bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-07-09: CPM rate among individuals with breast cancer who underwent multiplex gene testing for hereditary cancer: Single institution experience
Authors: Elsayegh N , Gutierrez Barrera AM , Kuerer HM , Hernandez ND , Litton JK , Arun BK 
Published: March 2017

Abstract
Background: Availability of multiplex gene (MPG) testing for hereditary cancer has led to increase use of panel testing versus single gene testing for hereditary cancer. These panels include high, but also moderate penetrance genes. For some of these genes, associated cancer risk and risk management guidelines do not exist. Furthermore there is a high rate of variant of unknown significant (VUS) findings in non-BRCA genes. Currently, in the absence or minimal available data, health care providers and patients are faced with important risk management decisions, especially regarding preventive surgeries, such as prophylactic mastectomy. Currently, there is no data regarding prophylactic mastectomy rate among patients with breast cancer who underwent (MPG) testing. Therefore, our aim was to evaluate the rate of contralateral prophylactic mastectomy (CPM) in a cohort of individuals who underwent multiplex gene testing. Methods: Eight hundred thirty five patients with breast cancer who underwent MPG testing between the years 2013 and 2016 were identified using Institutional Clinical Cancer Genetics Database. Patients with pathogenic, likely pathogenic variants or who had a VUS were included in the analysis. Results: Of 835 patients with a diagnosis of breast cancer; 105 (13%) had a pathogenic or likely pathogenic mutation: 29 (28%) BRCA1, 26 (25%) BRCA2, 11 (11%) ATM, 2 (2%) BARD1, 3 (3%) BRIP, 9 (9%) CHEK2, 1 (1%) MSH2, 1 (1%) NBN, 5 (5%) PALB2, 4 (4%) PTEN, 1 (1%) RAD51C, 5 (5%) TP53, 4 (4%) CDH1, 2 (2%) MUTYH, 1 (1%) PMS2, 1 (1%) APC (1). A total of 102 (12%) VUS were found. Average age of diagnosis was 44 (Range 21-81). CPM rate was 32% (n=66) for the total cohort. Twenty nine % (n=19) of patients with non-BRCA mutations, 24.2% (n=16) with VUS and 46% (n=31) with BRCA mutations opted for CPM. Conclusion: Overall 32% of breast cancer patients with germline mutations or VUS opt for CPM at our institution. The rate for CPM in non- BRCA mutations carriers is high despite no available data regarding contralateral breast cancer risk and benefit of CPM. This finding should be validated in larger cohorts, including identification of reasons behind decision for CPM in these cohorts.
Citation Format: Elsayegh N, Gutierrez Barrera AM, Kuerer HM, Hernandez ND, Litton JK, Arun BK. CPM rate among individuals with breast cancer who underwent multiplex gene testing for hereditary cancer: Single institution experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-09.
Abstract P2-08-01: Results from a randomized placebo-controlled phase 2 trial evaluating exemestane ± enzalutamide in patients with hormone receptor–positive breast cancer
Authors: Krop I , Abramson V , Colleoni M , Holmes FA , Estevez L , Hart L , Awada A , Zamagni C , Morris P , Schwartzberg L , Chan S , Wheatley D , Guculp A , Biganzoli L , Steinberg J , Gianni L , Trudeau M , Kelly CM , Uppal H , Tudor IC , Peterson A , Winer E , Yardley DA 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P2-15-02: Attitudes towards tissue donation for rapid autopsy among community and academic oncologists
Authors: Rajagopal PS , Lee A , Puhalla SL 
Published: March 2017

Abstract
Rapid autopsy (RA) refers to the recently developed practice of obtaining research tissue within 2-6 hours following the death of a patient. Such tissue can offer insights into the genomic and proteomic evolution of metastatic disease and possible novel therapeutic targets. Although patients generally have positive attitudes towards RA, RA programs have not been widely established by oncologists at healthcare centers with these capabilities. To identify barriers to our adoption of an RA program, we conducted a 21-item web-based survey of academic and community oncologists in a single institution with regard to knowledge, attitudes and concerns about RA. Twenty-six physicians completed the study out of a possible 98 respondents, with 50% in academic practice and 50% in community practice. 46% were not aware of RA prior to the survey. None of the community physicians had experience with patient tissue donations of any kind. In completing the survey, 85% were willing to ask future patients about participating in RA. 58% of oncologists cited lack of awareness as their primary barrier to participation, while 31% reported discomfort in discussing rapid autopsy with patients or concern about the doctor-patient relationship. A minority of physicians had ethical concerns about the practice. The most popular strategies for increasing awareness of the RA program included distributing informational pamphlets to patients, using a third-party advocate or a discussion with the patient's primary oncologist or NP. 92% of those surveyed stated that being aware of patient interest would make them much more likely to recommend RA to patients. Our study is among the first to clarify barriers among oncologists, particularly community oncologists, to establishing RA programs and suggests that increased information alone with clarification of patient perceptions could provide substantial progress in developing RA programs at tertiary healthcare centers and recruiting patients to these programs.
Citation Format: Rajagopal PS, Lee A, Puhalla SL. Attitudes towards tissue donation for rapid autopsy among community and academic oncologists [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-15-02.
Abstract P3-01-06: Visualizing the real difference between 2-D and 3-D specimen mammography
Authors: Kaufman CS , Zacharias K 
Published: March 2017

Abstract
BACKGROUND: Specimen mammography aids in the determination 1) if the target lesion has been removed and 2) whether there is a clear margin at excision. In the past, two orthogonal views using 2-D imaging has been considered to be equivalent to a three dimensional perspective. Yet tomosynthesis for screening mammography has demonstrated the value of thin sliced imaging over two view screening mammography. In March, 2015, we began using true 3-D tomosynthesis of breast specimens at lumpectomy and have compared 2-D and 3-D specimen mammography.
METHODS: We have examined 125 consecutive breast cancer patients with both 2-D and 3-D imaging of the same specimens since March 2015. The circulating nurse would take the specimen and obtain two orthogonal views using both 2-D and 3-D devices with images sent to the radiology department. It was not felt ethical to blind the surgeon from having both images available to make an intraoperative clinical decision regarding immediate re-excision. We compared the data noted from each method and which method best aided the decision to perform immediate re-excision, and time required to obtain the images.
RESULTS: We have studied 125 patients over 11 months since March 2015. Confirmation of complete lesion excision was easier with 3-D tomosynthesis than with 2-D as the 3-D slice did not include overlying skin or dense breast tissue surrounding the lesion in the image, making the target lesion stand out more clearly. Although the 2-D images appear to have higher contrast than the individual 3-D slices, the tomosynthesis 3-D images contained more actionable data than the 2-D. Also decisions to excise more tissue during the procedure were enabled by the additional information included in the 3-D images. In addition, the 3-D images provided the depth of field to enable accurate re-excision using the Z-axis (see figures). Finally, it took about a minute longer to obtain and review the 3D images, although this difference did not delay surgical decisions nor prolong operative time.
CONCLUSIONS: 3-D specimen tomosynthesis facilitates the reduction of post-operative re-excision for lumpectomy patients by providing more information than 2-D orthogonal views, providing easier, more accurate confirmation of the extent of the target excision. Additionally, serial 1mm slices of the specimen allowed the integration of Z-axis targeting, ensuring that any necessary margin excision during surgery was accomplished immediately with maximum tissue conservation. More studies are planned to further validate these findings of these first 125 patients.
Citation Format: Kaufman CS, Zacharias K. Visualizing the real difference between 2-D and 3-D specimen mammography [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-01-06.
Abstract P3-03-18: An ex-vivo platform predicts anti-tumor outcome of metabolically-targeted, algorithm-driven combination therapy in triple-negative breast cancer
Authors: Goldman A , Majumder B , Dhawan A , Kohandel M , Majumder P , Sengupta S 
Published: March 2017

Abstract
Cancer cells undergo phenotypic cell state transitions in response to chemotherapy as a mechanism that can confer transient resistance. However, such cell state transitions can also unlock unique vulnerabilities that can be exploited using temporally-sequenced combination chemotherapy. Here, utilizing a primary breast cancer ex-vivo functional assay that captures tumor heterogeneity, we report that in response to a chemotherapeutic agent, a subset of cancer cells can mount an acutely-induced phenotypic adaptive resistance to future cytotoxic pressure via the transient acquisition of a unique metabolic state defined by augmented glycolysis together with mitochondrial proficiency. These cells activate two complex, temporally-interdependent pathways that enable a glucose shunt towards the pentose phosphate pathway (PPP), which confers an adaptive cross-tolerance to different chemotherapeutic agents. Mathematically modeling these pathways, and simulating drug schedules, we define a rationally-designed 3-drug combination therapy of metabolic inhibitors and cytotoxic agents, which results in improved cancer survival. Our findings highlight a new bioenergetics-based adaptive resistance mechanism through which cancer cells can survive combinations of chemotherapy. Administration of metabolic inhibitors in rational, temporal sequence with existing chemotherapy can emerge as a new paradigm in the treatment of cancer.
Citation Format: Goldman A, Majumder B, Dhawan A, Kohandel M, Majumder P, Sengupta S. An ex-vivo platform predicts anti-tumor outcome of metabolically-targeted, algorithm-driven combination therapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-03-18.
Abstract P3-04-25: Role of H19, a long non-coding RNA, in development of resistance to endocrine therapy in breast cancer cells
Authors: Basak P , Chatterjee S , Bhat V , Jin H , Su A , Murphy LC , Raouf A 
Published: March 2017

Abstract
Introduction:
Majority of breast cancer tumors are Estrogen receptor positive (ER+) where antiestrogen therapies (endocrine therapies) are the best therapeutic strategy to treat this type of tumors. However, eventually over 30% of patients will develop resistance to endocrine therapies resulting in disease relapse. We recently showed that the long noncoding RNA, H19, is an estrogen target gene that plays a significant role in estrogen-induced proliferation of the normal and malignant ER+ cells. We therefore hypothesize that H19 expression is also important to the proliferation of endocrine therapy resistant cells. In this study, we examined if estrogen-independent H19 expression is important to the development of endocrine therapy resistance.
Objective:
The overall objective of this project is to use therapy sensitive (MCF-7) and therapy-resistant (LCC9) breast cancer cells as model systems to examine the role of long non-coding RNA H19 in development and maintenance of resistance to endocrine therapy.
Methodology and Results:
We examined the expression of H19 in ER+ breast cancer cells (MCF7) that under the selective pressure of fulvesterant (ICI, ER down regulator) acquire resistance to ICI. We observed that while H19 expression was initially decreased as expected, its expression subsequently increased in the ICI-resistant MCF7 cells. Interestingly, H19 knockdown in MCF7 cells significantly decrease their proliferation as determined by Flowcytometry and made them more sensitive to ICI. We also examined H19 expression in the ICI-resistant LCC9 cells and found that ICI treatment increased H19 expression. Interestingly, H19 knockdown in the LCC9 cells decreased their proliferation and surprisingly made them sensitive to ICI treatment. Previous observations indicate that NOTCH4 receptor (NR4) may be involved in endocrine therapy resistance. Interestingly we found that in presence of ICI, NR4 expression is increased and that forced activation of NR4 markedly increases H19 expression in LCC9 cells.
Conclusion:
Altogether these observations suggest that H19 plays an important role in the development of endocrine therapy resistance and further our understanding of the cellular and molecular mechanisms involved in endocrine therapy resistance. These and similar studies could potentially lead to the development of new therapies to treat therapy resistant tumor cells. Further experiments would reveal if signalling pathways that regulate H19 expression independent of estrogen are useful therapies against endocrine therapy resistant tumors.
Citation Format: Basak P, Chatterjee S, Bhat V, Jin H, Su A, Murphy LC, Raouf A. Role of H19, a long non-coding RNA, in development of resistance to endocrine therapy in breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-25.
Abstract P3-07-07: Inhibition of death-associated protein kinase 1 enhances chemotherapy action against triple-negative breast cancer
Authors: Zhao D , Zhao J , Mazumadar A , Bollu L , Shepherd J , Ma Y , Zhang Y , Hill JL , Savage MI , Brown PH 
Published: March 2017

Abstract
Background: Triple negative breast cancers (TNBCs) are the most aggressive ER negative breast cancers with limited therapy strategies and poor prognosis. P53 gene is frequently mutated in approximately 80% of TNBCs. To identify novel molecular targets for ER negative breast cancer, particularly the more aggressive TNBC, we conducted a human kinome screen and identified death-associated protein kinase 1 (DAPK1) as one of the kinases that are highly expressed in ER negative breast cancer. Deletion or inhibition of DAPK1 suppresses growth of p53-mutant but not p53-wildtype breast cancer cells. Here we investigate whether DAPK1 inhibition will enhance chemotherapy action against p53-mutant TNBCs.
Experimental design and methods: We performed experiments to test cell growth of p53-mutant TNBCs that were treated with DAPK1 siRNA or DAPK1 inhibitors in combination with different doses of chemotherapy drugs including 5-FU (5-Fluorouracil), doxorubicin, cisplatin, PARP inhibitor (BMN673), paclitaxel, gemcitabine and vinorelbine.
Results: Our results show that DAPK1 inhibitors enhance the growth inhibitory effects of cisplatin and PARP inhibitor in p53-mutant TNBCs. Furthermore, combined DAPK1 inhibition (via siRNA knockdown) with cisplatin synergistically inhibits cell growth of p53-mutant TNBCs.
Conclusion: DAPK1 is a novel, promising target for the treatment of triple-negative p53-mutant breast cancer. Our studies demonstrate that DAPK1 inhibition sensitizes TNBCs to the cytotoxic effects of cisplatin or the PARP inhibitor. We are now conducting studies to determine whether DAPK1 inhibition will sensitize TNBC tumors and patient-derived TNBC xenografts to the effects of cisplatin and PARP inhibition. These studies suggest that the combination of DAPK1 inhibition with drugs that interfere with DNA repair will be useful for the treatment of the most aggressive form of breast cancer, triple-negative breast cancer.
Funding: This study was funded by a Susan G. Komen Promise grant (SAB12-00006 to P.H. Brown), a MD Anderson Knowledge Gap Moonshot grant (to P.H. Brown) and a Breast Cancer Research Foundation grant (BCRF 15101807, 2015–2016 to P.H. Brown).
Citation Format: Zhao D, Zhao J, Mazumadar A, Bollu L, Shepherd J, Ma Y, Zhang Y, Hill JL, Savage MI, Brown PH. Inhibition of death-associated protein kinase 1 enhances chemotherapy action against triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-07-07.
Abstract P3-12-05: Estimating costs of relapsing HER2+ breast cancer in Spain
Authors: Colomer R , Ciruelos E , De la Haba J , Martín M , De Salas-Cansado M , Muñoz-Molina B , Albanell J 
Published: March 2017

Abstract
OBJECTIVES: The purpose of this study was to describe the economic impact of recurrences (locoregional or unresectable/metastatic recurrences [MR]) in patients with HER2+ breast cancer (BC) in Spain.
METHODS: A Delphi panel of 15 Spanish oncologists was carried out to define the clinical management (patients' flow and healthcare resources use) of locoregional recurrences (LR) and unresectable or MR in patients with HER2+ BC. Healthcare resources included medication, medical visits, lab and imaging tests, hospitalizations, surgery, adverse events management and treatment of specific metastases (e.g. bone metastases). Additionally, loss of productivity was also estimated. Local unit costs where used in combination with healthcare resources and workdays lost to estimate both the direct and indirect costs of LR and MR in HER2+ BC patients. A deterministic sensitivity analysis was performed to explore the robustness and assess the critical variables of the study.
RESULTS: The estimated distribution of recurrences in HER2+ BC patients was: 90% of MR, 7% of LR and 3% of LR followed by an MR. With respect to MRs, 31% of cases were estimated to receive up to 5 lines of treatment whilst 5% received no treatment (10%, 20% and 21% would receive 2, 3 and 4 treatment lines, respectively, with a median of 3 lines). Treatment regimens including trastuzumab were the most frequently used (in combination with pertuzumab and taxane in 1L, and with other combinations in 4&5L). In 3L, the most common treatment regimen was lapatinib-capecitabine. Total costs, including medical and indirect costs were €235,138, being the direct costs more than 88.7% (€208,682). Both direct and total costs were higher in patients being treated with a higher number of treatment lines, with figures ranging from €38,511 (1L) to €308,869 (5L) and €50,908 (1L) and €358,000 (5L) respectively.
CONCLUSIONS: HER2+ BC patients with a MR were estimated to receive a median of 3 treatment lines and almost one third receives 5 treatment lines. The direct and indirect costs of recurrences are high, with a calculated average total cost of €235,138. Using targeted therapies in earlier stages of HER2+ BC that achieve a reduction of recurrences would achieve significant cost savings in Spain.
Citation Format: Colomer R, Ciruelos E, De la Haba J, Martín M, De Salas-Cansado M, Muñoz-Molina B, Albanell J. Estimating costs of relapsing HER2+ breast cancer in Spain [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-12-05.
Abstract P4-01-11: Diagnostic performance of supplemental screening with molecular breast imaging in women with dense breast tissue
Authors: Redfern RE , Shermis RB , Chen JT , Kudrolli H 
Published: March 2017

Abstract
Purpose: The aim of this study was to retrospectively assess the diagnostic performance of molecular breast imaging (MBI) as a supplementary screening tool for women with dense breast tissue. We had previously reported excellent cancer detection rates and positive predictive values, whereas in this report we present 1-year follow up data and present sensitivity, specificity and negative predictive values. Methods: Molecular Breast Imaging (MBI) was implemented in routine clinical practice at a large, community-based breast imaging center. Women 25 to 90 years of age with dense breasts and negative mammogram results who underwent subsequent screening with 300 MBq (8 mCi) 99mTc-sestamibi MBI were retrospectively analyzed. Outcome measures included sensitivity, specificity, and positive and negative predictive values. Results: In 1,376 women with a complete reference standard, 17 (1.2%) were diagnosed with cancer. MBI detected cancer in 15 subjects such that 2 interval cancers occurred and were considered false negatives. Of those 17 cancers, 1 (5.9%) were ductal carcinoma in situ only, 13 were invasive tumors (76.5%); 1 (5.9%) patient was diagnosed with bilateral disease. Overall sensitivity of MBI in this sample was 88.2% (95% CI 63.6 – 98.5), while specificity was also high at 92.4% (95% CI 90.9 – 93.8). Positive predictive value for recall (PPV1) was 12.7% (95% CI 7.3 – 20.1), while negative predictive value for recall (NPV1) was calculated as 99.8% (95% CI 99.4 – 100.0). Conclusions: When incorporated into a community-based clinical practice environment, MBI demonstrated high sensitivity, specificity and negative predictive value. These results demonstrate the utility of MBI as a supplementary screening tool to mammography for women with dense breasts.
Citation Format: Redfern RE, Shermis RB, Chen JT, Kudrolli H. Diagnostic performance of supplemental screening with molecular breast imaging in women with dense breast tissue [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-11.