bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P6-05-08: Nuclear HER3 localisation plays a role in trastuzumab resistance in HER2-positive breast cancer
Authors: Hashimoto K , Roxanis I , Generali D , Andreis D , Strina C , Cappelletti M , Macaulay V , Kong A
Published: August 2014

Background: HER3 is known to locate in the nucleus. Unlike HER4, nuclear HER3 translocation has not been reported to be due to a proteolytic cleavage process by ADAM17 and gamma-secretase. The mechanisms of nuclear HER3 induction and its role in relation to trastuzumab treatment and resistance for HER2-positive breast cancer is unclear.

Methods: Using nuclear fractionation and confocal microscopy, nuclear HER3 localisation was investigated in response to trastuzumab with or without ADAM17 inhibitor and gamma-secretase inhibitor in a panel of HER2 expressing cell lines. We also correlated nuclear HER3 expression by immunohistochemistry with treatment response in patients who underwent window trastuzumab study as well as the survival outcome in a cohort of HER2-positive breast cancer patients using Kaplan–Meier survival curves with Log-rank test.

Results: HER3 ligand heregulin and trastuzumab was found to induce nuclear HER3 translocation in HER2-positive breast cancer cell lines, including SKBR3. Nuclear HER3 was also enriched in acquired trastuzumab resistant SKBR3 cells (SKBr3-TR). Trastuzumab treatment induced several HER3 fragments and HER3100kD was found to be responsible for nuclear HER3 enrichment by fractionation. This fragment was confirmed to be a specific band of HER3 as shown by HER3 knockdown. Nuclear HER3 was reduced by inhibiting either gamma-secretase or ADAM17 inhibitor. Gamma-secretase or ADAM17 inhibitor reduced HER3100kD in both SKBr3 and SKBr3-TR cells.

In HER2-positive breast cancer patients who underwent window trastuzumab study, baseline nuclear HER3 status was not a predictor of response for trastuzumab monotherapy at day 21. However, nuclear HER3 was enriched after trastuzumab treatment in a poor-responder patient. Total HER3 expression level in cytoplasm positively was correlated with poor response to trastuzumab monotherapy in HER2-positive patients (r = 0.67, p = 0.05). There was no statistically significant difference in disease-free survival between positive and negative nuclear HER3 expression but the number of patients was small (n = 87). Further validation to assess nuclear HER3 expression as a prognostic and predictive biomarker in HER2-positive breast cancer patients undergoing trastuzumab treatment will be assessed in randomized tumour samples from FinHER study.

Conclusion: Heregulin and trastuzumab treatment seems to induce nuclear HER3 translocation in some of the HER2 positive breast cancer cells. This may be due to proteolytic cleavage of HER3 as it is reduced by ADAM17 or gamma-secretase inhibitor. Enriched nuclear localisation of HER3 seems to be one possible mechanism of acquired resistance to trastuzumab in HER2-positive breast cancer.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-08.
Abstract P6-06-16: Young age as a good prognostic factor in de novo metastatic breast cancer
Authors: Lee GE , Dawood S , Haaland BA , Tan PS , Bhoo-Pathy N , Dent RA
Published: August 2014

Background

While breast cancer is relatively rare in young women under the age of 40, its incidence is increasing and accounts for up to 40% of all female cancers. Young age at diagnosis is associated with a poorer prognosis in early breast cancers; however little is known about the natural history of young women with metastatic breast cancer. We aim to evaluate the effect of age on breast-cancer specific survival (BCS) and overall survival (OS) for patients with de novo metastatic breast cancer using data from the SEER registry.

Methods

We retrospectively analyzed 14155 patients with de novo metastatic breast cancer from the SEER registry between 2000 and 2009. Young women were defined as 50 years and below and further subdivided into three groups: 20-34, 35-39, and 40-49 years. Age 50-69 years served as a comparison group. Unadjusted overall survival (OS) and breast cancer specific survival (BCS) were accessed using Kaplan-Meier plots and compared across groups using log-rank tests. Cox proportional hazards models were then fitted to determine the association between survival end point and age after adjusting for patient and tumor characteristics.

Results

546 (3.9%) patients were age 20-34 years, 750 (5.3%) were 35-39 years, 3049 (21.5%) were 40-49 years and 9810 (69.3%) patients were 50-69 years. Median BCS among patients age 20-34, 35-39, 40-49 and 50-69 years was 30, 33, 35, 28 months respectively (P<0.0001). Median BCS among patients with estrogen receptor positive disease who were age 20-34, 35-39, 40-49 and 50-69 years was 43, 42, 51, 37 months respectively (P<0.0001). Similarly median BCS among patients with estrogen receptor negative disease who were age 20-34, 35-39, 40-49 and 50-69 years was 21, 18, 18, 17 months respectively (P<0.0001). In the multivariable model compared to patients who were age 50 -69 years those aged 20-34 years (HR 0.88, 95% CI 0.78-0.99), 35-39 years (HR 0.82, 95% CI 0.74-0.91) and 40-49 years (HR 0.84, 95% CI 0.79-0.89) had a significantly decreased risk of death from breast cancer. Similar results were obtained for OS.

Conclusion

Younger patients defined by age less than 50 years had a better BCS and OS when compared against older age group in the setting of de novo metastatic breast cancer. This may be explained by lack of important comorbidities, relatively good performance status as well as ability to tolerate more lines of chemotherapies.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-16.
Abstract P6-06-24: Intact p53 can predict more hormonal therapy benefit in invasive breast cancer: Evaluation of interactions between immunohistochemical p53 status and adjuvant therapy
Authors: Lee JW , Kim HJ , Son BH , Ahn SH
Published: August 2014

Background: To confirm the prognostic and predictive values of p53 accumulation, particularly in invasive breast cancer patients sorted according to subgroup based on immunohistochemical hormone receptor (HR) and HER2 status.

Methods: A total of 15,598 immunohistochemical data for p53, ER, PgR, and HER2 were retrospectively retrieved from the web-based database of the Korean Breast Cancer Society. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated and compared with the Kaplan-Meier method with log-rank test. Multivariate analyses were performed using a stratified Cox proportional hazard regression model. A model evaluating interactions between p53 and both hormonal therapy and chemotherapy was used to determine the treatment benefit from both modalities.

Results: Prognostic value of p53 was most significant in the HR+/HER2- subgroup for OS and BCSS, with hazard ratios of 1.44 (95% CI, 1.08-1.93) and of 1.47 (95% CI, 1.09-1.99). The hazard ratios for p53 overexpression had borderline significance in the HR+/HER2+, and were invalid in the HR-/HER2+ and HR-/HER2- subgroups. The model with interaction terms revealed that hormonal therapy significantly interacts with p53 status (p = .002 and .007 for OS and BCSS), resulting in an insignificant prognostic value of p53 status (p = .268 and .296 for OS and BCSS). An interaction between chemotherapy and p53 status was not found in this model.

Conclusion: p53 overexpression has independent prognostic value, particularly in the HR+/HER2- invasive breast cancer, which is most likely caused by differential treatment benefits from hormonal therapy depending on p53 status.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-24.
Abstract P6-06-54: Analysis of treatment and survival of pathologic occult breast cancer with axillary lymph node metastasis: Nationwide retrospective study
Authors: Sohn G , Son BH , Baek S , Lee S , Lee Y , Kim HJ , Ko BS , Yu J , Lee JW , Ahn S-H
Published: August 2014

Objective

Occult breast cancer (OBC) is a rare presentation which accounts for 0.3-1.0% of all breast cancers. In spite of limited information, there is no consensus regarding the prognostic factors and treatment of OBC. This retrospective study intends to evaluate the overall survival and prognostic factors of occult breast cancer (OBC) in Korea.

Method

This study included 142 pathologic occult breast cancer patients from January 1990 to December 2009, identified from Korean Breast Cancer Society cancer registry. All patients had pathologically positive axillary lymph node (N1-N3) along with pathologically & radiologically negative in-breast lesion (T0/Tx) based on retrospective review of database. Among 142 patients, 32 patients had only axillary lymph node dissection (ALND), 56 patients had breast conserving operation (BCO) with ALND and 54 patients had mastectomy with ALND. 96 patients (96%) had N1 disease, 23 patients (16.2%) had N2 disease and 23 patients (16.2%) had N3 disease.

Results

There was no significant statistical difference in overall survival among different operation method, which is ALND only, BCO with ALND, mastectomy with ALND (p = 0.061), considering that 12 patients (37.5%) among 32 patients who only had ALND had N3 disease comparing that only 7 (12.5%) out of 56 patients and 4 (7.4%) out of 54 patients had N3 disease in BCO with ALND and mastectomy with ALND group separately. Univariate analysis revealed that only nodal status was significant prognostic factor (p = 0.0004), and other factors including radiotherapy (p = 0.696), chemotherapy (p = 0.302), estrogen receptor positivity (p = 0.144), progesterone receptor positivity (p = 0.254), total number of removed lymph node (p = 0.586) didn't show statistical difference in overall survival.

Conclusions

This study suggests that OBC patients who only had ALND showed similar outcomes when comparing with patients who had BCO with ALND or mastectomy with ALND. Also only nodal status might be independent predictors for poor outcomes of occult breast cancer.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-54.
Abstract P6-07-07: Febrile neutropenia primary prophylaxis with granulocyte-colony stimulating factors (G-CSF) in breast cancer
Authors: Younis T , Rayson D , Skedgel C
Published: August 2014

Background: Febrile neutropenia (FN) during adjuvant chemotherapy is associated with significant morbidity, mortality risk and incremental costs. It could also lead to chemotherapy dose reductions and worse cancer outcomes. Patients who develop FN are often prescribed secondary G-CSF prophylaxis with subsequent chemotherapy cycles to decrease the risk of further episodes of infection. Practice guidelines also recommend primary G-CSF prophylaxis for: i) patients treated with chemotherapeutic regimens associated with FN risks > 20% and ii) patients treated with regimens associated with 10-20% FN risk in the presence of other patient-related factors that further increase the risk of FN. The adoption of primary G-CSF prophylaxis in clinical practice however depend on the “value for money” associated with G-CSF prophylaxis at various FN risks, where incremental cost-utility values below $100,000 per quality adjusted life year (QALY) gains are generally considered to be cost-effective. Aim: To examine the “value for money” associated with primary and secondary G-CSF prophylaxis strategies, compared with a no G-CSF strategy, for adjuvant chemotherapy in breast cancer at varying FN risks. Methods: The incremental costs and QALYs associated with G-CSF prophylaxis (primary or secondary) were examined through a decision analysis framework that incorporated i) upfront costs of G-CSF treatment (primary or secondary); ii) varying rates of baseline FN risks and iii) downstream costs and QALY gains associated with adjuvant chemotherapy based on chemotherapy dose levels (0, -1, and -2) and G-CSF prophylaxis. The primary analysis involved adjuvant TC (taxotere & cyclophosphamide) chemotherapy regimen delivered every three weeks for four cycles. Probabilities and utilities were derived from the literature, and treatment costs were based on local resources. The robustness of the model to plausible ranges of uncertainty around key parameters / assumptions was examined in sensitivity analyses. Results: Primary G-CSF prophylaxis was a cost-effective strategy compared with secondary G-CSF prophylaxis in the base case scenario. The “value for money” associated with primary G-CSF prophylaxis however was dependant on the baseline FN risk without G-CSF, and assumptions around the impact of chemotherapy dose reductions on breast cancer relapse and mortality. Two way sensitivity analyses illustrated plausible combinations of baseline FN risks and detrimental impact of reduced chemotherapy dose associated with favorable value for money. Conclusions: Primary G-CSF prophylaxis overall appears to be a cost-effective strategy for patients at high FN risk. The FN threshold at which primary G-CSF is associated with good value for money is however dependent on the potential detrimental impact of reduced chemotherapy dose on breast cancer outcomes.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-07-07.
Abstract P6-08-02: Quality of life in breast cancer patients after breast conservation surgery or modified radical mastectomy - A comparative study from a tertiary cancer care center in India
Authors: Pudumjee SB , Mane AD , Deshmukh SP , Bokil KP , Choudhary AG , Sane SP
Published: August 2014

Background: The research in QOL of breast cancer patients has been predominantly focussed on the western world and has yielded mixed results. However there is a paucity of QOL data in Indian patients. Due to increasing incidence of breast cancer in the Indian population, it is imperative to look into the QOL experienced by patients after treatment.

Aim: The aim of the study was to assess any difference in QOL experienced by women having undergone Breast Conservation Surgery (BCS) and by those having undergone a Modified Radical Mastectomy (MRM) in a tertiary cancer care center.

Methodology: Total 75 patients were assessed prospectively (MRM = 43, BCS = 32) using the Functional Assessment of Cancer Therapy - Breast (FACT - B) Version 4 scale. Patients diagnosed with Stage I, II or III breast cancers were assessed after 6 months post completion of all treatment.

Results: The Mann Whitney - U test showed that the overall QOL did not differ significantly across the two groups but the FACT - G (General) and Functional Well Being (FWB) subscale showed that BCS patients fared better than those of MRM with P-values of 0.033 and 0.031 respectively(Table 1). MRM patients did not experience significantly lower body image and decreased sexual functioning when compared to the BCS patients.

Conclusions: There was no significant difference between the QOL experienced by patients of MRM and BCS. However BCS patients did report higher levels of functionality as well as general QOL without considering factors specific to breast cancer. The lack of difference between body image and sexual functioning was in sharp contrast to the findings in western literature and can be explained by the cultural variance.

Implications: This study will serve the purpose of establishing the need for further culturally appropriate investigations into QOL of breast cancer patients as well as lend impetus to more targeted, culture appropriate forms of psychosocial intervention.

Difference between QOL for BCS and MRM patients BCS (Median)MRM (median)P-valuePhysical Well Being25.5240.088Social Well Being25.435240.266Emotional Well Being23200.188Functional Well Being27.5250.031*Breast Cancer Subscale26.5270.855Trial Outcome Index78730.133FACT - G99.5910.033*FACT - B124.51170.065*significant at the 0.05 level

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-08-02.
Abstract P6-09-01: Central Ki67 analysis as a predictor for adjuvant capecitabine efficacy in early breast cancer (EBC) subtypes in US oncology trial 01062
Authors: O'Shaughnessy J , Koeppen H , Crockett M , Lackner M , Spoerke JM , Wilson T , Levin MK , Pippen J , Paul D , Stokoe C , Blum J , Holmes FA , Lindquist DL , Krekow L , Vukelja SJ , Sedlacek S , Rivera R , Brooks RJ , McIntyre KJ , Schwartz JE , Jones S
Published: August 2014

Background: USON 01062 (O’Shaughnessy J, et al. Proc SABCS, 2010, abst S4-2) showed no improvement in the primary endpoint of disease-free survival (DFS) (median FU 5 yrs: HR 0.84, 95% CI: 0.67-1.05; p = 0.125) with the addition of capecitabine (X) to standard adjuvant chemotherapy, but showed improvement in OS (HR 0.68, 95% CI: 0.51-0.92; p = 0.011). Exploratory analysis of local pathology-assessed Ki67 suggested benefit from adjuvant X in pts with more highly proliferative cancers with Ki67 ≥ 10% (Pippen J et al. Proc ASCO, 2011, abst 500). The objective of this study is to determine whether centrally-performed Ki67 IHC results corroborate or refute this finding.

Methods: 2610 pts with resected high risk EBC were randomized to receive 4 cycles of AC (doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2) IV every 3 wks for 4 cycles followed by either docetaxel 100mg/m2 IV or docetaxel 75mg/m2 IV plus X 825mg/m2 PO bid for 14 days every 3 wks for 4 cycles. Archival primary breast cancer tissue was collected on 2000 pts for predictive biomarker analyses. Central Ki67 IHC was performed using the anti-Ki67 monoclonal antibody SP6 and was read by one pathologist (HK) according to published recommendations (Dowsett M, et al. JNCI 103:1-9, 2011).

Results: Central Ki67 IHC has been performed on 1440 pts who had centrally-validated informed consents. The distribution of% Ki67-positive cells by locally-assessed ER/HER2 subtype is shown below. 45% of HR+ HER2- BCs had a Ki67 ≤ 10%, while 24% had a Ki67 11% to 20%, and 31% had a Ki67 > 20%. The concordance between the local vs central Ki67 results was low at 46% for Ki67 <10%, 49% for Ki67 10%-20%, and 76% for Ki67 > 20%. The central Ki67 results tended to be higher than the local testing results. Central mRNA classifiers were developed for ER, PR, HER2 and Ki67 using Fluidigm Microfluidics Dynamic Arrays and correlate highly with central IHC assessment of these markers.

Conclusions: HR+ HER2- EBC is enriched for cancers with a low proliferative rate, a group of pts unlikely to benefit from the cell cycle-specific cytotoxic agent, capecitabine. Analyses of the impact of adjuvant X added to AC/T in EBC pts according to ER status, and according to Ki67 (analyzed as a binary and continuous variable) will be performed prior to SABCS, 2013.

Number of Patients% Ki67 Pos CellsTotal *HR+TNHER2+/HR+HER2+/ HR-0-104163622222711-151391066151016-20126871615821-3018411539201031-1005751403423555Total144081042510790*Totals do not equal sum of subtype categories due to missing HER2 information

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-01.
Abstract PD4-6: Combined analysis of gene expression, DNA copy number and mutation profiling data to display biological process anomalies in individual cancers
Authors: Shi W , Balazs B , Qi Y , Györffy B , Wang B , Liu C-G , Shiang CY , Valero V , Moulder-Thompson S , Avritscher R , Powis G , Hortobagyi GN , Natowicz R , Wali V , Weinstein J , Symmans WF , Pusztai L
Published: August 2014

Background: The goal of this analysis was to develop a computational tool that integrates gene expression, DNA copy number and sequence abnormalities in individual cancers in the framework of biological processes.

Methods and Findings: We used the hierarchical structure of the Gene Ontology (GO) database to create a reference network and projected mRNA expression, DNA copy number and mutation anomalies detected in single samples into this space. We applied our method to 59 breast cancers where all three types of molecular data were available. Each cancer had a large number of disturbed biological processes. Locomotion, multicellular organismal process and signal transduction pathways were the most commonly affected GO terms but the individual molecular events were different from case-to-case. Estrogen receptor-positive and -negative cancers had different repertoire of anomalies. We tested the functional impact of 27 mRNAs that had overexpression in cancer with variable frequency (<2-42%) using an siRNA screen. Each of these genes inhibited cell growth in at least some of 18 breast cancer cell lines.

Conclusions We developed a free, on-line software tool (http://netgoplot.org) to display the complex genomic abnormalities in individual cancers in the biological framework of the GO biological processes. We show that each cancer harbors a large number and unique combination of pathway anomalies, the individual molecular events that underlie the pathway level disturbances vary from case-to-case. Our in vitro experiments indicate that even rare case-specific molecular abnormalities can play a functional role and driver events may vary from case to case depending on the constellation of other molecular anomalies.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD4-6.
Abstract PD6-7: The prognostic relevance of disseminated tumor cells (DTC) form the bone marrow (BM) in different molecular subtypes of primary breast cancer (PBC) patients
Authors: Hartkopf AD , Taran F-A , Brucker S , Hahn M , Wallwiener D , Becker S , Solomayer E-F , Wallwiener M , Fehm T
Published: August 2014

Background:

The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (PBC) patients is associated with a worsened prognosis. This is the largest single-center study that determines the impact of DTC on disease free (DFS) and overall survival and compares it to predefined molecular subtypes of PBC.

Methods:

BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany between 01/2001 and 01/2013. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HR+/HER2-), (2) HER2-positive (HER2+), and (3) HR-negative/HER2-negative (HR-/HER2-) patients. The DTC-status was compared to other prognostic factors by use of the chi-squared test and survival was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression).

Results:

3,141 patients were available for this retrospective analysis. Of these 803 (26%) were DTC-positive. DTC-positivity was associated with larger tumors (p<0.001), positive lymph nodes (p = 0.001), ER-negative (p = 0.016) and PR-negative (p<0.001) patients. DTC-positive patients were at an increased risk of death (median OS of DTC- vs. DTC+ patients: n. r. (not reached) vs. 115 (95% CI: 113-118) months, p = 0.004) and disease relapse (median DFS was n. r. in either groups, p<0.001). Independent factors for OS / DFS were DTC-status, menopausal-status, tumor size, nodal-status, ER-status and PR-status / DTC-status, tumor size, nodal-status and ER-status. In the subgroup analysis (median OS was n. r. in either groups), the DTC-status had a significant impact on OS only within the HR+/HER2- subgroup (p = 0.004) and on DFS in the HR+/HER2- (p = 0.005) and the HER2+ subgroup (p<0.001).

Conclusion:

This study confirms the strong and independent prognostic value of DTC-determination in primary breast cancer patients. With respect to analysis of different molecular subtypes, the DTC-status was found to be of prognostic significance especially in HR+/HER2- patients. The DTC-status might help to identify HR+/HER2- patients that are at an increased risk of death or disease relapse and thus in need for an aggressive adjuvant treatment.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-7.
Abstract PD6-8: Prognostic value of disseminated tumor cells according to ER/PR and HER2 status in non-metastatic breast cancer
Authors: Lee JS , Magbanua MJM , Moore AP , Esserman LJ , Park JW
Published: August 2014

Background: Disseminated tumor cells (DTCs) in the bone marrow from breast cancer patients have been reported as a prognostic factor. We evaluated prognostic value of DTCs in non-metastatic breast cancer according to ER/PR and HER2 status.

Methods: Bone marrow aspirates were obtained from 607 non-metastatic breast cancer patients at the time of primary surgery between 1999 and 2012. DTCs were identified via immunomagnetic enrichment followed by flow cytometry (IE/FC) using anti-EpCAM monoclonal antibody (mAb). The relation between high DTC count and clinical outcome was analyzed with ER/PR and HER2 status. Patients whose DTC count is in the above 80th percentile were considered as higher DTCs.

Results: Median and mean DTC count were 7.2 and 24.5 cells/mL and 80th percentile was 18.5 cells/mL. Higher DTC group (> = 18.5 cells/mL) showed impaired disease free survival (DFS; P = .019, log-rank) after median follow-up of 59 months. This poorer outcome in higher DTC group was observed mainly in ER(-) patients and triple negative patients with lower DFS (P = .002 and 018) and overall survival (OS; P = .004 and .012). There was no significant survival difference in ER(+), HER2(+), or ER(+)/HER2(-) patients.

Conclusion: High DTCs in non-metastatic breast cancer is associated with poor clinical outcome, especially in ER(-) or triple negative patients. However, DTCs is not related with prognosis in other ER/HER2 status groups.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-8.
Abstract S6-07: Genomic characterisation of metastatic samples from breast cancer patients using next generation sequencing
Authors: Bachelot T , Lefebvre C , Campone M , Levy C , Arnedos M , Bonnefoi H , Dieras V , Treilleux I , Goncalves A , Clapisson G , Jimenez M , Andre F
Published: August 2014

Background: Although several studies have reported genomic characterisation of primary breast tumors, little is known about the genomic alterations of the metastatic tissues. Breast cancer patients who were prospectively enrolled in a trial (SAFIR01) underwent a biopsy of metastasis. The primary aim of this biopsy was to drive the treatment according to the results of whole genome CGH arrays and sanger sequencing on two genes (PIK3CA and AKT1). The results of the clinical trial were previously reported (André et al ASCO 2013). The secondary goal of the biopsies was to perform genomic characterisation of metastases in breast cancer patients. Here we report the analyses of such metastatic samples using next generation sequencing (NGS) approaches.

Patients and methods: Two approaches were applied. In order to describe the incidence of targetable genomic alterations, we performed in depth targeted sequencing on 100 genes (200x coverage) using Illumina HiSeq 2000 (DNA vision). This analysis was performed on 240 metastatic samples. The second approach was more exploratory and aimed at discovering new genes involved in the metastatic process and/or resistance to therapies. In order to achieve this goal, we performed whole exome sequencing in 100 pairs of metastatic tissue (100x) and normal DNA (Integragen Inc, Hiseq platform). Finally, phosphor-S6K staining was performed in 300 samples in order to explore the activation status of mTOR pathway in metastatic disease, and to correlate with genomic data.

Results: Targeted sequencing was performed on 240 metastatic samples in order to report the prevalence of targetable genomic alterations in metastatic breast cancer. Results are available for the first 159 samples. In addition to the already reported PIK3CA (26%) and AKT1 mutations (4%), NGS identified mutations of PTEN (4%), ERBB2 (2%), K-Ras (1%), ATM (2%), CDH1 (2%), GATA3 (2%), PTPN11 (1%), PTPRD (1%), ROS1 (1%). Results on the 81 samples, together with whole exome sequencing (n = 100) and phosphoproteins are being analysed and results will be available mid-november 2013.

Conclusion: This is the first large study that aims at defining the genomic landscape of metastatic samples. Results will provide insights into the prevalence of targetable genomic alterations in metastatic tissue, together with candidate genes involved in the metastatic process and resistance to therapies.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-07.
Abstract A16: Promoting colorectal cancer screening in urban, minority populations with community health workers.
Authors: Sanchez Martha , Ashby-Thompson Maxine , Jacobson Judith S. , Hepburn Patricia , Grann Victor E.
Published: August 2014

Background: Colorectal cancer (CRC) is the third most common cancer and cause of cancer-related death in the United States. Screening prevents not only mortality but also the occurrence of CRC. Our group reaches out to and educates members of our predominantly low-income Hispanic and African American community about cancer treatment, research, and prevention by establishing partnerships with community-based organizations (CBOs) and training community health workers (CHWs). In 2010, we learned that relatively few CBO clients had been screened or intended to be screened for CRC, and that the CHWs also were not well informed about CRC.

Methods: We developed an enhanced training program about CRC for CHWs and their clients. We renewed two of our CBO partnerships, added one more, retrained some previously trained CHWs, and recruited and trained CHWs from the new CBO. We developed a new pre- and post-training 10-question instrument to evaluate what the CHWs already knew and what they learned from our training. We compared the CHWs' average scores (proportions of correct answers) before and after the training. Further training was conducted to reinforce CHWs' knowledge. Using focus groups and community-based participatory research methods with the CHWs, we then developed two educational interventions that the CHWs will implement in the coming months.

Results: Fifteen CHWs were trained or retrained. Most of the participating CHWs had previously received our training. All of them answered at least 6 of the 10 questions correctly both before and after the training, but average scores improved from 75% correct before the training to 82% correct afterwards.

Next steps: Each CHW will educate 20 clients (n=300) aged 50+ years about CRC screening and attempt to schedule them for screening. In the two intervention groups, we will compare proportions of clients who receive CRC screening. Results will be disseminated to the community in our quarterly community newsletter, a report to the CBOs, and a press release to the local media.

Citation Format: Martha Sanchez, Maxine Ashby-Thompson, Judith S. Jacobson, Patricia Hepburn, Victor E. Grann. Promoting colorectal cancer screening in urban, minority populations with community health workers. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A16.
Abstract A32: Do theoretical mediators differentiate adherent and nonadherent American Indian mammographic screeners? Preliminary results from one tribe.
Authors: Petersen Wesley , Nicometo Ann M.
Published: August 2014

Purpose: The study purpose is to learn whether theoretical mediators (Planned Behavior/Reasoned Action, Social Norms, Social Support, Social Networks, Health Beliefs, Health Literacy) can be used to distinguished American Indian women who are adherent with Indian Health Service (IHS) mammographic screening guidelines from those who are not adherent with these guidelines. Women in the Bemidji Area of the Indian Health Service have mammographic screening rates much lower than the IHS average for all IHS areas. Bemidji Area women are diagnosed at later stage and have higher mortality than is seen in the overall IHS. Our ultimate goal is to develop interventions to increase adherence among non-adherent screeners. Experimental procedures: In phase one, we have identified 64 women for interviews. Based on women's risk factors and screening histories, women were assigned to one of four groups: high risk/adherent, low risk/adherent, high risk/non-adherent, and low risk/non-adherent. Our goal is to have 16 women in each group. Currently, we have interviewed and conducted preliminary analysis of 19 women (4 higher risk/ adherent; 7 lower risk/non-adherent, 4 higher risk, non-adherent, 4 lower risk/adherent). Interview responses have been coded for themes, then categorized and descriptively quantified. Preliminary results: Adherent and non-adherent mammographic screeners can be differentiated by: 1) Theory of Planned Behavior (personal attitudes toward screening; perceived attitudes of family/friends and tribe toward annual screening; and past screening behavior). 2) Social Norms (perceptions of general health of respondents, family/friends, and tribe; health behaviors; barriers to screening; influences on attitudes and behaviors; healthy behaviors; health values; perceptions of common cancers among tribal members and women; the mammography experience; and influential members within social networks). 3) Social Support (emotional support for worry and fear and companionship. 4) Health Beliefs (susceptibility and severity of cancer). In other regards, these mediators and Health Literacy do not distinguish between adherent and non-adherent screeners. Conclusions: Theoretical mediators may be a useful way to distinguish between adherent and non-adherent screeners and point to potential avenues to intervene in the non-adherent population of American Indian women.

Citation Format: Wesley Petersen, Ann M. Nicometo. Do theoretical mediators differentiate adherent and nonadherent American Indian mammographic screeners? Preliminary results from one tribe. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A32.
Abstract A37: Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers.
Authors: Olivos David J. , Saunders Mary R. , Li Yuanpei , Awwad Nasir Al , Lam Kit S.
Published: August 2014

Luteinizing hormone releasing hormone receptors (LHRHR) are overexpressed on cancer cell surfaces of the prostate, ovary, breast, and cervix'each of which reflect a health disparity in the African American, Latino, and Asian communities. Chemotherapy in combination with surgery, radiation, and hormone therapy is commonly used to treat these cancer types. Novel LHRH analogues have been discovered and optimized to selectively deliver cytotoxic agents to the tumor mass as a means to improve therapeutic index and efficacy while sparing normal tissues. We have synthesized several generations of 20% down-substituted One Bead One Compound (OBOC) focused libraries composed of select D- and L- amino acids, carboxylic acids, sulfonyls, and isocyanates, and screened under highly stringent conditions against LHRHR positive, negative, and overexpressing cell lines. Our novel LHRH analogues out performed clinical LHRH analogues [d-Trp6] LHRH and [d-Lys6] LHRH in binding affinity against LHRHR in vitro. Cell adhesion ligands for prostate (PC3N, PC3M), breast (MDA MB-231, MCF7), ovarian (A2780), and cervical cancer (HeLa, SiHa) have been discovered, and their use as tumor-homing agents for diagnostic and therapeutic purposes is being explored in xenograph models. Our preliminary studies utilizing our docetaxel loaded disulfide cross-linked nanoparticle platform demonstrate a therapeutic efficacy against PC3M-luc subcutaneous xenograft. We believe these drug loaded nanocarriers will be able to target and kill cancer cells more efficiently while minimizing side effects compared to current treatments when decorated with our highly specific and high affinity LHRH ligands. This approach is a promising strategy for future clinical development.

Citation Format: David J. Olivos, III, Mary R. Saunders, Yuanpei Li, Nasir Al Awwad, Kit S. Lam. Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A37.
Abstract A61: Characterizing inflammatory breast cancer among Arab Americans in the California, Detroit, and New Jersey Surveillance, Epidemiology and End Results (SEER) registries (1988-2008).
Authors: Hirko Kelly A. , Soliman Amr S. , Banerjee Mousumi , Ruterbusch Julie , Harford Joe B. , Chamberlain Robert , Graff Jon J. , Merajver Sofia D. , Schwartz Kendra
Published: August 2014

Introduction: Inflammatory breast cancer (IBC) is characterized by an apparent geographical distribution in incidence, being more common in North Africa than other parts of the world. Despite the rapid growth of immigrants to the United States from Arab nations, because a racial category is rarely appropriated for this group, little is known about disease patterns among Arab Americans. The aim of this study was to describe the proportion of IBC among different racial groups, including Arab Americans from the Detroit, New Jersey and California Surveillance, Epidemiology and End Results (SEER) registries.

Methods: We utilized a validated Arab surname algorithm to identify women of Arab descent from the SEER registries. Differences in the proportion of IBC out of all breast cancer and IBC characteristics by race and menopausal status were evaluated using chi-square tests for categorical variables, t-tests and ANOVA tests for continuous variables, and log-rank tests for survival data. We modeled the association between race and IBC among all women with breast cancer using hierarchical logistic regression models, adjusting for individual and county-level variables.

Results: Statistically significant differences in the proportion of IBC out of all breast cancers by race were evident. In a hierarchical model, adjusting for age, estrogen and progesterone receptor, human epidermal growth receptor 2, registry and county-level socioeconomic position, Arab-Americans (OR=1.5, 95% CI=1.2,1.9), Hispanics (OR=1.2, 95% CI=1.1,1.3), Non-Hispanic Blacks (OR=1.3, 95% CI=1.2, 1.4), and American Indians/Alaskans (OR=1.9, 95% CI=1.1, 3.4) had increased odds of IBC, while Asians had decreased odds of IBC as compared to Non-Hispanic Whites (OR=0.6, 95% CI=0.6, 0.7).

Conclusions: IBC may be more common among certain minority groups, including Arab American women. Understanding the descriptive epidemiology of IBC by race may generate hypotheses about risk factors for this aggressive disease. Future research should focus on etiologic factors that may explain these differences.

Citation Format: Kelly A. Hirko, Amr S. Soliman, Mousumi Banerjee, Julie Ruterbusch, Joe B. Harford, Robert Chamberlain, Jon J. Graff, Sofia D. Merajver, Kendra Schwartz. Characterizing inflammatory breast cancer among Arab Americans in the California, Detroit, and New Jersey Surveillance, Epidemiology and End Results (SEER) registries (1988-2008). [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A61.
Abstract A89: Do patient tracking, follow up, and referral practices contribute to breast cancer disparities in a large urban area?
Authors: Weldon Christine B. , Knight Jimmie , Trosman Julia R. , Dupuy Danielle , Broggenkamp Betty , Schink Julian C. , Orsi Jennifer M. , Murphy Anne Marie
Published: August 2014

Background: Chicago Black women are 62% more likely to die from breast (BC) cancer than White women. Previous data from 39 Chicago hospitals suggested significant quality deficits in breast cancer screening and treatment (Chicago Breast Cancer Quality Consortium, 2010). Patient tracking, follow up and referral practices may influence quality of care for minority women (Mojica et al, Cancer Control, 2007). Our goal is to evaluate tracking, follow up and referral practices during screening, diagnosis and treatment of BC at Chicago hospitals servicing Black women.

Methods: Using the framework approach of qualitative research, we conducted interviews with providers of BC screening and care from 20 Chicago institutions with Black patients averaging 50% of patient base (15 community, 3 academic and 2 public hospitals). Informants included surgeons, medical oncologists, radiologists, mammography technicians, internists, nurses, administrators, and patient navigators. Interviews were transcribed, and thematic and statistical analyses were performed (simple frequencies and Fisher's exact test).

Results: Six of the 20 sites (30%) follow up with patients who did not show for a scheduled mammography visit. Five of these sites (83%, 5/6) have a low “no-show” rate (below 20%), compared to 4 sites (29%, 4/14) with low “no-show” rates among the 14 sites without follow-up (p=0.05). Seven of the 20 sites (35%) direct diagnosed patients to their next step in care by providing referrals and guidance, while other 13 sites rely on a primary care physician or leave the patient without a clear care plan. BC patients at 6 of the 7 sites directing care (86%, 6/7) are referred to a mid- or high-volume surgeon (3+ BC surgeries / month), compared to patients from only 1 of the 13 sites not directing care (p=0.001). Nine of the 20 sites track diagnosed BC patients through their care. Five of them (56%, 5/9) also track survivors, compared to none (0%, 0/11) of the 11 sites who do not track patients (p=0.008).

Conclusions: Poor tracking, follow up and referral practices for breast cancer screening and treatment are associated with suboptimal care and may contribute to outcome disparities for Black women in Chicago.

Citation Format: Christine B. WeldonJimmie Knight, III, Julia R. Trosman, Danielle Dupuy, Betty Broggenkamp, Julian C. Schink, Jennifer M. Orsi, Anne Marie Murphy. Do patient tracking, follow up, and referral practices contribute to breast cancer disparities in a large urban area? [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A89.
Abstract B02: Promotores advancing knowledge and participation in cancer research studies.
Authors: Cupertino Ana Paula , Rios Johana Bravo De los , Saint-Elin Mercedes
Published: August 2014

Background and Purpose: Less than three percent of all adult cancer patients participate in cancer research studies. Participation is even lower for patients from underserved Latino populations. Community Health Workers (Promotores de Salud) have been shown to improve minority participation in clinical research and access to care. The objective is to describe the development and implementation of a theory-based, language and literacy appropriate training program to advance awareness and interest in cancer research studies among Latinos. Our central hypothesis is that a culturally sensitive, language and literacy appropriate program will improve a) knowledge about cancer research studies and b) attitudes regarding participation. Study Design: The study was carried out in three phases: 1) Building an infrastructure for a commu nity based participatory research program; 2) Training promotores utilizing a community-based curriculum; and 3) Using Paulo Freire's education model, we designed and implemented a cancer 101 and a cancer research studies training program. Prior to the training, Latino community members completed a pre-assessment that included demographic, socio-economic information, and open ended questions about cancer topics and cancer research studies. Results: A total of 27 Promotores enrolled in the training program and 22 (81.48%) completed the three sessions. At the end of the training session, 92% believed that it was very important for community members to learn about cancer research studies and 85% felt comfortable talking about cancer research studies in their communities. Impact: Our study demonstrated the feasibility of recruiting and engaging promotores to improve community knowledge of cancer research studies and attitudes regarding participation in cancer research studies. This initial step will inform the development of future community-based interventions.

Citation Format: Ana Paula Cupertino, Johana Bravo De los Rios, Mercedes Saint-Elin. Promotores advancing knowledge and participation in cancer research studies. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B02.
Abstract B52: Polymorphisms in the metabolism-related genes and obesity may explain prostate cancer disparity in African American men.
Authors: Chornokur Ganna , Amankwah Ernest , Park Jong , Phelan Catherine , Kumar Nagi
Published: August 2014

Background. Prostate cancer (PCa) racial disparity is likely to be multifactorial, involving the individual's genotype, the environment and their interaction. We investigated the association between selected functional polymorphisms in the metabolism-related genes and the risk of PCa in African American/ Black and Non-Hispanic White men. We further explored if these associations varied by body mass index (BMI) in the two races.

Methods. DNA samples from 259 (136 cases and 123 controls) Black and 269 (147 cases and 142 controls) White men, matched by age, Gleason score and PSA were genotyped for 10 selected single nucleotide polymorphisms (SNPs) in 7 metabolism related genes using the TaqMan PCR. The dominant, recessive and additive age-adjusted unconditional logistic regression models were fitted for all men combined, for each race and stratified by BMI, height and smoking habits within each race.

Results. Three SNPs showed statistically significant associations with PCa. In Black men: rs7501939 (OR=2.42; CI 1.31-4.47; p=0.0046) and rs4430796 (OR=0.57; CI 0.34-0.97; p=0.0383), both in the HNF1B/ TCF2 gene and associated with diabetes. In White men: rs4962416 (OR=1.52; CI 1.02-2.26; p=0.0384) in the CTBP2 gene. In addition, BMI in Black men (OR=1.06; CI 1.008-1.114; p=0.022), and height in White men (OR=0.92; CI 0.85-0.99; p=0.0434) showed significant associations. Interestingly, rs7501939 in the HNF1B gene was associated with PCa exclusively in obese Black men (OR=2.14; CI 1.2-3.8; p=0.0103).

Conclusions. Our results suggest that polymorphisms in the metabolism related genes may be involved in PCa disparity, possibly through the mechanism of obesity-related hormonal shift and disrupted androgen signaling. We are planning a well-powered study to test this hypothesis.

Citation Format: Ganna Chornokur, Ernest Amankwah, Jong Park, Catherine Phelan, Nagi Kumar. Polymorphisms in the metabolism-related genes and obesity may explain prostate cancer disparity in African American men. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B52.