bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES9-1: Androgen Receptor in breast cancer. When might it serve as a suitable target?
Authors: Richer JK 
Published: February 2018

Abstract
In the last decade it has become clear that androgen receptors (AR) are present in the normal breast and are even more widely expressed in breast cancer than estrogen or progesterone receptors (ER or PR). The majority of estrogen receptor positive (ER+) breast cancers and a subset of triple negative breast cancer (TNBC) express AR. AR has long served as an effective therapeutic target In prostate cancer and potent drugs have been developed that either bind to AR or inhibit enzymes involved in androgen synthesis. In women, the primary source of androgens is the adrenal gland. Fat cells convert androgens to estrogens via the enzyme aromatase, the target of aromatase inhibitors. The relative abundance of the various steroid hormone receptors and context can affect the behavior of the receptors. Indeed, the role of AR differs in the three main subtypes of breast cancer (ER+, HER2+ and TNBC) and can change with treatment or disease progression. For instance, ER+ primary breast cancers can increase expression of AR following treatment with anti-estrogens such as tamoxifen or aromatase inhibitors, such that recurrent disease (having been deprived of estrogen), is rendered more dependent on androgens and AR. In some TNBC, AR can substitute for ER to some degree, and such tumors are slower growing and therefore less responsive to chemotherapy and often overexpress HER2. These types of tumors may therefore be responsive to concurrent treatment with anti-androgen combined with chemotherapy or HER2 targeting agents, much as we do for ER+/HER2+ tumors. This lecture will summarize impactful preclinical studies and summarize results of recent and ongoing clinical trials targeting AR in breast cancer.
Citation Format: Richer JK. Androgen Receptor in breast cancer. When might it serve as a suitable target? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES9-1.
Abstract OT2-01-01: Observational study of axilla treatment for breast cancer patients with 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes
Authors: Imoto S , Saito Oba M , Masuda N , Nagashima T , Wada N , Takashima T , Kitada M , Kawada M , Hayashida T , Taguchi T , Aihara T , Miura D , Toh U , Yoshida M , Sugae S , Yoneyama K , Matsumoto H , Jinno H , Sakamoto J 
Published: February 2018

Abstract
[Background] Axilla surgery in node-positive breast cancer is dramatically changing from axillary lymph node dissection (ALND) to sentinel node biopsy (SNB). From the results of ACOSOG Z0011, IBCSG23-01 and AMAROS trials, adjuvant therapy and regional node irradiation could reduce regional lymph node recurrence for sentinel node-positive breast cancer patients. However, optimal indication of SNB alone remains uncertain. Trial design: To evaluate the outcome of sentinel node-positive breast cancer patients, the Japanese Society for Sentinel Node Navigation Surgery (SNNS) conducted a prospective cohort study in 2013 (UMIN000011782, Jpn J Clin Oncol, p.876-9, 2014). [Eligibility criteria] For eligible patients, SNB was performed or scheduled after 1 January 2012. Then 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes are confirmed by histological or molecular diagnosis. Primary chemotherapy before or after SNB is also acceptable for registration. [Specific aims] The primary endpoint is the 5-year recurrence rate of regional lymph node in patients treated with SNB alone. The secondary endpoint is the 5-year overall survival rate of this cohort. Patients treated with SNB followed by ALND are also registered simultaneously to compare the prognosis. The propensity score matching (PSM) is used to make the distributions of baseline risk factors comparable. [Statistical method] Based on an estimated recurrence rate of 5% at 5 years among patients treated with SNB alone, 240 patients are needed to give a 80% power to reject the null hypothesis that the recurrence rate is 10% with a one-sided type I error rate of 2.5%. If we consider that some patients will be lost to follow-up or become ineligible, a total of 250 patients will be needed to comprise the sample. [Present accrual] Eight hundred and eighty patients who underwent SNB alone or SNB followed by ALND were registered from 27 participating institutes between 2013 and 2016. Data cleaning is being performed. Patient's background and PSM will be reported.
Citation Format: Imoto S, Saito Oba M, Masuda N, Nagashima T, Wada N, Takashima T, Kitada M, Kawada M, Hayashida T, Taguchi T, Aihara T, Miura D, Toh U, Yoshida M, Sugae S, Yoneyama K, Matsumoto H, Jinno H, Sakamoto J. Observational study of axilla treatment for breast cancer patients with 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-01.
Abstract P1-01-03: Preclinical evidence that distant metastases occur via the lymphatic route
Authors: Leslie PL , Ghosh SK , Porrello A , Cooley BC , Pecot CV 
Published: February 2018

Abstract
Cancer that metastasizes beyond the lymph nodes is almost invariably terminal. Therefore, understanding how cancer metastasizes is a critical aspect to understanding and eventually preventing cancer spreading from tissue to tissue. A major question that remains controversial is whether cancer cells that metastasize to the LNs are able to physically leave the LNs to colonize distant tissues. Moreover, whether cancer cell metastasis between different tissues involves unique genes is a question that requires further research. Using the metastatic mouse breast carcinoma line 4T1 in an LN microinjection model, we provide evidence suggesting that cancer cells can indeed metastasize and colonize distant tissues after direct implantation into the LNs. Interestingly, direct comparison of distant tissue metastatic capability comparing LN-microinjected cells and tail vein-injected cells suggests that the lymphatic route of cancer cell spreading may be a more efficient mechanism of metastasis than the hematogenous route. Moreover, our comparative transcriptome analysis results suggest that LN metastases show unique gene expression profiles relative to the primary breast tumors and distant metastases. We identified several genes that are up- or down-regulated in an LN-specific manner and thus may play a role in metastasis to the LNs and beyond. Collectively, our results suggest that LN metastases constitute an active “staging site” from which breast cancer cells can further metastasize to distant sites. Furthermore, we identify a unique set of genes that may be involved in the breast cancer metastatic process, several of which are potentially targetable using currently available inhibitors.
Citation Format: Leslie PL, Ghosh SK, Porrello A, Cooley BC, Pecot CV. Preclinical evidence that distant metastases occur via the lymphatic route [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-03.
Abstract P1-03-12: The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment
Authors: Winikka L , Quach D , Harlow B , Brenner A , Munoz N , Tiziani S , deGraffenried L 
Published: February 2018

Abstract
Background: Studies have shown that obesity is associated with a worse breast cancer prognosis. Besides the effect of different stages of diagnosis and co-morbidities, recent data from our published in vitro and retrospective studies suggests that this phenomenon may occur because the obese state promotes a more aggressive cancer phenotype through the cyclooxygenase (COX-2) pathway and its production of prostaglandin E2 (PGE2). The metabolization of omega-3 fatty acids decreases the production of PGE2, and have been shown to have potential benefit to cancer patients by decreasing inflammation-related signaling. Our previous clinical trial showed mixed results in the effect of omega-3 PUFA supplements on PGE2 production in post-menopausal obese women. This led us to the hypothesis that the ratio of omega-3 to omega-6 PUFAs have differential effects on cell types within the tumor microenvironment, impacting cancer cell phenotype.
Approach: In vitro experiments, including wound-healing assays to determine motility, and clonogenic assays to determine overall survival, were performed to determine if exposure to higher ratios of omega-6 to omega-3 fatty acids lead to a more aggressive cancer phenotype. MCF-7 breast cancer cells were treated with the following fatty acid ratios of omega-6 (arachidonic acid (AA)) to omega-3 (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)): 46:1, 20:1, 10:1, and 1.3:1. The wound-healing assays showed greater motility with higher ratios of omega-6 to omega-3 fatty acids conditions and the clonogenic assays showed greater survival with the higher ratios.
Conclusion: These data indicate that lowering ratios of omega-6 to omega-3 fatty acids may lessen the aggressiveness of breast cancer cells and be beneficial to some patients. Studies are on-going to investigate the impact of PUFA ratios on cancer cell phenotype directly, including proliferation and invasion, as well as the indirect effects from modulation of the other cells within the tumor microenvironment, including the macrophages and adipocytes.
Citation Format: Winikka L, Quach D, Harlow B, Brenner A, Munoz N, Tiziani S, deGraffenried L. The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-03-12.
Abstract P1-13-02: Withdrawn
Authors: Guarneri V , Dieci MV , Bisagni G , Brandes AA , Frassoldati A , Cavanna L , Musolino A , Giotta F , Cavazzini G , Garrone O , Bertone E , Cagossi K , Nanni O , Ferro A , Donadio M , Aieta M , Zamagni C , Piacentini F , Maiorana A , Ragazzi M , Cucchi MC , Querzoli P , Orsi N , Curtarello M , Urso L , Amadori A , Orvieto E , Vicini R , Balduzzi S , D'Amico R , Conte P 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P2-04-01: Withdrawn
Authors: Magnani L , Pruneri G , Patten DK , Corleone G , Győrffy B , Erdős E , Saiakhova A , Goddard K , Vingiani A , Shousha S , Pongor LS , Hadjiminas DJ , Schiavon G , Barry P , Palmieri C , Coombes RC , Scacheri P 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P2-11-17: Is post mastectomy radiotherapy contributive in pN0-1mi breast cancers patients? Results of a French multi-centric cohort
Authors: Forissier V , Tallet A , Cohen M , Classe J-M , Reyal F , Chopin N , Mazouni C , Gimbergues P , Daraï E , Colombo PE , Azuar P , Lambaudie E , Houvenaeghel G 
Published: February 2018

Abstract
Aim: To assess the value of Post-mastectomy radiation therapy (PMRT) in breast cancer patients with no or minimal lymph nodes involvement.
Materials and methods: We retrospectively analyzed a French multi-centric cohort of 4283 patients treated between 1980 and 2013, by mastectomy and axillary dissection with or without PMRT. Practices were analyzed according 3 treatment periods (1980-1999, 2000-2005; 2006-2013). The value of PMRT on loco-regional recurrence, disease-free survival, breast cancer specific survival and overall survival was assessed in pN0-1mi patients, using multivariate analyses (logistic regression and Cox model). It was subsequently assessed according to the number of clinicopathologic recurrence-risk factors, generating a prognostic index (f-PMRT index), in an attempt to isolate a pN0-1mi patients subgroup deriving benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index in the discrimination of patients with significantly different outcomes, as well as the value of PMRT in each c-PMRT prognostic group.
Results: PMRT was considered in more than half pN0-1mi patients of our cohort. Whereas matching pN0-1mi patients according to the number of clinicopathologic recurrence-risk factors led to isolate a higher-risk subpopulation (≥ 3 RR factors), PMRT had no significant impact on patients' outcomes, on multivariate analysis. Whereas the Cambridge-PMRT index had the potential to discriminate 3 patient populations with significantly different outcomes, its use did not help to the decision making for PMRT.
Conclusion: Despite a large cohort, we failed to isolate a subgroup of early breast cancer patients suitable for PMRT, in the absence of lymph node involvement.
Citation Format: Forissier V, Tallet A, Cohen M, Classe J-M, Reyal F, Chopin N, Mazouni C, Gimbergues P, Daraï E, Colombo PE, Azuar P, Lambaudie E, Houvenaeghel G. Is post mastectomy radiotherapy contributive in pN0-1mi breast cancers patients? Results of a French multi-centric cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-17.
Abstract P3-01-16: How hot is enough for accurate sentinel lymph node axillary staging in breast cancer?
Authors: Lee MH , Kang SH , Cho J 
Published: February 2018

Abstract
Purpose:
Sentinel lymph node (SLN) biopsy is a well-established procedure for staging of the axilla in early-stage breast cancer and has replaced axillary lymph node dissection as the standard of care in patients with clinically lymph node–negative axilla. No consensus exists about the number of sentinel lymph nodes (SLNs) that should be removed based on radioactivity counts in breast cancer, although the “10% rule” is often used. In order to determine the frequency with which the hottest SLN 'fails' to be pathologically positive, and to determine which criteria best define the radioactive lymph node to be removed, we reviewed and analyzed our cases in which more than one SLN was detected and where there was also at least one pathologically positive node.
Methods:
We retrospectively studied 1062 breast cancer patients who underwent lymphoscintigraphy by injection of radioactive colloid and SLN biopsy between 2006 and 2015, with intraoperative determination of radioactive counts of nodes by a gamma probe.
Results:
A total of 247 patients (23.3%) had more than 1 SLN removed (mean 2.29); 53 patients (21.5%) had nodal metastases. Of the node-positive patients, the hottest SLN was positive in 90.6% (48 of 53). The lowest radioactive count of a positive SLN was 32% of that of the hottest node.
Conclusions:
In our study, most positive SLNs had the highest radioactivity and the hottest lymph node was not the pathologically positive node only in 9.4 %. Our institutional experience indicates that to obtain an acceptable false-negative rate, nodes should be removed until the 10% rule is met.
Citation Format: Lee MH, Kang SH, Cho J. How hot is enough for accurate sentinel lymph node axillary staging in breast cancer? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-16.
Abstract P3-03-05: Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype
Authors: Tredan O , De Talhouet S , Peron J , Friedlaender A , Vuilleumier A , Viassolo V , Ayme A , Chappuis PO , Buisson A , Bonadona V , Bodmer A , Labidi-Galy SI 
Published: February 2018

Abstract
Background:
Germline mutations in BRCA1/BRCA2 genes increase the risk of breast and ovarian cancers. In ovarian cancer patients (pts) treated with platinum, BRCA1, and especially BRCA2, carriers have better survival than non-carriers. In breast cancer pts, BRCA1 carriers have higher response rate to neoadjuvant chemotherapy, however the benefit on survival remains unclear.
Patients and Methods:
A cohort study was conducted in France and Switzerland and consisted in 860 pts diagnosed with early breast cancer who underwent genetic screening for BRCA1/BRCA2 germline mutations and who received neo(adjuvant) chemotherapy. Disease-free survival (DFS) and Breast-cancer specific survival (BCSS) were analyzed according to BRCA1/BRCA2 mutations and breast cancer subtype (triple negative breast cancers (TNBC) vs non-TNBC).
Results:
One hundred and forty-three pts carried BRCA1 mutation; 88 had BRCA2 mutation; and 629 were non-carriers. Median age at diagnosis was 39 years; median follow-up was 4.8 years. Two hundred and fifty-three pts had TNBC (94 BRCA1, 14 BRCA2 and 145 non-carriers), and 607 had non-TNBC (49 BRCA1, 74 BRCA2 and 484 non-carriers). Among TNBC pts, BRCA2 mutations were associated with higher 5-years DFS (100% vs 71% for non-carriers and 80% for BRCA1 carriers; log-rank p=0.040), and BCSS (100% vs 78% for non-carriers and 92% for BRCA1 carriers; log-rank p=0.011). BRCA1 mutations were associated with higher 5-years DFS compared to non-carriers, but the association did not reach statistical significance (HR adjusted on nodal status=0.64; 95%CI 0.36-1.16, Wald test p=0.14). BRCA1 mutations were associated with an improved 5-years BCSS compared to non-carriers (HR adjusted on nodal status=0.38; 95%CI 0.16-0.87, Wald test p=0.022). In non-TNBC patients, BRCA1 or BRCA2 mutations were not associated with higher 5-years DFS (79% for BRCA1, 79% for BRCA2 carriers, and 80% for non-carriers; log-rank p=0.88) nor BCSS (94%, 92%, and 94% respectively; log-rank p=0.79).
Conclusions:
Among pts with TNBC, having BRCA germline mutation was associated with improved survival. In our cohort of TNBC pts, BRCA2 carriers did not present breast cancer relapse.
Citation Format: Tredan O, De Talhouet S, Peron J, Friedlaender A, Vuilleumier A, Viassolo V, Ayme A, Chappuis PO, Buisson A, Bonadona V, Bodmer A, Labidi-Galy SI. Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-03-05.
Abstract P3-06-04: Bcl-2 functional converters inhibit tumor growth and metastatic potential in zebrafish xenografts
Authors: Gamble J , Pearce M , Kopparapu P , Jang HS , Tanguay R , Greenwood J , Kolluri S 
Published: February 2018

Abstract
While potential therapies might have pronounced success in the simplified settings in cell culture medium, many drugs fail or underperform when cancer cells are encased in a complex 3D microenvironment. Although, rat and mouse models will continue to be the gold standard for in vivo data in drug discovery, zebrafish xenograft models have emerged as a powerful model that can quickly and efficiently deliver in vivo drug efficacy data before commitment to expensive and time consuming rodent models. We have discovered several compounds that work as B-cell lymphoma 2 (Bcl-2) functional converters and activate Bcl-2 into a killer instead of its native anti-apoptotic role. In this study, we use a zebrafish xenograft model to evaluate the ability of these compounds to inhibit xenograft tumor growth of Bcl-2 expressing cancer cells, including triple negative breast cancers. Live fluorescent imaging of cancer cells within zebrafish embryos revealed a decrease in cancer cell growth while under treatment of compounds. Furthermore, the agents that converted Bcl-2 into pro-apoptotic protein also inhibited the metastatic potential of the cancer cells. Therefore, this study demonstrates zebrafish xenograft techniques that can be used to quickly and efficiently obtain in vivo drug discovery data. Moreover, we report novel Bcl-2 functional converter compounds that can effectively reduce xenograft tumor growth and its ability to invade tissue in a living 3D environment and establish the role of Bcl-2 in cancer progression.
Citation Format: Gamble J, Pearce M, Kopparapu P, Jang HS, Tanguay R, Greenwood J, Kolluri S. Bcl-2 functional converters inhibit tumor growth and metastatic potential in zebrafish xenografts [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-06-04.
Abstract P3-08-09: Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area
Authors: Schreuder K , Kuijer A , Rutgers EJTh , Smorenburg CH , Van Dalen T , Siesling S 
Published: February 2018

Abstract
Purpose
In Dutch guidelines gene expression profiles (GEP) are indicated in estrogen receptor positive early breast cancer patients in whom benefit of chemotherapy (CT) is controversial based on traditional prognostic factors alone. Aim of the current study is to assess the use and impact of GEP on administration of adjuvant CT in breast cancer patients who have according to national guidelines a clear indication to either use or withhold adjuvant chemotherapy (clinical high or low risk).
Methods
Clinical low- and high risk patients, according to Dutch breast cancer guidelines, diagnosed between 2011-2014 were selected from the Netherlands Cancer Registry (NCR). Influence of GEP use and GEP test result on CT administration was assessed with logistic regression.
Results
Overall, 26,425 patients were identified; 4.8% of patients with clinical low- risk (444/ 9,354), 7.5% of the patients with a clinical high-risk (1,281/ 17,071) received a GEP. GEP use was associated with a significantly increased odds of CT administration in clinical low-risk patients (OR=2.12 95%CI: 1.44-3.11). In clinical high-risk patients GEP use was associated with a decreased frequency of CT administration (OR=0.55, 95%CI: 0.48-0.63). Adherence to the GEP result was higher in clinical high-risk patients with a discordant GEP result as compared to clinical low-risk patients with a discordant GEP result: 71.7% vs. 52.2%, respectively.
Conclusion
GEP is frequently used outside the indicated area and significantly influenced the administration of adjuvant CT, although adherence to the test-result was limited.
Citation Format: Schreuder K, Kuijer A, Rutgers EJTh, Smorenburg CH, Van Dalen T, Siesling S. Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-09.