bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-05-01: Interactions between adipocytes and breast cancer cells stimulate cytokine production and drive Src/SOX2/miR-302b mediated malignant progression
Authors: Picon-Ruiz M , Pan C , Drewes-Elger K , Jang K , Besser A , Zaho D , Morata-Tarifa C , Kim M , Ince TA , Azzam D , Wander S , Cote RJ , Guy HA , El-Ashry D , Torne-Poyatos P , Marchal JA , Slingerland JM 
Published: February 2018

Abstract
Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. Obesity is a risk factor for many cancers, but the mechanisms by which it contributes to cancer development and patient outcome have yet to be fully elucidated. Here, we examined the effects of coculturing human-derived adipocytes with established and primary breast cancer cells on tumorigenic potential. We found that the interaction between adipocytes and cancer cells increased the secretion of proinflammatory cytokines. Prolonged culture of cancer cells with adipocytes or cytokines increased the proportion of mammosphere-forming cells and of cells expressing stem-like markers in vitro. Furthermore, contact with immature adipocytes increased the abundance of cancer cells with tumor-forming and metastatic potential in vivo. Mechanistic investigations demonstrated that cancer cells cultured with immature adipocytes or cytokines activated Src, thus promoting Sox2, c-Myc, and Nanog upregulation. Moreover, Sox2-dependent induction of miR-302b further stimulated cMYC and SOX2 expression and potentiated the cytokine-induced cancer stem cell-like properties. Finally, we found that Src inhibitors decreased cytokine production after coculture, indicating that Src is not only activated by adipocyte or cytokine exposures, but is also required to sustain cytokine induction. These data support a model in which cancer cell invasion into local fat would establish feed-forward loops to activate Src, maintain proinflammatory cytokine production, and increase tumor-initiating cell abundance and metastatic progression. Collectively, our findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of Src inhibitors for breast cancer treatment.
Citation Format: Picon-Ruiz M, Pan C, Drewes-Elger K, Jang K, Besser A, Zaho D, Morata-Tarifa C, Kim M, Ince TA, Azzam D, Wander S, Cote RJ, Guy HA, El-Ashry D, Torne-Poyatos P, Marchal JA, Slingerland JM. Interactions between adipocytes and breast cancer cells stimulate cytokine production and drive Src/SOX2/miR-302b mediated malignant progression [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 P6-05-01.
Abstract P6-07-05: Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of BRCA status and estrogen pathway
Authors: Benderra M-A , Zaoui M , Atlan M , Ferrand N , Denis JA , Leban M , Lamari F , Larsen AK , Sabbah M , Gligorov J 
Published: February 2018

Abstract
Prophylactic mastectomies are more and more frequent. As a result, breast reconstruction is also more frequent and mammary lipofilling often used to improve the aesthetic results. Contradictory cliniacal data have been published concerning the risk of breast cancer after using this technique. It is possible that Adipose-Derived Stem / Stromal Cells (ADSC or ASC), present in the lipofilling may interact with normal or tumoral epithelial mammary cells.
In this context, we studied the effect of conditioned media of human ASC on different tumor breast lines (MCF7, T47D, ZR75-1, SKBR3, SUM159). The ASCs were extracted from non-cancer patients with identical body mass index (BRCA1 and BRCA2 mutated or wild-type).
We observed that the conditioned media of ASC induced the proliferation of luminal, Her2 and basal-like tumor breast lines. This proliferative effect is more important when ASCs are differentiated and the BRCA mutation status has no impact on it. Finally, we have demonstrated an estrogen signaling within the ASCs which is set up during their differentiation. Differentiated ASCs express ERα and produce 17β-estradiol (E2). This estrogenic pathway seems to be established independently of the BRCA mutational status. The proliferative effect on luminal mammary lines induced by conditioned media of ASC could pass through this estrogenic signaling, but remains to be confirmed.
These data highlight the fact that adipose-derived stem cells in mammary lipofilling should only be used after a cancer has been eliminated, as there are still some uncertainties concerning their implication on carcinogenesis.
Citation Format: Benderra M-A, Zaoui M, Atlan M, Ferrand N, Denis JA, Leban M, Lamari F, Larsen AK, Sabbah M, Gligorov J. Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of BRCA status and estrogen pathway [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 P6-07-05.
Abstract P6-07-10: The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling
Authors: Faria M , Karami S , Granados-Principal S , Dey P , Verma A , Choi DS , Elemento O , Bawa-Khalfe1 T , Chang JC , Gustafsson J-A , Strom AM 
Published: February 2018

Abstract
Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that the variants of ERβ, namely ERβ1, ERβ2, ERβ4, and ERβ5, regulate aggressiveness of TNBC by regulating hypoxic signaling. RNA-seq of patient derived xenografts (PDX) from TNBC show expression of ERβ4 and ERβ5 variants in more than half of the samples. Furthermore, expression of ERβ4 in the immortalized, normal mammary epithelial cell line MCF-10A that is resistant to mammosphere formation caused transformation and development of mammospheres. By contrast, ERβ1, ERβ2 or ERβ5 were unable to support mammosphere formation. We have previously shown that all variants except ERβ1 stabilizes HIF-1α but only ERβ4 appear to have the ability to transform normal mammary epithelial cells, pointing towards a unique property of ERβ4. We propose that ERβ variants may be good diagnostic tools and also serve as novel targets for treatment of breast cancer.
Citation Format: Faria M, Karami S, Granados-Principal S, Dey P, Verma A, Choi DS, Elemento O, Bawa-Khalfe1 T, Chang JC, Gustafsson J-A, Strom AM. The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling [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 P6-07-10.
Abstract P6-08-18: Prognostic multigene testing in breast cancer: Patterns, disparities, and opportunities for advancing standardized patient care
Authors: Bernhardt EB , Caffrey AG , Celaya MO , Celaya V , Chamberlin MD , Rees JR 
Published: February 2018

Abstract
Background: The decision to give adjuvant chemotherapy to patients with hormone receptor positive early stage breast cancer is controversial given the overall good prognosis with local therapy (surgery and radiation) plus hormonal therapy alone. In 2004, the 21-gene RT-PCR assay recurrence score (Oncotype) was developed to stratify early stage patients into categories of high, low, and intermediate recurrence rates considering treatment with local and hormonal therapy alone. This was incorporated into the NCCN guidelines in 2008. We sought to compare NCCN guidelines to actual practice patterns.
Methods: By retrospective review, data were examined from eight state registries participating in the National Program of Cancer Registries' Comparative Effectiveness Research program: Alaska, Colorado, Florida, Idaho, Louisiana, North Carolina, New Hampshire, and Rhode Island. These were then compared to NCCN guidelines for prognostic multigene testing.
Results: Of the 28,372 cases examined, 18.6% were classified as carcinoma in situ, 39.6% were stage I, 24.3% were stage II, 9.1% were stage III, 4.9% were stage IV, and 3.6% were unknown stage. The overwhelming majority of cases, 75.5%, were estrogen receptor (ER) or progesterone receptor (PR) positive, while 15.7% were ER and PR negative, and 8.8% were hormone receptor unknown. Approximately 40% of cases were human epidermal growth factor receptor 2 (HER2) positive, and the remaining 60% were HER2 negative or unknown. Approximately 72% of patients were node negative or had unknown nodal involvement, while the remaining 28% had at least micro-metastatic nodal disease. Invasive ductal carcinoma was the most common histology accounting for 71.4% of cases examined. Median age was 62. Data analysis for the use of prognostic multigene testing in relation to NCCN guidelines, race, age, and the above clinical factors is on-going and will be presented at SABCS 2017.
Conclusion: The purpose of this study is to examine the factors associated with the use of prognostic multigene testing according to the NCCN guidelines, including personal and clinical factors. By identifying practice patterns we can then address disparities and opportunities for advancing standardized quality patient care.
Citation Format: Bernhardt EB, Caffrey AG, Celaya MO, Celaya V, Chamberlin MD, Rees JR. Prognostic multigene testing in breast cancer: Patterns, disparities, and opportunities for advancing standardized patient care [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 P6-08-18.
Abstract P6-08-26: Outcomes and prognostic factors in 2000 patients with TNBC: Long-term results covering 10 years
Authors: Morante Z , Pinto J , Enriquez D , Araujos J , Luque R , Eyzaguirre E , Saavedra A , Fuentes H , Neciosup S , Gomez H 
Published: February 2018

Abstract
Background: Triple-negative breast cancer (TNBC) is characterized by being a heterogeneous disease with different risk factors and poor survival rates. TNBC have a higher prevalence in the Peruvian population (21.3%) than in Caucasian groups. Our study aims to determine the outcome and identify prognostic factors in Peruvian women with TNBC.
Methods: We retrospectively analyzed TNBC patients treated at the “Instituto Nacional de Enfermedades Neoplasicas” between 2000 and 2014. Survival rates and differences were calculated by the Kaplan-Meier method and Log-rank test, respectively. With the Cox regression, in univariate and multivariate analysis, we identified prognostic factors in for our TNBC population.
Results: In total, 2007 patients were diagnosed.The mean age was 50 years (range: 19-95 years); 44.8% were premenopausal and 26.2% had obesity at diagnosis. A family history of breast and/or ovarian cancer was present in 266 (28.9%) patients. Regarding the clinical-pathological features, 1860 (93.5%) had ductal invasive carcinoma and 1024 (51.6%) patients were in Stage (S) III. Local relapse and distant metastasis affected to 34.5% and 51.4% of our patients, respectively. Lung (14.5%) and bone (9.7%) were the most frequent sites of metastasis. The median follow-up was 9 years. The 5 and 10 yrs DFS/OS rates are shown in table 1. In the multivariate analysis, adjuvant chemotherapy (ACT) (HR: 0.60, 95%CI: 0.44-0.82, p=0.001) and radiotherapy (RT) (HR:0.72, 95%CI:0.55-0.93, p=0.014) were associated with a reduced risk of recurrence, while nodal involvement were associated to a high recurrence risk. Factors associated to a reduction in the risk of death were ACT (HR:0.73, 95%CI:0.61-0.88, p=0.001), RT (HR: 0.70, 95%CI: 0.60-0.92, p&lt;0.001), and Neoadjuvant CT (HR: 0.61, 95%CI: 0.51-0.73, p&lt;0.001); in contrast, a NLR≥3 (HR:1.60,95%CI: 1.36-1.87, p&lt;0.001), N stage were associated with a higher risk of death.
Conclusions: Sociodemographic features of Peruvian patients with TNBC resemble other populations; however, our population is diagnosed at more advanced clinical stages, hence DFS and OS were lower than international reports while prognostic factors were similar to previous studies.
Table 1. 5- and 10-years DFS/OS ratesClinical StageIIIIIIIVTotalp (value)DFS (%) &lt;0.0015-years837540-63 10-years696429-52 OS (%) &lt;0.0015-years938239655 10-years837532550
Citation Format: De la Cruz-Ku G, Morante Z, Pinto J, Enriquez D, Araujos J, Luque R, Eyzaguirre E, Saavedra A, Fuentes H, Neciosup S, Gomez H. Outcomes and prognostic factors in 2000 patients with TNBC: Long-term results covering 10 years [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 P6-08-26.
Abstract P6-09-02: Associations between hereditary cancer panel predisposition genes and breast cancer histological subtypes
Authors: Lilyquist J , Laduca H , Hu C , Na J , Polley EC , Hart SN , Pesaran T , Tippin-Davis B , Goldgar DE , Dolinsky JS , Couch FJ 
Published: February 2018

Abstract
Background: Clinical panel testing has become routine practice for patients that are diagnosed with breast cancer at a young age and/or have a personal or family history of cancer. Associations with known breast cancer genes and breast cancer subtypes have been previously identified, such as BRCA1 associations with estrogen receptor negative (ER-) and triple negative (ER-/PR-/HER2-) breast cancers. However, the cancer predisposition genes associated with each of the four clinical subtypes of breast cancer have not been fully defined. We evaluated 24,901 Caucasian female breast cancer cases receiving clinical panel testing for 23 cancer predisposition genes and assessed associations between mutations in each gene and breast cancer subtypes.
Methods: Germline hereditary cancer multigene panel testing results for cancer predisposition genes were obtained for 24,901 Caucasian female breast cancer cases evaluated by a clinical testing laboratory. Information on tumor histology, personal and family history of cancer, age at diagnosis, and previous genetic testing was provided by clinical care providers of patients receiving clinical cancer genetic testing. Breast cancer cases were classified into clinical breast cancer subtypes based on estrogen/progesterone hormone receptor status (HR) and HER2 status: Luminal A (HR+/HER2-), Luminal B (HR+/HER2-), HER2 subtype (HR-/HER2+), and Triple Negative (HR-/HER2-). The frequency of pathogenic or likely pathogenic mutations observed in each subtype was compared against the Exome Aggregation Consortium (ExAC) non-TCGA non-Finnish European population to estimate risks.
Results: ATM was associated with moderate risks (odds ratio (OR)&gt;2.0) of Luminal A, Luminal B, and HER2 subtypes of breast cancer, but was not associated with the Triple Negative subtype. PALB2 was associated with moderate risk for Luminal B subtype, but high risk (OR&gt;5.0) for Luminal A, HER2, and triple negative subtypes. TP53 was associated with high risks for Luminal B and HER2 tumors. NBN, MRE11A, and RAD50 were not associated with any subtype of breast cancer.
Conclusions: Identifying associations between inherited mutations (odds ratio (OR)&gt;2.0) and breast cancer subtypes can inform clinical risk management, treatment options, and therapeutic development efforts.
Citation Format: Lilyquist J, Laduca H, Hu C, Na J, Polley EC, Hart SN, Pesaran T, Tippin-Davis B, Goldgar DE, Dolinsky JS, Couch FJ. Associations between hereditary cancer panel predisposition genes and breast cancer histological subtypes [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 P6-09-02.
Abstract P6-11-07: Effectiveness and adverse events of DigniCap® scalp cooling system
Authors: Traub L , Brandi C , Khandan F , Thill M 
Published: February 2018

Abstract
Background
Chemotherapy-induced alopecia (CIA) is able to affect a patient's self-image and confidence negatively. A decade ago scalp cooling failed to avoid chemotherapy- induced hairloss in women who underwent chemotherapy as only thermal packs were used.
The DigniCap® scalp cooling system consists of a silicon cap that includes two sensor controlled cooling cycles. These cycles regulate the scalp temperature to lead to a continuous vasoconstriction in the scalp. Thus, it is indicated to reduce the likelihood of CIA.
Reduced temperature results in a reduced blood flow to the scalp area so that less chemotherapy reaches the hair cells. Therefore, these are not exposed to the full dose of chemotherapy and may be able to survive the treatment.
The purpose of this study was to evaluate the effectiveness and adverse events of DigniCap® scalp cooling system.
Patients and Methods
Since October 2015, 48 of 60 planned breast cancer patients undergoing chemotherapy were prospectively included in a unicentric cohort study in the certified breast cancer center at AGAPLESION Markus Hospital, Frankfurt, Germany. The average age of the women was 52.7 years (range 33 – 76).
The chemotherapy regimen included 4x EC q3w -&gt; 12x paclitaxel q1w (60.4%), 4x TC q3w (8.3%), 6x carboplatin plus paclitaxel q3w (8.3%), 6x docetaxel, carboplatin, trastuzumab (TCbH) q3w + pertuzumab (4.1%), 4x nab-paclitaxel m 3 q4 (2.1%), 4x paclitaxel q2w -&gt; 4x EC q2w (2.1%), 18x paclitaxel q1w (2.1%), 18x paclitaxel q1w plus myocet q1w (2.1%), eribulin d1, 8 q3 (2.1%), 4x EC q3w -&gt; 12x paclitaxel q1w plus trastuzumab plus pertuzumab (2.1%), 6x carboplatin plus paclitaxel q3w plus bevacizumab (2.1%), 4x nab-paclitaxel3 q4 plus bevacizumab (2.1%), 4x nab-paclitaxel 3 q4 -&gt; 4x EC q3w (2.1%).
Our aim was to quantify the grade of alopecia, satisfaction and side effects of the scalp cooling system. Alopecia quantification was done by a standardized questionnaire and photo documentation. Final results of the whole cohort of 60 patients will be presented at SABCS 2017.
Results
The interim analysis showed a success rate of complete hair loss avoidance of 8.0%. Hair loss of less than 20% was documented in 60.0% (29 patients). In 19/ 48 patients (39.6%) adverse reactions caused by the DigniCap® Scalp Cooling System, like headache (12.5%) or CIA (27.1%) were reported.
Conclusion
Our evaluation shows that DigniCap® Scalp Cooling Systemhas a minimal rate of adverse events (39.6%) and reduces the likelihood of chemotherapy-induced alopecia (&lt; 20% hair loss)effectively by 60.0%, even in anthracycline-based regimen.
Citation Format: Traub L, Brandi C, Khandan F, Thill M. Effectiveness and adverse events of DigniCap® scalp cooling system [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 P6-11-07.
Abstract P6-12-03: Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema
Authors: Kaufman D , Shah C , Vicini F 
Published: February 2018

Abstract
Background: With improved breast cancer outcomes, an increasing focus on sequelae of treatment as part of survivorship has emerged. Breast cancer related lymphedema (BCRL) represents one such sequelae. Increasing data and recent NCCN guidelines support the use of prospective BCRL surveillance to allow for early detection and intervention as a method to reduce chronic, irreversible BCRL. Therefore, this study was performed to evaluate the impact early detection and treatment of BCRL in breast cancer patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS).
Methods: From 8/2010 through 12/2016, 206 patients were evaluated with BIS as part of a prospective surveillance program.The protocol included pre-operative assessment with BIS as well as post-operative assessments with BIS at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with a compression sleeve for 4 weeks. For the purpose of this analysis, high-risk was defined as receipt of ALND, regional nodal irradiation, or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy.
Results: A total of 206 patients were analyzed, with a mean age of 61 years old and a median follow up of 25.9 months. Overall, 17% of patients had least one high-risk feature, 8% had two factors, and 7% had all three factors. A total of 21 patients (9.8%) were diagnosed with subclinical BCRL. Increased rates of subclinical BCRL were seen in patients undergoing ALND (23% vs. 7%, p=0.01) with ALND and receipt of RNI associated with development of subclinical BCRL. At last follow-up, no patients had persistent, chronic BCRL following early, conservative intervention measures.
Conclusions: The results of this study support prospective surveillance and early treatment utilizing BIS. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with a very low rate of chronic BCRL.
Citation Format: Kaufman D, Shah C, Vicini F. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema [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 P6-12-03.