bluuebunny/crossref_metadata_2025 huggingface dataset:
PD05-07: Prospective Validation and Characterization of HER2 Positive Circulating Tumor Cells in Patients with HER2 Negative Metastatic Breast Cancer.
Authors: Olson EM , Flores LM , Najita JS , Curley C , Jeong J , Murray K , Savoie JJ , Winer EP , Krop IE
Published: June 2012

Background: Circulating tumor cells (CTCs) with evidence of HER2 amplification can occur in patients (pts) with clinically HER2 negative metastatic breast cancer. While these findings potentially have profound implications for CTCs as a biomarker for treatment, prospective validation and characterization of this subgroup is necessary.

Methods: We created a prospective cohort of pts with metastatic breast cancer that were HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Blood samples were collected at study entry and then again at ≥ 3 weeks if available. CTCs were enumerated by a modification of the Veridex CellSearch Profile kit. FISH was performed on each CTC sample and reported as positive if the HER2/CEP17 ratio was ≥ 2.0. Analyses are descriptive.

Results: 66 pts were consented for study and this report includes the 65 pts with detectable CTCs. Median number of CTCs was 226 (range 112 to > 3000). At initial testing, 23 pts (35%) had HER2 positive CTCs, median HER2:CEP17 ratio of 3.4. 50% (11 of 22) of the pts with lobular or ductal/lobular histology had HER2 amplified CTCs, compared to only 27% (10 of 36) of patients with ductal histology. Women with ER positive disease had HER2 positive CTCs in 40% of cases (20 of 49) compared to 19% of ER negative pts (3 of 16). To assess concordance of HER2 amplification of CTCs over time, 34 pts consented to be retested at a median 5.9 weeks after initial screening (range 3.3 - 17 weeks) and all but 1 had detectable CTCs. Baseline characteristics of these 34 pts were similar to the original population, with HER2 amplified CTCs detected in 35% (12 of 34) pts at initial screening. HER2 positive CTCs were concordant at time of retesting in 83% (10 of 12) pts; the 2 women with discordant CTCs were receiving HER2 directed therapy. Of the pts with HER2 negative CTCs at initial screening, 81% (17 of 21) continued to have HER2 negative CTCs at time of retesting.

Conclusion: We observed a higher prevalence of HER2 positive CTCs among pts with ER positive disease and evidence of lobular histology. The presence of HER2 positive CTCs is concordant over time in the majority of pts. The functional significance of HER2 positive CTCs in patients with clinically HER2 negative breast cancer will be tested in a prospective study with HER2−directed therapy.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-07.
PD06-01: Molecular Classification with 21 Gene Assay (Oncotype DX®) Shows in 196,967 ER Positive Patients High Frequency of Low Recurrence Score [LRS] in Both Node Positive (N+) and Negative (N-) Breast Cancer (BrCa) Cohorts. Definition of Chemoresistance Based on LRS with Cost and Guideline Implications.
Authors: Ragaz J , Wilson KS , Wong H , Muraca G , Hryniuk W , Bajdik C
Published: June 2012

BACKGROUND : Key retrospective analyses have shown no benefit from adjuvant CT [CT] in ER+, N-ve and N+ve BrCa pts with LRS by Oncotype DX assay. (For N-ve, hazards [RR] = 1.31, 95% C.I.: 0.46, 3.78 (Paik et.al., 2006); for N+ve, RR=1.01, 95% C.I.: 0.54, 1.93 (Albain et.al. 2009)]. LRS (RS<18) can therefore be equated to CT resistance (CTRES).

OBJECTIVES : 1. To determine the frequency of CTRES determined by Oncotype DX in the Genomic Health database of ER+, N-ve and N+ve pts. 2. To estimate the net cost savings resulting from avoidance of CT for CTRES pts, based on universal Oncotype DX testing in ER+ pts being considered for CT.

METHODOLOGY STEP 1 : Oncotype DX results were analyzed according to nodal status in the 196,967 ER+ tumor samples for CT candidates submitted to Genomic Health between Jan 2007 - Apr 2011.

STEP 2 : We then calculated the $ cost saved, result of Oncotype DX, assuming:

i. of new BrCa pts, 42% could be candidates Oncotype DX and CT (ER+, high risk N-ve; and all ER+ N+ve)

ii. either 50% or 100% CT avoidance — according to oncology practice — among LRS cases, estimating the CT cost/pt = $15,000 US; and Oncotype DX cost/pt = $4,000 US.

RESULTS — STEP 1 LRS based on Oncotype DX was more prevalent in N+ pts (chi sq p <0.0001)

RESULTS — STEP2 ; CT Cost [in millions, USD] / 1,000 newly diagnosed cases who are CT and Oncotype DX condidates, of whom 50% [conservative estimates] will have LRS

Thus, in USA, with 225,000 new BrCa pts / year, and 94 500 [42%] candidates for Oncotype DX, over 47,250 pts will have LRS, with overall savings of $330.8 mil/year with 100% CT avoidance. In Canada, with 25,000 estimated new BrCa pts/year, corresponding savings will be $46.2 mil/year.

CONCLUSIONS:

1. Low RS status, presently the most reliable CTRES biomarker, is expressed with higher frequency among N+ve (59%) vs N-ve (54%) ER+ breast cancer pts.

2. If all eligible cases had the Oncotype DX test, and all with LRS would avoid CT, close to 50,000 pts in USA, and over 5,200 in Canada will be spared ineffective CT and associated toxicity / year, with hundreds of million dollars saved each year.

3. On principles of ethics and economy, these data suggest that until new research refines the molecular classification of BrCa for higher efficacy, and with lower cost and more practical access:

a. universal OncotypeDx testing for pts should be performed for all ER+ breast cancer pts candidates for CT;

b. management guidelines should be changed to avoid CT in all LRS pts, irrespective of nodal status;

c. until prospective randomized trials confirm CT benefit among LRS pts, its use should be considered investigational.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD06-01.
PD08-06: ERK2 Promotes Stem Cell-Like Characteristics in Triple-Negative Breast Cancer.
Authors: Bartholomeusz C , Saso H , Dadbin A , Kazuharu K , Hortobagyi GN
Published: June 2012

Background: Triple-negative breast cancer (TNBC) is resistant to targeted therapies such as hormonal therapy and HER2−targeted therapies. Thus, no specific targeted therapy is currently available for TNBC. ERK2, a component of the MAPK pathway, plays an important role in epithelial-mesenchymal transition (EMT) in MCF-7-10A, a nontransformed human mammary epithelial cell line and is required for full acquisition of stem cell-like characteristics. Inhibition of ERK2 dramatically reduces cell growth, whereas inhibition of ERK1 significantly facilitates proliferation. ERK1 mutant mice have a strikingly milder phenotype than ERK2 mutant mice, which die early in development. In addition, we have shown that the upstream target of ERK, MEK, may be a target for treating TNBC with the MEK inhibitor selumetinib. Our reverse-phase protein array analysis showed that of patients with TNBC, those with ERK2-overexpressing tumors were at higher risk of death than those with low-ERK2-expressing tumors. Therefore, we hypothesized that ERK2 promotes the tumorigenesis and metastasis of TNBC. We sought to determine the role of ERK2 in the tumorigenic and metastatic activities in TNBC and whether ERK2 is required for acquisition of stem cell-like characteristics in TNBC.

Methods: We studied the role of ERK1 and ERK2 in the TNBC cell line SUM-149. We used shRNA to specifically knockdown ERK1 and ERK2 (shERK1 and shERK2) and examined whether knocking down ERK1 and ERK2 correlated with EMT regulation, migration, and tumorigenicity in TNBC cells.

Results: Compared with parental SUM-149 cells, stable clones that constitutively expressed shERK1 or shERK2 showed no difference in growth rate. However, knocking down ERK2 significantly inhibited migration and the acquisition of stem cell-like characteristics (CD44+/CD24-) in SUM-149 cells in vitro. In addition, knockdown of ERK2 also inhibited anchorage-independent growth, an indicator of in vivo tumorigenicity, whereas knockdown of ERK1 did not inhibit anchorage-independent growth. However, inhibition of ERK1 or ERK2 in 2D or 3D cell culture did not correlate with changes in epithelial and mesenchymal markers by western blot analysis. Conclusion: Our data demonstrate that ERK2 may promote the tumorigenesis of TNBC via enriching cancer stem cells. Our long-term goal is to develop ERK-targeted therapy for TNBC.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-06.
PL2-1: Macrophages as Novel Targets for Therapy in Breast Cancer.
Authors: Coussens LM
Published: June 2012

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

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<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<0.0001) were significant factors for IBR. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67<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>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

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<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<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 < 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

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

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

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

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<0.001), as well as objectively assessed knowledge about many aspects of HPV and HPV vaccine among healthcare and school staff members (all p<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<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

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

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 < 0.05) reported a significantly higher number of needs. Non-whites expressed significantly higher interpersonal/emotional and insurance information needs (P < 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 < 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.
Abstract A63: Outcome disparities in high-grade soft tissue sarcomas: A comprehensive cancer center's experience
Authors: Lewis Valerae O. , DeComas Amalia M. , Wen Sijin , Lin Patrick P. , Moon Bryan S. , Satcher Robert L. , Pollock Raphael E. , Thall Peter F.
Published: June 2012

Recent studies in cancer treatment have identified higher perioperative mortality and lower long-term survival among blacks relative to whites. The largest disparities in survival occur among patients with solid tumors for which appropriate and high quality treatment is an important prognostic factor. Soft tissue sarcomas (STS) require specialized multidisciplinary care. However, the influence of race/ethnicity has not been examined.

A single institution retrospective study was performed on all high grade STS of the extremities treated from 1991 thru 2007. Multivariate analyses including gender, age, race, disease stage, tumor size, presentation at multidisciplinary conference, prior surgery, comorbidities, definitive surgery, margin, chemotherapy, radiation, distance to hospital, income and payor method were conducted to assess association with overall survival (OS) and event-free survival (EFS). Distributions of patient characteristics were assessed, unadjusted OS and EFS distributions were estimated and compared between subgroups, and effects of covariates on OS and EFS were assessed using standard statistical techniques.

The study included 697 patients (311 females and 386 males) with high grade STS. 9.6% were African American (AA), 73.9% were White and 16.5% were Hispanic. 7.0 yrs (95%CI: 6.6–7.4 yrs). Age, male, AA, large tumor size, chemotherapy and no insurance were significantly associated with shorter OS and EFS. Stage 3/4 disease and radiation were significantly associated with OS and EFS, respectively. African Americans presented with larger tumor size (p<0.0001), a higher rate of metastatic disease (p=.001), and in univariate analyses, had worse OS (p<0.001) and EFS (p=.0022). Patients with low/middle income or without medical insurance had worse OS. African Americans and Hispanics had significantly lower income compared to Whites (p<0.0001), and were less likely to have medical insurance (p<0.0001). Among the uninsured, African Americans had worse OS (p<0.0001).

Despite treatment at a comprehensive cancer center, African Americans with STS universally had poorer outcomes. The cause for these racial disparities is multifactorial and encompasses both patient factors and health care system effects. The higher mortality of African Americans seen here may be due to underuse of primary medical care, resulting in later disease stage at diagnosis.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A63.
Abstract A67: IL-16 variants associated with prostate cancer risk in African Americans
Authors: Batai Ken , Beisner Erin , Shah Ebony , Castaneda Lauren , Smith Demetria , Murphy Adam , Kittles Rick A.
Published: June 2012

Background: Prostate cancer (Pca) is the most common type of cancer among men in the United States, and its disproportionate incidence and mortality rates among ethnic groups are likely due to a combination of genes and environmental factors. While genome-wide association studies (GWASs) of European descents have identified candidate loci associated with Pca risk, including rs4072111 located in IL-16, the replication studies in African Americans (AAs) have been inconsistent, and GWASs have not yet produced many findings to resolve Pca health disparities. IL-16 is over-expressed in tumor cells possibly mediating expression of other cytokines that promote tumor growth. Here we explore SNP variation in IL-16 in AAs and test for association with Pca in AAs.

Method: Two hundred and seventy-seven (277) tagging SNPs spanning IL-16 (79.20Mb to 79.45Mb on chromosome 15) were genotyped in 496 AA Pca cases and 501 controls from Washington, DC. In order to replicate our findings, 11 of the SNPs were also typed in additional 400 AA Pca cases and controls from Chicago, IL. One hundred (100) unlinked ancestry informative markers were also typed for each sample. West African genetic ancestry estimates were obtained using STRUCTURE. We tested for allelic association and calculated odds ratios using logistic regression, adjusting for West African ancestry and age. Empiric p-values were obtained by adaptive permutation.

Results: Our first stage analyses revealed that a cluster of 20 IL-16 SNPs were significantly associated with Pca risk. The strongest association was found at rs7175701 (P=1.2 × 10−8), which lies within intron 26 of IL-16. In the replication population, two SNPs, slightly linked to rs7175701, but within the 3′UTR region were also strongly associated with Pca risk (P<0.005).

Our study provides evidence that IL-16 polymorphisms likely play a role to Pca susceptibility in AAs. Many of the significantly associated SNPs are linked to rs11325 which is a candidate SNP for a miRNA target region in IL-16. Although the exact mechanism is unclear, additional functional studies are warranted.

Impact: Our findings are significant given that there has been limited focus on the role of IL-16 genetic polymorphisms on Pca risk in AAs. Understanding the role of cytokines such as IL-16 in tumor growth in diverse populations is important, and could likely lead to the development of useful biomarkers for cancer screening and/or potential therapeutics.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A67.
Abstract A7: Young adult cancer survivors and substance abuse: Results from the U.S. National Health Interview Survey, 1997–2009
Authors: Clarke Tainya C. , Caban-Martinez Alberto J. , Ocasio Manuel A. , Clark John , Kachan Diana , Arheart Kristopher L. , Lee David J.
Published: June 2012

Introduction: The five-year survival rates for young adult cancers continue to increase. Nonetheless, these young adult survivors may experience health complications or physical late effects that contribute to negative lifestyle behaviors potentiating the use of gateway drugs (e.g. alcohol and cigarettes). Examination of these negative behaviors during emerging adulthood (i.e., ages 18–24) may be particularly critical, as this developmental period is characterized by significant change, instability, identity exploration, and experimentation. In the present study, we examine the use of cigarettes and risky alcohol consumption among U.S. young adult cancer survivors.

Methods: We analyzed data on 39,433 U.S. young adults age 18–24 participating in the 1997–2009 National Health Interview Survey, who reported on their cigarette use and alcohol consumption, and socio-demographic characteristics.

Results: Among all youth, youth workers are almost twice as likely to smoke cigarettes when compared to their unemployed peers and Whites were more likely to engage in these negative behaviors when compared to their Black peers. There was no significant difference in alcohol or cigarette use by cancer history among young people. Approximately 35% of young cancer survivors were smokers and 70% current drinkers. Analyses did not reveal any significant reports of risky drinking.

Conclusions: Periodic clinical assessments for substance use among cancer survivors is important, particularly during the transition from late adolescence to emerging adulthood when baseline rates are relatively high compared to other ages. Research on processes involved in a young cancer survivors’ decisions to use substances will provide better insight regarding how best to intervene and who to include in educational interventions.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A7.
Abstract B11: Effect of patient navigation on colorectal cancer screening in a community-based randomized controlled trial of urban African American Medicare beneficiaries
Authors: Horne Hisani N. , Markakis Diane , Phelan Darcy F. , Pollack Craig E. , Wenzel Jennifer , Garza Mary A. , Shapiro Gary R. , Bone Lee , Johnson Lawrence , Ford Jean G.
Published: June 2012

Background: In recent years, colorectal cancer screening rates have increased steadily in the United States, though racial and ethnic disparities persist. We investigated the effect of a patient navigation intervention on adherence to colorectal cancer screening guidelines among African American older adults in Baltimore, MD.

Methods: We examined data collected from the Cancer Prevention and Treatment Demonstration (CPTD), a community-based randomized, controlled trial. Our study population consisted of 661 African American men and women aged 65 to 75 years who were Medicare beneficiaries and residents of Baltimore City. Participants were randomized to receive either printed educational materials only (PEM) or the addition of a patient navigator (NAV). The Johns Hopkins trained and certified patient navigator assisted participants with identifying and overcoming potential barriers to cancer screening. Self-reported colorectal cancer screening data were collected at baseline and at one-year follow-up through inperson interviews. Rates of screening between the two groups were examined using multivariable logistic regression modeling. All participants irrespective of their baseline screening status were included in calculating the adjusted odds of completing colorectal cancer screening during the follow-up period.

Results: At baseline, 68% of the PEM group and 71% of the NAV group (P = 0.45) reported being up-to-date with colorectal cancer screening, defined as having either a fecal occult blood test (FOBT) within one year or colonoscopy/sigmoidoscopy within ten years of randomization. At the one-year follow-up visit, participants in the NAV group were more likely to report having undergone any colorectal cancer screening during the previous year, compared to the PEM group, 54% versus 46%, though this did not reach statistical significance (P = 0.12). After adjusting for age, gender, number of co-morbidities, education, participants’ health perception and level of health literacy, individuals in the NAV group were more likely to report being screened by colonoscopy/sigmoidoscopy (OR, 1.53; 95% CI, 1.07–2.18) compared to those in the PEM group. Individuals who underwent patient navigation did not have a statistically significant change in the likelihood of reporting a FOBT compared to the PEM group.

Conclusions: In a population of urban African American older adults, patient navigation was effective in increasing the likelihood of screening by colonoscopy/sigmoidoscopy but not fecal occult blood testing at one-year follow-up. The lack of effect on screening by FOBT likely represents the relatively low rate of provider utilization of this screening modality in the target population.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B11.
Abstract B12: GMaP and BMaP community collaboration: Addressing colorectal cancer on a regional level
Authors: Thompson Beti , Klonoff Elizabeth , Harbach Heidi , Iweriebor Ebere
Published: June 2012

In the western Region, colorectal cancer is a leading cause of cancer incidence and mortality with well-documented disparities among the various racial and ethnic groups represented in this Region. Early detection is key to colorectal cancer; and it has the advantage of offering preventive care when polyps are removed during colonoscopy. As a GMaP/BMaP partnership, the Fred Hutchinson Cancer Research Center and San Diego State University have been working on building a research hub in Region VI (Alaska, Washington, Oregon, California, Hawaii, Guam, and American Samoa); to conduct a needs assessment of colorectal cancer and resources to decrease colorectal cancer in the Region. A review of secondary data provided us with information regarding colorectal cancer incidence and mortality among underserved populations in the Region. We also developed and distributed SurveyMonkey questionnaires to community members and academic partners in Region VI. We constructed a needs assessment of colorectal cancer in Region VI and work that was being done to address colorectal cancer. A key finding was that community/academic partnerships are needed to launch activities to control colorectal cancer in the Region. The needs assessment indicates that communities are key partners in activities to reduce the rate of colorectal cancer incidence and mortality. All of the state comprehensive cancer programs in the region are focusing on colorectal cancer. Collaboration between community and academic partners is a promising approach to reduce this disease.

Future study will include integrating the GMaP and BMaP supplement pilot projects into the plans for a regional implementation plan address combating this disease.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B12.
Abstract B15: An assessment of eligibility and enrollment into cancer clinical trials among a disadvantaged urban population
Authors: Ko Naomi , Caron Sarah E. , Battaglia Tracy
Published: June 2012

Background: Enrollment rates into cancer clinical trials among the adult population remains at approximately 2–11% with the vast majority being white men and women from high socioeconomic status and educational backgrounds. In order to address the unequal burden of cancer among underserved populations, it is imperative to enroll representative populations into cancer clinical trials, yet little is known about reasons why minority accrual is so low. We aim to examine the eligibility and enrollment criteria for disadvantaged populations in cancer clinical trials as a first step to increase minority accrual.

Methods: Boston Medical Center, a recently designated Minority Based Community Clinical Oncology Program by the National Cancer Institute, is the largest Safety Net medical institution in New England serving Boston's most vulnerable cancer patients. Using the hospital cancer registry to identify incident cases in the calendar year 2010 (n=1300), we conducted a retrospective review of the electronic medical record (EMR) to identify rates of screening for available cancer clinical trials. Each patient considered potentially eligible for a cancer clinical trial has documentation in their EMR from a clinical trials nurse. This screening note documents potential eligibility for enrollment, reasons for ineligibility or non-enrollment. Socio-demographic information was obtained from the cancer registry. Descriptive statistics were used to report our main outcomes: screening rate, eligibility and enrollment rate (of those screened) and reasons for not enrolling.

Results: Among 1300 newly diagnosed cancer patients served in calendar year 2010, mean age 61; 49% female; 48% White, 30% Black, 11% Hispanic, 4% Asian. One hundred clinical trials were available for accrual during the time period. Overall, we found documentation that 686 screenings for specific cancer trials were performed across 547 unique patients, resulting in a screening rate of 42% of newly diagnosed cancer patients. Among all 686 screenings, we found that patients were deemed ineligible for a specific clinical trial 92% of the time (n=630). The most commonly noted reasons for ineligibility were administrative issues (such as pending IRB approval and timing of screening) versus patient co-morbidities or disease stage. Of the patients who were deemed eligible (n=56) for clinical trials, 55% (n=31) were enrolled, of which 51% were white, 45% black and 4% Hispanic.

Conclusions: Most patients screened for a cancer clinical trial were not eligible. Earlier evaluation may address the administrative issues. Co-morbidities continue to be a major source of ineligibility for minority patients. When eligible, a racially representative sample was enrolled, suggesting the need to identify trials that are specific to our patient population in order to increase minority accrual.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B15.