bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-09-08: Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence
Authors: White AJ , Bradshaw PT , Herring AH , Teitelbaum SL , Beyea J , Stellman SD , Steck SE , Mordukhovich I , Eng SM , Engel LS , Conway K , Hatch M , Neugut AI , Santella RM , Gammon MD 
Published: May 2016

Abstract
Background. Previous epidemiologic studies, including our own, have consistently linked long-term exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to increased breast cancer incidence. It is unclear whether single sources, specific groups, or all PAH sources should be targeted for breast cancer risk reduction. This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures.
Methods. In a population-based case-control study conducted on Long Island, New York (N=1,508 breast cancer cases/1,556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake.
Results. Most women were exposed to PAHs from multiple sources. In a hierarchical model, breast cancer incidence was positively associated with ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.42) and residential synthetic firelog burning (OR=1.30, 95%CrI=1.06, 1.60). Additionally, PAH exposure groups, including ingestion (OR=1.45, 95%CrI=1.16, 1.79), indoor stove/fireplace use (OR=1.30, 95%CrI=1.02, 1.62), and total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.46, 95%CrI=1.03, 2.05), were associated with increased breast cancer incidence.
Conclusions. Groups of PAH sources, especially those for ingestion and indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor.
Citation Format: White AJ, Bradshaw PT, Herring AH, Teitelbaum SL, Beyea J, Stellman SD, Steck SE, Mordukhovich I, Eng SM, Engel LS, Conway K, Hatch M, Neugut AI, Santella RM, Gammon MD. Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-08.
Abstract P6-10-02: Patient rather than physician-related barriers to tamoxifen uptake for breast cancer prevention in high-risk women
Authors: Skandarajah AR , Thomas S , Chin-Lenn L , Mann B , Lindeman G 
Published: May 2016

Abstract
Background: Tamoxifen use for 5 years confers 35% risk reduction in breast cancer at 15 years, although the evidence to support its use for BRCA1 or BRCA2 mutation carriers is less clear. Since 2014, it has been our policy to discuss and recommend endocrine prevention to every eligible individual who attends the risk management clinic (for gene carriers or women with a strong family history) at our institution.
Aim: To assess the uptake of endocrine prevention in a high risk population when uniformly recommended and reasons for declining prevention.
Methods: All patients attending risk management clinic between February 2014 until May, 2015 received both verbal and written evidence-based information on endocrine prevention and were registered prospectively. Endocrine prevention use and cessation was captured. Reasons for declining or ineligibility for tamoxifen use were recorded.
Results: During the study period, 314 consultations were carried out on 248 women. They comprised 38 BRCA1 and 42 BRCA2 mutation carriers, 4 Peutz-Jegher syndrome patients, 155 women with strong family history, 9 with moderate family history. Their median age was 39.7 (range: 21-70 years). Despite routine policy, Tamoxifen prevention was routinely discussed, except where a patient required biopsy or was given biopsy results n=14 (7%). One patient had a new cancer diagnosis during this period. In 52 women, tamoxifen was not recommended for the following reasons: patients re-assessed as moderate risk (9), on other prevention trials (2), very young/old age (28), pregnant or breast-feeding (10) and previous mastectomy/cancer/DCIS (3). Of the remaining 182 eligible patients, 14 (8%) were on tamoxifen (median duration 12 months, range= 1-20 months), 8 (4%) had ceased tamoxifen due to side effects. Main reasons for declining were 25 (14%) were trying to conceive, 34 (19%) prefer prophylactic mastectomy, 15 (8%) were concerned regarding the side effects, 5 (3%) were currently suffering from menopause and 4 (2%) wished to await salpingo-oophorectomy. 66 (36%) indicated that they were ‘not interested’.
Conclusions: Physician-reluctance is not the reason for poor uptake of endocrine prevention in a specialized risk management clinic. Contraindications are common, many women elect for alternative risk reducing strategies and despite supportive evidence, many women prefer to choose surveillance alone over medical prevention.
Citation Format: Skandarajah AR, Thomas S, Chin-Lenn L, Mann B, Lindeman G. Patient rather than physician-related barriers to tamoxifen uptake for breast cancer prevention in high-risk women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-02.
Abstract P6-12-05: Impact of the Middle East unrest on management of breast cancer – A single institution experience
Authors: Khalifa A , Abdul-Hadi M , Al-Haddad H , Abu-Rida L 
Published: May 2016

Abstract
King Fahad University Hospital of Dammam (KFHU) is a major referral teaching Hospital in the Eastern province in Saudi Arabia. With permission, The Breast Division at KFHU accepts expatriate patients for treatment of breast cancer free of charge. Between Jan 2010 and June 2015 the unit has received 435 new and previously treated breast cancer patients, 35% of them were expatiates. We have noticed that most of these patients had an out of their hand delay in initiating either their investigations for a breast lump or start of active treatment; this has resulted in less than optimum prognosis in many cases. We reported that 75% of these patients had an average of 6-19 months delay before they presented for investigations of a breast mass, 25% had received previous irregular treatment and did not complete their management due to war unrest and travelling. More than 70% of patients who needed radiotherapy did not receive it due to unavailability of treatment facility. Conclusion: In spite of the dramatic improvement in diagnosing early breast cancer, after the wide spread of screening programs in the last decade, we are faced again with recent increase in advanced presentations and poor outcome due to war unrest. With the expected increase in the number of similar cases we think that this category of patients should be addressed as a special category.
Citation Format: Khalifa A, Abdul-Hadi M, Al-Haddad H, Abu-Rida L. Impact of the Middle East unrest on management of breast cancer – A single institution experience. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-05.
Abstract P6-12-06: Preoperative chemotherapy regimens and breast cancer subtype in an underinsured Hispanic population
Authors: Mehta D , Winton L , Walters J , Hsu C-H , Nodora J , Martinez ME , Bouton M , Komenaka IK 
Published: May 2016

Abstract
Background: Although the Hispanic population is among the fastest growing in the United States, however, less is known about them then other populations. Breast cancer in different racial/ethnic populations display different behaviors. The current study was performed to examine response to preoperative chemotherapy regimen and by breast cancer subtype in a Hispanic safety net population.
Methods: A retrospective review of Hispanic breast cancer patients who underwent preoperative chemotherapy from July 2001 to February May 2015 at a safety net hospital. Sociodemographic, clinical, and treatment variables were evaluated. Response to chemotherapy regimen was recorded. Breast cancer subtypes were divided based on IHC and FISH testing. Luminal B subtype was classified based on Ki67 (&gt;15%) and PR (&lt;20%).
Results: The average age of the 133 patients was 45 years. 93% of the patients were insured with Medicaid or uninsured (70%). The average size of the cancers at presentation was 5cm. Overall 86% of patients had a clinical response to preoperative chemotherapy and 35% had pathologic complete response (pCR). AC and TC regimens had the lowest rate of pCR at 16%. AC/T (every 3 week and weekly) had similar rates of pCR 23% and 29%, while dose dense regimens showed pCR 40%. Herceptin containing regimens had pCR 57%. 7 patients received TAC and 71% had pCR.
By subtype, Luminal A and B patients had low rates of pCR 9% and 14% respectively. Luminal B patients did benefit from preoperative chemotherapy as 86% of patients who were not candidates for breast conservation at presentation were able to undergo lumpectomy after preoperative chemotherapy. Her2 subtype patients who got Herceptin had pCR 57%. Triple negative patients had pCR 54%.
Conclusions: In this underinsured, Hispanic population who presented at advanced stages, differences in response to preoperative chemotherapy were seen based on breast cancer subtype. Differences were also seen based on chemotherapy regimen. TAC maybe a particularly effective regimen in triple negative Hispanic women.
Citation Format: Mehta D, Winton L, Walters J, Hsu C-H, Nodora J, Martinez ME, Bouton M, Komenaka IK. Preoperative chemotherapy regimens and breast cancer subtype in an underinsured Hispanic population. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-06.
Abstract P6-12-13: Awareness and acceptability of skin application of preventive medications for breast cancer
Authors: Karavites LC , Allu S , Khan SA , Kaiser K 
Published: May 2016

Abstract
OBJECTIVE: To better understand women's knowledge and perceptions of breast cancer prevention medications and determine if a topical administration of these medications would increase acceptability.
METHODS: Focus groups were conducted with healthy women identified through the breast center of a single institution. An experienced moderator led participants through a discussion of breast cancer risk perceptions, knowledge of and concerns about risk reduction medications, and their views of a skin application of risk reducing medication. Participants provided sociodemographic information, breast cancer risk factors, and prior physician recommendations to take risk-reducing medicines. Trained research personnel examined all qualitative results systematically. Participants' breast cancer risk was estimated using the Gail Model.
RESULTS: Four focus groups (N=32) were conducted. Most participants had at least a college degree (78.2%) and were of either European (50%) or African ancestry (31%). The majority (72%) were at elevated risk for breast cancer, just over half of these women perceived themselves to be at higher than average risk. Only 19% of participants had prior knowledge of preventive medications. Women who perceived themselves to be at high risk were more likely to know about preventive medications than those who did not, 38% vs 0% respectively. Over 90% of the focus group participants stated that they would prefer a topical application of a preventive medication to a pill if their physician advised them to take preventive medication.
CONCLUSION: Awareness of preventive medications was low even in a highly educated sample of high-risk women. If given a choice in the route of administration of chemoprevention, nine out of ten women preferred a gel to a pill. Future work should focus on demonstrating a reduction in side effects of topical over oral medications and raising awareness of chemopreventive options for breast cancer to increase acceptance of preventive medications.
Citation Format: Karavites LC, Allu S, Khan SA, Kaiser K. Awareness and acceptability of skin application of preventive medications for breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-13.
Abstract P6-13-07: The taccalonolides are novel microtubule stabilizers that covalently bind tubulin and have in vivo efficacy in drug resistant tumors
Authors: Risinger AL , Li J , Benavides R , Kuhn JG , Mooberry SL 
Published: May 2016

Abstract
Some of the most effective drugs used in the treatment of breast cancer are microtubule stabilizers. However, there are limitations to their clinical efficacy, including inherent and acquired drug resistance. All microtubule stabilizers that are currently approved for clinical use bind within the taxane pocket on β-tubulin in a reversible manner. The taccalonolides are a novel class of microtubule stabilizers that have a similar profile of microtubule stabilization as the taxanes, but circumvent drug resistance mediated by expression of drug efflux pumps, mutations in the taxane binding site, or overexpression of the βIII isotype of tubulin. We have shown that one important difference between the taccalonolides and clinically approved microtubule stabilizers is that the taccalonolides form a covalent bond to β-tubulin. This distinct interaction allows for irreversible binding, which explains their ability to avoid drug efflux mechanisms and likely belies their exquisite potency in in vivo antitumor models which allows for delivery in aqueous solvents. Serum stability and binding studies, microsomal clearance and pharmacokinetic analysis were performed with both taccalonolides AF and AJ to more fully understand the properties of this class of compounds. We found that both taccalonolides had low microsomal intrinsic clearance rates with no evidence of serum binding and had half-lives similar to paclitaxel in vivo. Like other microtubule targeted agents, taccalonolide AF has a narrow therapeutic window with antitumor effects accompanied by body weight loss. Interestingly, direct injection of taccalonolide AF into a xenograft tumor was highly effective with no associated toxicities at low doses, indicating that targeted delivery to the tumor would greatly increase the efficacy and decrease toxicities. To this end, efforts to promote the targeted delivery of taccalonolide AF to the tumor are being evaluated.
Citation Format: Risinger AL, Li J, Benavides R, Kuhn JG, Mooberry SL. The taccalonolides are novel microtubule stabilizers that covalently bind tubulin and have in vivo efficacy in drug resistant tumors. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-07.
Abstract P6-13-18: Triple-negative kinase profile guides in the selection of the multi-kinase inhibitor EC70124 as an active antitumor agent
Authors: Perez-Peña J , Serrano-Heras G , Corrales-Sánchez V , Nieto-Jimenez C , Gascón-Escribano MJ , Montero JC , Moris F , Martin M , Pandiella A , Ocana A 
Published: May 2016

Abstract
Introduction: Identification of the kinase profile of triple negative tumors can guide in the selection of active multi-kinase inhibitors. We describe the preclinical selection of a novel kinase inhibitor based on the kinase profile identified in human samples.
Methods: phosphokinase profiles of human samples were performed using two kinase arrays: human phospho-RTK array kit (# ARY001, R&D Systems, Abingdon, UK) and the PathScan RTK Signaling Antibody Array Kit (# 7982,Cell Signaling Technology). Based on the kinase profile, inhibitors against activated proteins were evaluated in a panel of triple negative cell lines. Proliferation and growth was measured by MTT uptake. Evaluations of apoptosis and cell cycle were performed by flow cytometry using Annexin V and propidium iodide, respectively. Gene-set enrichment analyses were performed to identify relevant functions mediated by the drug and the identified genes were confirmed by RT-PCR. The in vivo antitumoral effect was evaluated using xenografted animals.
Results: Several kinases were constitutive activated in human tumors, including AKT and pS6, among others . Pharmacological screening identified PI3K/mTOR inhibitors as the most active agents. The novel multi-kinase inhibitor, EC-70124 showed clear antitumor activity. Doses of EC70124 in the nanoMolar ranged reduced proliferation and cell growth in a panel of triple negative cell lines including HS578T, BT549, MDA-MB231 and HCC3153. Treatment with EC70124 inhibited the PI3K/mTOR pathway and induced DNA damage. Gene set enrichment analyses showed different cellular functions induced by the compound. EC70124 showed activity in xenografted animals. Pharmacodynamic analyses supported the inhibition of the PI3K/mTOR pathway in vivo.
Conclusion: the kinase profile of human triple negative tumors identified major activated pathways including the PI3K/mTOR route. The novel kinase inhibitor EC70124 inhibited the PI3K/mTOR pathway showing clear antitumor activity. Evaluation of the kinase profile followed by functional studies is an attractive approach to rationally select active antitumoral agents.
Citation Format: Perez-Peña J, Serrano-Heras G, Corrales-Sánchez V, Nieto-Jimenez C, Gascón-Escribano MJ, Montero JC, Moris F, Martin M, Pandiella A, Ocana A. Triple-negative kinase profile guides in the selection of the multi-kinase inhibitor EC70124 as an active antitumor agent. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-18.
Abstract P6-17-06: Relevance of the hyaluronidase-1 (HYAL1) in brain metastasis formation of breast cancer patients
Authors: Oliveira-Ferrer L , Anna M , Wickman H , Matschke J , Schumacher U , Milde-Langosch K , Müller V , Witzel I 
Published: May 2016

Abstract
The incidence of brain metastases in breast cancer (BMBC) patients has increased in the last years and represents the major life-limiting problem for metastatic breast cancer (BC) patients. However, the knowledge about tumor cell invasion in the brain is still very limited and new markers for brain metastasis incidence are urgently needed in order to early detect high risk patients.
In a recent study based on cDNA microarray data of primary breast tumors, we could show that mRNA expression of certain glycosylation enzymes significantly correlates with an organ-specific metastatic spread. Interestingly, hyaluronan synthase 2 (HAS2) and hyaluronidase-1 (HYAL1), both genes involved in hyaluronan (HA) metabolism, showed an independent prognostic value and a significant correlation with brain metastasis formation.
In order to corroborate the role of these enzymes at protein level, we examined the expression of HYAL1 and HAS2 on a tissue microarray including 200 primary BC samples. Here, the prognostic impact of HAS2 could not be validated, whereas for HYAL1 shorter disease free survival (DFS) was observed for patients with high HYAL1-expression levels. This trend could be additionally verified in a second cohort of 107 BC samples, using western blot analysis. Moreover, significantly higher HYAL1 expression was detected among primary tumors with subsequent brain metastases compared with those without brain metastases using immunohistochemistry (IHC).
No impact of HYAL1 expression on disease progression of BCBM patients could be observed after analysis of 87 brain metastasis samples. Here, quantification of tumor-associated HA revealed a significant positive correlation with triple negative tumors and a trend towards shorter progression-free survival.
Taken together, our data suggest a role of the enzyme HYAL1 for progression and especially for the development of brain metastases in breast cancer patients.
Citation Format: Oliveira-Ferrer L, Anna M, Wickman H, Matschke J, Schumacher U, Milde-Langosch K, Müller V, Witzel I. Relevance of the hyaluronidase-1 (HYAL1) in brain metastasis formation of breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-06.
Abstract PD2-08: Potential role of prolactin signaling in development and growth of the lobular subtype of breast cancer
Authors: Oesterreich S , Katz TA , Logan G , Levine K , Nagle A , Huo Z , Tseng GC , Rui H , Lee AV , Butler LM 
Published: May 2016

Abstract
Invasive lobular carcinoma (ILC) is the eighth most frequently diagnosed cancer in any organ, and accounts for 8-11% of breast cancer. This histological subtype is characterized by loss of E-cadherin, and favorable prognostic factors, such as low Ki67 and high rates of ER/PR-positive tumors. Only recently is the lobular subtype gaining recognition as a distinct disease, displaying a unique growth pattern, unique molecular changes in addition to loss of E-cadherin, and evidence for late recurrences and reduced response to targeted endocrine therapy. It is widely accepted that a late age at first full term birth (FFTB) increases a women's risk for breast cancer. Interestingly, several published epidemiological studies have shown that the increased risk after a late age at FFTB is preferential for the lobular subtype of breast cancer compared to the ductal subtype. We therefore hypothesized that pregnancy hormones like prolactin play an integral role in the development and progression of ILC. Interrogation of the Cancer Genome Atlas (TCGA) data revealed a high expression of milk protein genes as well as prolactin signaling molecules, specifically Stat5a and Stat5b in lobular carcinomas compared to ductal carcinomas. We developed a lactation score including 7 milk protein genes and found that in the TCGA data set ILC tumors have a significantly higher lactation score than IDC tumors. Additionally, we found that ILC cell lines express increased prolactin receptor mRNA and protein levels compared to IDC cell lines. Prolactin treatment in ILC and IDC cells reveals divergent signaling pathways - prolactin stimulates ERK activation in IDC but not ILC cells. We are currently further delineating the prolactin signaling pathways, and resulting phenotypes, comparing ILC and IDC cells. We expect these experiments to move the field forward by establishing a relationship between prolactin and lobular carcinoma.
Citation Format: Oesterreich S, Katz TA, Logan G, Levine K, Nagle A, Huo Z, Tseng GC, Rui H, Lee AV, Butler LM. Potential role of prolactin signaling in development and growth of the lobular subtype of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-08.