bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract CS1-2: Contralateral prophylactic mastectomy: Patient preferences and risk perceptions
Authors: Partridge Ann 
Published: May 2015

Abstract
Recent studies have revealed increasing rates of contralateral prophylactic mastectomy (CPM) among women with unilateral early stage breast cancer. Bilateral mastectomy at diagnosis of unilateral breast cancer is particularly common among young women, with younger age consistently identified as a predictor of CPM. This trend for more surgery rather than less has raised concerns, given the lack of evidence for a survival benefit from CPM and the relatively low risk of contralateral breast cancer for most women in this setting. Although mastectomy is a safe procedure and major complications are rare, there are potential negative consequences including cosmetic concerns and clinically significant potential long-term sequelae such as numbness of the chest skin and chronic pain and decreased function. Given most women opt for reconstructive surgery, extended recovery time, additional surgical complications, and decreased strength or function due to muscles being moved or stretched are also additional risks. Recent data have revealed that some women who undergo CPM have misperceptions about their actual risks and the values of the prophylactic surgery. In a recent cross-sectional survey of young breast cancer survivors who had undergone bilateral mastectomy for unilateral breast cancer, most women indicated that desire to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk. An increasing body of literature suggests that fear of recurrence and anxiety are strong predictors of undergoing CPM. Improved education and counseling about the risks and benefits of CPM, as well as increased awareness and management of anxiety surrounding breast cancer diagnosis and treatment, are likely to help patients to understand their risks more fully and to make decisions consistent with their preferences and values. Decision aids may be particularly useful in this setting.
Citation Format: Ann Partridge. Contralateral prophylactic mastectomy: Patient preferences and risk perceptions [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr CS1-2.
Abstract ES8-2: Circulating plasma tumor DNA as biomarkers for breast cancer therapy
Authors: Park Ben Ho 
Published: May 2015

Abstract
Currently, oncologists use prior clinical trials data to recommend therapies based upon features of the tumor and clinical stage of the patient. A limitation with this approach is that these data are averaged from large groups of patients that are then applied to each individual. This creates uncertainty as there is currently no reliable method to identify whether an individual patient truly is at risk for an unfavorable outcome and would benefit from a specific intervention. Recently, we and others have demonstrated the feasibility of detecting circulating plasma tumor DNA in metastatic breast cancer patients using digital PCR. We have now extended these studies to include early stage breast cancer patients using the second generation platform of droplet digital PCR (ddPCR). In this study the feasibility and accuracy of circulating plasma tumor DNA (ptDNA) detection was prospectively assessed by screening for the presence of tumor PIK3CA mutations in patients' plasma prior to and after breast surgery using ddPCR. We observed in early stage breast cancer patients that ddPCR could detect PIK3CA mutations preoperatively with 93.3% sensitivity (14 of 15 mutations detected) and 100% specificity (no false positives in 30 tumors). Moreover, 5 of 10 patients with PIK3CA mutation positive tumors continued to have mutant PIK3CA detected in their postoperative blood sample despite having no clinical evidence of disease. This work demonstrates that droplet digital PCR (ddPCR) can be used to accurately detect cancer DNA mutations in the blood of early stage breast cancer patients including those with minimal, clinically undetectable disease. Our results suggest that ddPCR provides an accurate and relatively non-invasive method for measuring residual disease and could be developed as a biomarker to identify early stage breast cancer patients at higher risk for recurrence to help make informed decisions regarding adjuvant therapies. Ongoing studies assessing mutational profiles from ptDNA from metastatic patients as well as patients undergoing neoadjuvant therapies will be discussed.
Citation Format: Ben Ho Park. Circulating plasma tumor DNA as biomarkers for breast cancer therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES8-2.
Abstract OT1-1-13: A Phase 2, randomized, open-label, multicenter, safety and efficacy study of oral lucitanib in patients with metastatic breast cancer with alterations in the FGF pathway
Authors: Abu-Khalaf Maysa , Mayer Ingrid , Litten Jason B , Raponi Mitch , Allen Andrew R , Pusztai Lajos , Arteaga Carlos L 
Published: May 2015

Abstract
BACKGROUND: Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of Fibroblast Growth Factor Receptors 1-3 (FGFR1-3), Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3) and Platelet-Derived Growth Factor Receptors A/B (PDGFRA/B). Aberrant FGF signaling, as defined as FGFR1 and/or 11q amplification, is a hallmark genomic alteration in breast cancer, observed at a combined frequency of up to 25% of patients. Breast cancer patients with measurable disease and aberrant FGF signaling treated in the ongoing Phase 1/2 clinical trial of lucitanib monotherapy experienced an ORR of 50% and a DCR of 100%. This compelling clinical activity has led to the initiation of a global clinical development program for lucitanib in breast cancer.
TRIAL DESIGN: The current study is comparing PFS for doses of lucitanib (10 or 15 mg daily) in patients with FGF-aberrant metastatic breast cancer after failure of currently available standard therapies. Approximately 160 patients will be randomized 1:1 to the 10 mg and 15 mg daily dosing groups and stratified by FGF pathway alteration (FGFR1 or 11q amplification) and prior anti-VEGF therapy (yes or no). FGFR1 and 11q (containing the FGF ligands 3, 4, and 19) amplification is determined locally for patient enrolment and confirmed by central laboratory fluorescent in situ hybridization (FISH) testing. A total of 130 PFS events provides 80% power at a 2-sided significance level of 0.05 to detect a hazard ratio of 0.60 for comparing the 10 mg and 15 mg dose groups. Secondary objectives are ORR, DoR, DCR, OS, PROs, safety and population PK. Exploratory endpoints include tissue and blood-based biomarkers that may be predictive of response or primary resistance to treatment with lucitanib.
ELIGIBILITY CRITERIA: Histologically or cytologically confirmed FGF-aberrant metastatic breast cancer relapsed or refractory to approved standard available treatment. ECOG 0 or 1. Normal organ function. Patients with uncontrolled hypertension are excluded.
Citation Format: Maysa Abu-Khalaf, Ingrid Mayer, Jason B Litten, Mitch Raponi, Andrew R Allen, Lajos Pusztai, Carlos L Arteaga. A Phase 2, randomized, open-label, multicenter, safety and efficacy study of oral lucitanib in patients with metastatic breast cancer with alterations in the FGF pathway [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-13.
Abstract OT3-1-07: MotHER: A US registry for women with breast cancer who have received trastuzumab, pertuzumab in combination with trastuzumab, or trastuzumab emtansine (T-DM1) during pregnancy or within 7 months prior to conception
Authors: Brown Vikki , Miller Richard K , Chu Laura , Chow Cheryl , Trudeau Caroline , Andrews Elizabeth B 
Published: May 2015

Abstract
Background: Trastuzumab (Herceptin) and pertuzumab (Perjeta) are HER2-targeted monoclonal antibodies, and T-DM1 (Kadcyla) is a HER2-targeted antibody–drug conjugate. These molecules are classified as FDA Pregnancy Category D, indicating evidence of fetal harm; there have been postmarketing reports of oligohydramnios in women who received trastuzumab during pregnancy; in non-clinical studies of pertuzumab, oligohydramnios, delayed renal development, and embryo-fetal death occurred in pregnant cynomolgus monkeys. Furthermore, maytansine, the parent molecule of DM1, has demonstrated embryotoxicity in mice. The MotHER pregnancy registry was established in 2008 as an FDA postmarketing commitment to evaluate the effects of trastuzumab on pregnancy outcome. Pertuzumab and T-DM1 were included in the registry following their respective FDA approvals in 2012 and 2013.
Study design: MotHER is a US pregnancy registry and uses a prospective, observational cohort design. Enrollment is voluntary and can be initiated by the patient or her healthcare provider. Women are followed up until pregnancy outcome; infants are followed up through the first year of life.
Eligibility criteria: Pregnant women ≥18 years of age and resident in the US are eligible if they have received at least one dose of trastuzumab, pertuzumab in combination with trastuzumab, or T-DM1 for breast cancer during pregnancy or within 7 months prior to conception. Enrollment must be initiated before pregnancy outcome is known.
Specific aims: The primary outcome measures are pregnancy outcomes and the incidence of pregnancy complications, such as oligohydramnios, congenital anomalies, and fetal/infant functional deficits. Information on potential birth defects, noted either at birth or during pediatric follow-up, is evaluated and classified by a birth defect evaluator/clinical geneticist.
Statistical methods: The study is descriptive and not designed for formal hypothesis testing; event rates with 95% confidence intervals will be calculated.
Accrual: There is no pre-specified sample size. Data collection is ongoing, from 2009 to 2019 for trastuzumab, from 2012 to 2022 for pertuzumab plus trastuzumab, and from 2013 to 2023 for T-DM1. Fourteen women have enrolled as of January 31, 2014.
Citation Format: Vikki Brown, Richard K Miller, Laura Chu, Cheryl Chow, Caroline Trudeau, Elizabeth B Andrews. MotHER: A US registry for women with breast cancer who have received trastuzumab, pertuzumab in combination with trastuzumab, or trastuzumab emtansine (T-DM1) during pregnancy or within 7 months prior to conception [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-07.
Abstract P1-07-06: Activation of oncogenic pathways by mitochondrial reprogramming in triple negative breast cancer
Authors: Park Jun Hyoung , Kumar Santhosh , Vithayathil Sajna , Arora Kavisha , Putluri Nagireddy , Tsouko Efrosini , Donti Taraka R , Frigo Daniel E , Creighton Chad J , Lewis Michael T , Sreekumar Arun , Wong Lee-Jun , Kaipparettu Benny Abraham 
Published: May 2015

Abstract
Triple negative breast cancer (TN BCa) Driver pathway is still poorly understood. Thus, it is important to identify the underlying mechanisms of triple negative breast cancer progression. Mitochondria, a semiautonomous organelle in cells, play an important role in cellular energy metabolism, free radical generation, and apoptosis. Mitochondria-nuclear crosstalk is a bidirectional pathway of communication between mitochondria and nucleus that influences many cellular and organismal activities. This crosstalk can regulate several oncogenic pathways involved in tumorigenesis. Using transmitochondrial cybrid (cybrid) technology, we generated different cybrid models under common nuclear background of TN BCa. Mitochondria from cells of different cancer potential including benign breast epithelium, moderately and highly metastatic breast cancer cell lines were used to understand cancer mitochondria regulated tumor pathways. Tumor and gene expression analysis suggested that among different cancer pathways, c-Src signaling pathway is one of the most consistently activated pathways in cybrids with TN BCa cancer mitochondria. Further analysis in parental cells and other tumor models suggested that autophosphorylation of c-Src is regulated by mitochondrial tumor characteristics. Our preliminary analysis also suggest that mitochondria targeted drugs are promising combination therapy for the management of Src-driven TN BCa. This finding is particularly important while considering the poor response rate observed after single drug therapy with Src family tyrosine kinase inhibitor Dasatinib in unselected TN BCa patients.
Citation Format: Jun Hyoung Park, Santhosh Kumar, Sajna Vithayathil, Kavisha Arora, Nagireddy Putluri, Efrosini Tsouko, Taraka R Donti, Daniel E Frigo, Chad J Creighton, Michael T Lewis, Arun Sreekumar, Lee-Jun Wong, Benny Abraham Kaipparettu. Activation of oncogenic pathways by mitochondrial reprogramming in triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-06.
Abstract P1-07-18: Loss of Rab1B promotes triple-negative breast cancer metastasis by activating TGF-β/Smad signaling
Authors: Jiang HongLin , Sun Hefen , Jin Wei 
Published: May 2015

Abstract
Background: Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype associated with poor prognosis. The onset of metastasis in organs such as the lung,bone and brain is a major cause of mortality in TNBC patients. Thus, identification of novel targets for the treatment of triple-negative breastcancer is urgent for improved outcomes in patients with this disease.
Methods and Results:Here we conducted quantitative proteomic analyses in breast cancer cell lines, which include a normal, primary tumor and a metastatic tumor that were isolated from a single patient. Stable isotope labeling of amino acid in cell culture followed by LC-MS/MS analysis was performed and deregulated proteins were identified using statistical analysis. We identified for the first time that Rab1B, a member of RAS oncogene family, was down-regulated in high metastatic human breast cancer cells. In a panel of breast tumor tissues, Immunohistochemical analysis demonstrated an inverse correlation between metastatic propensity and the expression of Rab1B. Compared with primary tumors, Rab1B expression was notably decreased in lymph node metastases. Low Rab1B expression also correlated with poorer survival in triple-negative breast cancer patients. Through in vitro assays, we confirmed that silencing of Rab1B expression by RNAi in MDA-MB-231 and MDA-MB-468 breast cancer cells, can potentiate the proclivity to metastasize in Transwell assay and enhance lung colonization by tail vain injection in mice. In a reverse-complimentary approach, we determined that elevated Rab1B expression in highly metastatic breast cancer cell lines (MDA-MB-231HM and MDA-MB-231Bo) can suppress the ability of invasion and metastasis in vitro and in vivo. Mechanistically, we establish that the metastatic behavior strongly correlates with increased phosphorylated Smad3 levels and overexpression of TGF-β type I receptor (TβRI). Conversely, restoration of Rab1B can inhibit the activation of this pathway in MDA-MB-231HM and MDA-MB-231Bo cells.
Conclusion:By utilizing a series of mammary tumor cell lines, animal models, and clinically sourced tissues, we demonstrate that Rab1B acts as a metastasis suppressor in triple-negative breast cancer through regulating TGF-β/Smad signaling pathway.
Citation Format: HongLin Jiang, Hefen Sun, Wei Jin. Loss of Rab1B promotes triple-negative breast cancer metastasis by activating TGF-β/Smad signaling [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-18.
Abstract P1-07-25: SSA, a novel sulindac sulfide derivative, inhibits tumor cell growth and invasion in breast cancer
Authors: Yi Bin , Feng Xiangling , Chang Hong , Ma Ruixia , Zhang Xiaoguo , Piazza Gary A , Xi Yaguang 
Published: May 2015

Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac sulfide (SS), have been reported for striking chemopreventive activities in various types of human malignances, including breast cancer. However, the toxicities related to cyclooxygenase (COX) inhibition resulting in suppression of physiologically important prostaglandins limit their clinical use for chemoprevention in human cancer. We recently developed a novel amine derivative of SS named as SSA, which lacks inhibitory effect on COX-1 or -2, yet shows 10 times greater suppressive effect than SS on growth of a panel of breast cells. Moreover, SSA treatment at sub-cytotoxic concentration (4μM) for 36 hr can significantly inhibit both migration and invasion of highly aggressive breast tumor MDA-MB-231cells. To understand the molecular mechanism accounting for this activity, we examined 4 oncogenic miRNAs, including mir-17-92, mir-9, mir-10b, and mir-21 that were previously reported by our group to be associated with SS anti-invasive activity in breast and colorectal cancer. We found SSA could significantly down-regulate these miRNAs; whereas their forced expression was able to counteract the anti-invasive activity of SSA in MDA-MB-231 cells. There results imply that significance of SSA with non-COX inhibitory properties in suppression of tumor cell invasion could provide novel insights into development of safer and more effective strategies for prevention of breast cancer progression and metastasis. In addition, after inducing mobility of non-invasive breast MCF-7 cells by using TGF-β1, we treated these invading cells with SSA and found that their mobility was significantly decreased. These results support anti-invasive activity of SSA in human breast cancer cells and inhibition of TGF-β1 as well as oncogenic miRNAs may be responsible for the mechanistic basis by which SSA prevents breast tumor cell invasion.
This study is supported by an American Cancer Society Research Scholar Grant (RSG-13-265-01-RMC) and NIH/NCI R21 Grants (5R21CA160280 and 1R21CA182754) to Yaguang Xi.
Citation Format: Bin Yi, Xiangling Feng, Hong Chang, Ruixia Ma, Xiaoguo Zhang, Gary A Piazza, Yaguang Xi. SSA, a novel sulindac sulfide derivative, inhibits tumor cell growth and invasion in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-25.
Abstract P1-07-26: Global analysis of the transcriptome in matched primary and metastatic tumours defines ER specific gene alterations
Authors: Vareslija Damir , Fagan Ailis , McBryan Jean , Buckley Patrick , Farrell Michael , Hill Arnold DK , Young Leonie 
Published: May 2015

Abstract
The incidence of brain metastasis (BM) among women with metastatic breast cancer (MBC) is currently on the rise, and it is estimated that between 10-30% of patients diagnosed with breast cancer may also develop BM (Weil 2005). BM is considered a late complication in the clinical setting and is an infrequent occurrence even in mice studies that readily metastasise to other organs (Valiente 2014). While pre-menopausal status and negative estrogen receptor (ER) status are seen as main risk factors (Gil-Gil 2013), it is now recognised that BM is emerging as an increasing clinical problem across the various MBC subtypes.
BM patients have very poor overall survival and as a result it is crucial to identify the factors that promote the survival and adaptation of breast cancer cells to allow them to colonise distant sites such as the brain. The ability to predict the BM potential could be of great clinical importance and in this study we decided to investigate the mechanisms underlying BM across the various MBC subtypes.
To our surprise, in a cohort of breast cancer patients we found a comparable number of ER positive and ER negative BM. We established that ER positive patients (n=10) had a substantially longer disease latency period (median disease free survival (DFS) 36 months, range 8-85 months) in comparison to ER negative patients (n=8, HER2 positive, n=2, triple negative, n=6), (median DFS 24 months, range 9-60 months). To understand and elucidate the gene alterations required for successful colonisation of the brain we undertook RNAseq of sequential primary and brain metastatic tumours from ER positive (n=4) and ER negative (n=3) breast cancer patients. Significant elevations in gene expression were observed in the brain metastatic tumours in comparison to the matched primary. Though a large degree of patient heterogeneity was observed, common ER-specific metastatic pathways were identified.
This study highlights the requirement of unique gene sets for the colonisation to the brain and that functional characterisation of the differentially expressed genes will enable the identification of novel molecular targets for prevention and treatment of breast cancer BM.
Citation Format: Damir Vareslija, Ailis Fagan, Jean McBryan, Patrick Buckley, Michael Farrell, Arnold DK Hill, Leonie Young. Global analysis of the transcriptome in matched primary and metastatic tumours defines ER specific gene alterations [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-26.