-year DFRS for HER2−E with RCB0/1 and RCB2/3 was 100% and 31% (p=0.007), respectively. ClinHer2+ status was also significantly associated with pCR (34% vs. 19%, p=0.016). Strikingly, among the clinHer2+ tumors (n=47), 75% (12/16) of the responders were classified as HER2−E (Table 1A) and those tumors that were clinHer2+/HER2−E had 6 times odds to achieve pCR when compared to clinHer2+/non-HER2−E. In the XeNA trial (n=122), the HER2−E subtype was significantly associated with response, composing 85% (7/8) of the clinHer2+ who achieved a pCR. Finally, clinHer2+/HER2−E tumors were 34 times more likely to achieve pCR than clinHer2+/non-HER2−E tumors (Table1B).

Conclusion: The sensitivity of clinHer2+ tumors to neoadjuvant anthracycline/taxane-based regimens, and trastuzumab-based chemotherapy is mainly contained within tumors of the HER2−E subtype. Given that this molecular subtype cannot simply be recapitulated using clinical ER and HER2 status, our results highlight the importance of identifying patients with HER2−E tumors as this appears to greatly enrich for responsiveness and treatment benefit.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S5-2.
Abstract A108: Racial/ethnic disparities in prostate cancer treatment persist
Authors: Orom Heather , Brasel Alicia , Underwood Willie 
Published: June 2012

Abstract
Background: Adjusting for stage and grade, Black and Hispanic men have lower prostate cancer (PCa) survival than White men. These survival differences are most likely multifactorial, but they have, in part, been attributed to lower receipt of definitive treatment (prostatectomy or radiation therapy vs. active surveillance or hormone therapy alone). Disparities in receipt of definitive treatment have been well documented in older SEER cohorts; however, we do not know if they persist. Therefore, we used the Surveillance Epidemiology End Result (SEER) Tumor Registry to analyze patterns of PCa treatment by race/ethnicity (Black, Hispanic, Asian/Other, and White men) in men diagnosed with clinically localized PCa between 2004–2007.
Method: Logistic regression was performed to determine whether there were racial/ethnic differences in the odds of receiving definitive treatment, adjusting for age, year of diagnosis, grade, PSA, National Comprehensive Cancer Network (NCCN) risk, SEER site, and marital status. We then examined the relative adjusted odds of receiving definitive treatment at each level of NCCN risk for Black, Hispanic and Asian/other men compared to White men.
Results: Data from 175,366 (White 130,096, Black 21,503, Hispanic 14,412, and Asian/other 9,355) men were included in the analyses. In the overall sample, Black men (OR=0.72, 95% CI=0.69-0.75) and Hispanic men (OR=0.92, 95% CI=0.88-0.96) had lower odds of receiving definitive therapy compared to White men. For Black men, this remained true at every level of risk, even among men with high (OR=0.62, 95%CI=0/55-0.69) and very high risk prostate cancer (OR=0.73, 95%CI=0.67-0.80). Hispanic men with high risk disease had lower odds of receiving definitive treatment than their White counterparts (OR=.80, 95%CI=.70-.90). However, the gap was not significant among Hispanics and Whites with the highest risk disease (OR=1.0, 95%CI=0.90-1.11). For Asian/other men, the odds of receiving definitive treatment were not significantly different than for White men, either overall or when stratified by NCCN risk.
Racial/ethnic differences in the receipt of definitive treatment persist even among men with high risk disease. In order to address PCa treatment disparities and impact racial/ethnic disparities in PCa survival, further investigation of PCa treatment decision making is warranted.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A108.
Abstract A20: HPV and HPV vaccine education intervention: Effects on parents, healthcare staff, and school staff
Authors: Reiter Paul L. , Stubbs Brenda , Panozzo Catherine A. , Whitesell Dianne , Brewer Noel T. 
Published: June 2012

Abstract
Background: Increasing knowledge about HPV and HPV vaccine is a potentially important way to increase vaccination rates, yet few education interventions have addressed these topics. We report the results of an education intervention targeting three key groups who have contact with adolescent females.
Methods: We conducted HPV education intervention sessions during 2008 and 2009 in Guilford County, North Carolina. Guilford County has a higher proportion of African American residents compared to North Carolina as a whole, as well as one of the highest cervical cancer mortality rates in the state. Parents (n=376), healthcare staff (n=118), and school staff (n=456) attended the one-time education sessions and completed self-administered surveys. Analyses used mixed regression models.
Results: Participants had relatively low levels of objectively assessed HPV and HPV vaccine knowledge prior to the intervention. The education intervention increased self-rated HPV knowledge among all three key groups (all p&lt;0.001), as well as objectively assessed knowledge about many aspects of HPV and HPV vaccine among healthcare and school staff members (all p&lt;0.05). Although all groups experienced an increase in their self-rated knowledge, the largest increase was seen among parents, with healthcare and school staff experiencing smaller increases (p&lt;0.05). Following the intervention, over 90% of school staff members believed HPV and HPV vaccine education is worthwhile for school personnel and that middle schools are an appropriate venue for this education. Most parents (97%) and school staff members (85%) indicated they would be supportive of school-based vaccination clinics.
Discussion: An important first step in increasing HPV vaccination rates among adolescent females in the US is to improve knowledge levels among key groups influential to adolescents’ vaccination behaviors. In this study, we demonstrated that a simple education intervention greatly improved objectively assessed and self-rated HPV and HPV vaccine knowledge levels among parents, healthcare staff, and school staff members. Such interventions offer a relatively low effort and potentially effective strategy for increasing HPV vaccination.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A20.
Abstract A32: Implementing a breast cancer treatment patient decision aid in a medically underserved population in Texas
Authors: Rustveld Luis , Jibaja-Weiss Maria 
Published: June 2012

Abstract
Background: Decision aids are designed to help patients make informed decisions about medical treatment options. We developed and evaluated the effectiveness of culturally and linguistically appropriate breast cancer patient decision aid, “A Patchwork of Life” (PLife), targeted at medically underserved women with limited literacy. The PLife is a computer-based learning environment that involves two key components, soap opera segments and related learning modules designed to support breast cancer (Stages I-IIIA) surgery decision-making and to encourage communication about treatment decision with their provider, relatives and friends. The objectives of the current project are to implement the Plife program at one of the National Community Cancer Center Program (NCCCP) sites, in Austin Texas to: 1) evaluate the effectiveness of the implementation of the PLife program at the NCCCP clinic site by conducting an assessment of program outcomes with various stakeholders – patients, physicians, and patient navigator; 2) evaluate patients’ and providers'perceptions of the usefulness of the intervention for aiding in their decision-making.
Experimental Procedures: We will recruit 60 patients diagnosed with Stage I-IIIA breast cancer over 18 months. Patients will be identified through pathology and other medical records and physician referrals. Those who consent will complete all baseline assessments before implementation of the PLife decision aid. A Patient Navigator will arrange for a convenient time for the patient to view the program. Immediately after viewing the program, patients will answer a questionnaire rating the program. Follow-up data collection with patients will take place via phone 2-weeks after viewing the program. Measures to be collected at the 2-week follow up include breast cancer knowledge, decisional conflict, and treatment preferences, and provider perception questionnaires. Questionnaires will be administered in Spanish and English.
Expected Results and Conclusions: The proposed project will enable the NCCCP site to significantly enhance breast cancer education, awareness and navigation for the underserved breast cancer patients who currently do not receive education or navigation services utilizing a tool that has been proven to assist patients with limited literacy in making informed breast cancer treatment decisions.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A32.
Abstract A53: Disparities in health information needs among long-term cancer survivors
Authors: Kent Erin E. , Arora Neeraj K. , Bellizzi Keith M. , Aziz Noreen M. , Hamilton Ann S. , Oakley-Girvan Ingrid , Rowland Julia H. 
Published: June 2012

Abstract
Understanding the role of follow-up care on information needs in long-term cancer survivors is an important and understudied area for research and intervention. We examined health information needs in 1157 cancer survivors 4–14 years post-diagnosis from a population-based survey: the Follow-up Care Use among Survivors (FOCUS) study. Endorsement of six information needs categories (tests/treatments, side effects/symptoms, health promotion, interpersonal/emotional, insurance, and sexual functioning/fertility), total number of needs, and information self-efficacy were regressed on socio-demographic and clinical variables, quality of recent follow-up care, receipt of treatment summary, type of main follow-up doctor, and perceived social support. In the multivariate models, survivors who were younger, African American, and those with lower support (P &lt; 0.05) reported a significantly higher number of needs. Non-whites expressed significantly higher interpersonal/emotional and insurance information needs (P &lt; 0.05). Survivors who did not receive but wanted a written treatment summary were more likely to indicate higher needs in side effects and symptoms (odds ratio: 2.74, 95% CI: 1.54–4.87) than those who had received a treatment summary. After adjustment, number of information needs was inversely related to information self-efficacy (P &lt; 0.05). The pattern of needs reporting suggests persistent health disparities in access to important health information in long-term survivors. Findings also suggest the need for survivorship care planning to equip survivors with comprehensive health information and to consider tailored approaches for communicating this information to diverse survivor populations.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A53.