bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-13: Mucin-2 (Muc-2) modulates the biology of breast cancer
Authors: Astashchanka A , Shroka T , Jacobsen BM 
Published: February 2018

Abstract
Background: Metastasis and therapeutic resistance are major issues in treating patients with breast cancer. Breast tumors that secrete mucus are generally resistant to chemotherapy. One type of secreted mucin, Mucin-2 (Muc2), is expressed in some breast cancers, but is absent in non-neoplastic breast tissue, suggesting that it plays a role in modulating breast cancer biology. Whether Muc2 expression correlates with breast cancer patient survival is controversial. Thus, the effects of Muc2 on the biology of breast cancer are largely unknown. This study examined the role of Muc2 in modulating breast cancer cell proliferation in vitro and in vivo, response to chemotherapy, and metastasis.
Methods: Two novel cell lines were developed from patient derived tumor xenografts. These two cell lines, BCK4 and PT12, both express high levels of Muc2. In order to modulate Muc2 levels in both cell lines, shRNA targeted to Muc2 (shMuc2) were compared to non-targeting control shRNA (shNT). Decreased expression of Muc2 was confirmed using immunoblotting. Proliferation in vitro was measured using the IncuCyte live cell imaging system and crystal violet staining. Response to chemotherapy was measured by examining apoptosis using cleaved-caspase 3 expression. BCK4 and PT12 cells with shNT or shMuc2 were grown as solid tumors in immunocompromised mice and tumor volume measured by caliper. BCK4 cells with high Muc2 (shNT) and low Muc2 (shMuc2) were labeled with luciferase and examined in an experimental metastasis model where total disease was monitored by IVIS imaging.
Results: Decreased Muc2 expression decreased proliferation in BCK4 and PT12 cells versus non-targeting control cells both in vitro and in vivo. Treatment with the chemotherapeutic Docetaxel induced minimal apoptosis in BCK4 control cells with high Muc2 however, apoptosis was significantly increased in BCK4 cells with reduced Muc2. In an experimental metastasis model, mice injected with BCK4 cells containing low Muc2 had decreased disease burden versus those injected with control cells with high Muc2. Endogenous Muc2 expression in wild-type BCK4 cells increased with addition of EGF and this effect was abolished by addition of the EGF-receptor inhibitor, Erlotinib.
Conclusions: Muc2 expression plays an important role in mediating proliferation, apoptosis and metastasis of breast cancer cells. These data suggest that Muc2 is important in controlling the biology of Muc2 positive breast tumors. In addition, Muc2 may be important in guiding treatment and predicting outcomes in breast cancer patients.
Citation Format: Astashchanka A, Shroka T, Jacobsen BM. Mucin-2 (Muc-2) modulates the biology of 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 P1-01-13.
Abstract P1-01-18: Disrupting interactions between human breast cancer cells, adipocytes, and macrophages
Authors: Vallega KA , Sang Q-XA 
Published: February 2018

Abstract
An increasing number of studies have found that other cells in the tumor microenvironment can influence tumor cells. Adipocytes, which were once thought to function only in energy storage, are now considered an active endocrine organ that secretes pro-inflammatory cytokines and proteases. In human breast cancer patients, invading tumor cells are surrounded by mature adipocytes. The breast cancer cells cause the adipocytes to undergo phenotypic changes and overexpress pro-inflammatory cytokines and matrix metalloproteinases (MMPs), such as MMP-3 and MMP-11. The presence of the changed adipocytes then increases the invasion capacity of breast cancer cells. Obesity is an important breast cancer risk factor. It causes changes to adipocytes and the surrounding microenvironment by invasion of macrophage cells. The effects of obesity-induced macrophage invasion have not been well characterized in the sector of breast cancer-adipocyte crosstalk. A novel 3D co-culture system was used to investigate how macrophage-induced inflammation can worsen this crosstalk, and what changes are involved in cytokine expression, adipocyte de-differentiation, breast cancer aggressiveness, and extracellular matrix (ECM) composition. When macrophage conditioned media was added to adipocytes and breast cancer cells in co-culture, the breast cancer cells showed increased cell proliferation and migration abilities. Experimental co-culture (adipocytes, breast cancer cells, macrophage conditioned media) showed almost twice the number of cells than the control co-culture (adipocytes, breast cancer cells, non-conditioned media). Interestingly, breast cancer cells alone in macrophage conditioned media did not show an increase in proliferation. This shows that macrophages may not affect breast cancer proliferation directly, as all three cell types are needed for increased proliferation of breast cancer cells. Introducing macrophages into this crosstalk also resulted in increased migration abilities. After 24 hours, breast cancer cells grown in experimental co-culture migrated further to close a wound than breast cancer cells grown in control co-culture. These results show that macrophages can affect adipocyte-breast cancer cell crosstalk. This may help explain why obese breast cancer patients have worse prognosis than non-obese breast cancer patients. Further investigation into these effects may identify targets to improve prognosis and abate breast cancer aggressiveness in obese breast cancer patients.
Citation Format: Vallega KA, Sang Q-XA. Disrupting interactions between human breast cancer cells, adipocytes, and macrophages [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 P1-01-18.
Abstract P1-02-02: FASN inhibition by TVB-3166 associates with breast cancer subtype
Authors: Gruslova AB , Chen C-L , Wang C-M , Elledge RM , Kaklamani VG , Lathrop K , Huang TH , Brenner A 
Published: February 2018

Abstract
Fatty acid synthase (FASN) is overexpressed in numerous tumor types, including breast carcinomas, and promotes changes in the genetic program controlling lipid biosynthesis. While inhibiting FASN appears to be an attractive therapeutic approach under development, the success of this approach may depend on the identification of tumor subtypes with specific metabolic requirements. Applying a comprehensive profile of circulating tumor cells (CTC) using canonical pathway gene sets, we identified a correlation of metabolic subtypes with breast tumor subtype. A lipogenic subtype is strongly associated with Luminal A subtype, whereas the glycolytic subtype associated with Luminal B tumors. The triple negative subtype was more heterogeneous and had the expression of both sets of gene. Such a difference in the metabolic profile may dictate differential sensitivity to inhibitors targeting de novo lipid synthesis, including FASN. This was supported by in vitro studies using selective FASN inhibitor, TVB-3166. Exposure to TVB-3166 over 14 days incubation in Advanced MEM with 1% charcoal-stripped FBS selectively inhibited growth and viability of Luminal A breast cancer cells, but had no effect on Luminal B subtype. This was further confirmed in short-term patient derived cultures. Mechanistic studies suggest that TVB-3166 quickly disrupts FA synthesis leading to the disruption of the lipid raft architecture and tumor cell death through an apoptotic mechanism. In conclusion, our findings highlight that success of targeting cancer metabolism directly may depend on identification of tumor subtypes with specific metabolic requirements.
Citation Format: Gruslova AB, Chen C-L, Wang C-M, Elledge RM, Kaklamani VG, Lathrop K, Huang TH, Brenner A. FASN inhibition by TVB-3166 associates with breast cancer 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 P1-02-02.
Abstract P1-02-08: Reprogramming glucose metabolism and energy production in breast cancer cells
Authors: Kim H , Dong J , Xu J , Li D , Zheng Z , Ye N , Zhang Z , Chen H , Zhou J , Shen Q 
Published: February 2018

Abstract
Most mammalian cells use glucose as a main fuel source. Glucose is metabolized via glycolysis to pyruvate, which enters the mitochondria and then generates ATP through Krebs cycle in normal condition. However, metabolism is characteristically reprogrammed and cancer cells or highly proliferative cells preferably generate ATP through lactate production by lactate dehydrogenase (LDH/LDHA), referred to as the Warburg effect or metabolic reprogramming toward aerobic glycolysis. Efficient control of energy metabolism is the key to maintaining metabolic homeostasis, and disturbance in energy balance provokes diseases such as obesity, diabetes and cancer. However, the mechanisms underlying efficient energy metabolic homeostasis and breast cancer development are poorly understood. HJC0152, a novel small molecule glucose metabolism modulator, was developed using structure- and fragment-based drug design strategies and molecular modeling techniques. Aggressively growing and metastatic breast cancer cells of triple-negative subtype (MDA-MB-231) treated with HJC0152 showed decreased activity and protein level of LDHA, which resulted in a decrease lactate production. In addition, these cells also exhibited decreased glucose uptake and HK2 protein level. Furthermore, the amount of intracellular ATP in MDA-MB-231 cells was significantly reduced. Our findings suggest that HJC0152 is capable of reprogramming caner metabolism by modulating glucose metabolism and ATP production. These results may provide a rationale to develop HJC0152 as an effective therapeutic for cancer and other metabolic diseases with aberrant glucose metabolism. In addition, HJC0152 can serve as a molecular probing tool for elucidating the key factors responsible for developing breast cancer and other metabolic diseases.This work was supported by Grants P50 CA097007, and P30DA028821 (JZ) from the NIH, CPRIT (JZ), John Sealy Memorial Endowment Fund (JZ), DFI Grants from MD Anderson Cancer Center (QS), Holden Family Research Grant in BC Prevention (QS), and NCI PREVENT Program HHSN26100002 (QS).
Citation Format: Kim H, Dong J, Xu J, Li D, Zheng Z, Ye N, Zhang Z, Chen H, Zhou J, Shen Q. Reprogramming glucose metabolism and energy production in breast cancer cells [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 P1-02-08.
Abstract P1-07-36: Outcomes and failure of primary endocrine therapy for operable breast cancer in the elderly: A regional North-east of England study
Authors: Thomas R , Rowell R , Crichton S , Cain H 
Published: February 2018

Abstract
Introduction
Primary Endocrine therapy (PET) to treat oestrogen receptor (ER) positive operable breast cancer in the elderly is used widely in the UK. A previous Cochrane analysis revealed its inferiority in long-term local control in comparison to surgery. As such, current guidance from the Society of International Geriatric Oncologists (SIOG) suggest that PET should be reserved for patients with a reduced life-expectancy (2-3 years) or for those considered unfit for surgery. Inaccurate assessment of life expectancy could lead to treatment failure which is potentially catastrophic for the patient.
The aim of this study was to evaluate treatment failures in elderly breast cancer patients treated with PET and to determine predictors of failure.
Methods
A retrospective observational study was performed on consecutive patients with ER positive early stage breast cancer treated with PET between 2005 and 2015 in the three breast units in the north east of England. The primary outcome measure was treatment failure and the secondary outcome measure was disease progression.
Results
488 patients were included with mean follow up 31 months (SD 23). 465 (95.2%) patients were started on Letrozole as their initial therapy. Overall, 206 patients were still alive with their disease controlled at the end of follow up, 219 had died with their disease controlled and 63 (12%) experienced treatment failure. Kaplan-Meier survival analysis predicted at 3 years 40% of patients to have died with controlled disease and 10% to have failed, leaving 50% living beyond this point with controlled disease. Regression analysis identified younger age [SHR 0.96 (95% CI 0.94 to 0.99) p 0.013], larger tumours [SHR 1.03 (1.01 to 1.06) p 0.015], grade 3 cancers [SHR 3.58 (1.93 to 6.63) p&lt;0.001] and axillary lymph node metastases [SHR 1.93 (1.06 to 3.52) p 0.030] were all independent predictors of treatment failure. Disease progression was reported in 86 (17.6%) of patients.
Conclusions
This is the largest retrospective series conducted evaluating PET treatment failure. Our comparably low rate of failure in comparison to that in the literature (12-85%) reflects good clinical acumen. Clear predictors of failure have been identified, which support previous analyses, further validating our results. Patients are able to live longer term (beyond 3 years) and maintain local disease control, which may represent a viable long-term treatment in the absence of risk factors for failure. Further work on our series is underway examining the effect of decision-making on PET outcomes.
Citation Format: Thomas R, Rowell R, Crichton S, Cain H. Outcomes and failure of primary endocrine therapy for operable breast cancer in the elderly: A regional North-east of England study [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 P1-07-36.
Abstract P1-13-09: Withdrawn
Authors: Ignatiadis M , Litiere S , Rothe F , Riethdorf S , Proudhon C , Fehm T , Aalders K , Forstbauer H , Fasching P , Brain E , Vuylsteke P , Guardiola E , Lorenz R , Pantel K , Tryfonidis K , Janni W , Piccart M , Sotiriou C , Rack B , Pierga J-Y 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P1-13-10: Adjuvant treatment of HER2+ breast cancer: Should trastuzumab be given sequentially or concurrently with chemotherapy?
Authors: Dackus GMHE , Jóźwiak K , Van der Wall E , Van Diest PJ , Hauptmann M , Siesling S , Sonke GS , Linn SC 
Published: February 2018

Abstract
Background
Human Epidermal growth factor Receptor 2 positive (HER2+) breast cancers have a high risk of recurrence in the absence of systemic treatment. The monoclonal antibody trastuzumab in combination with chemotherapy has significantly improved survival. Randomized trials have given trastuzumab both concurrently and sequentially with chemotherapy. To date, only one study reported a comparison between concurrent and sequential trastuzumab, with a numerically but not statistically significant benefit for concurrent use.
Our aim is to evaluate whether there is a difference in survival between patients who received trastuzumab sequentially to chemotherapy compared to concurrently with chemotherapy using data from the population-based, Netherlands Cancer Registry (NCR).
Methods
All women diagnosed in the Netherlands with a HER2+, TanyNanyM0 breast tumor between 2005 and 2007 who received both chemotherapy and trastuzumab were identified from the NCR.
Kaplan Meier survival estimates and Cox regression were used to compare recurrence free survival (RFS) and overall survival (OS) by trastuzumab sequence. Hazard ratios (HR) were adjusted for grade, pathological T-stage, pathological N-stage, estrogen receptor (ER), progesterone receptor, radiotherapy, hormonal therapy and ovarian ablation.
Results
A total of 1,849 patients were identified, with a mean follow-up of 7.8 years. Of these, 1,260 received concurrent trastuzumab and 589 sequential trastuzumab. Most tumors were grade 3, node positive and ER+. During follow-up 358 RFS events occurred, 231 in the concurrently treated patients compared to 127 in sequentially treated patients. Regarding OS, 290 deaths were observed, 188 deaths in concurrently treated patients compared to 102 deaths in sequentially treated patients, respectively.
OS and RFS were similar among sequentially versus concurrently treated patients (adjusted HR 1.11; 95% CI 0.87-1.42; P=0.420 and adjusted HR 1.15; 95% CI 0.92-1.44; P=0.209, respectively).
Conclusion
We observed no significant difference in OS and RFS between patients who received sequential trastuzumab compared to patients treated concurrently. Based on our results no recommendation can be made favoring either of the two treatment sequences for the adjuvant treatment of HER2+ breast cancer patients.
Citation Format: Dackus GMHE, Jóźwiak K, Van der Wall E, Van Diest PJ, Hauptmann M, Siesling S, Sonke GS, Linn SC. Adjuvant treatment of HER2+ breast cancer: Should trastuzumab be given sequentially or concurrently with chemotherapy? [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 P1-13-10.
Abstract P1-15-02: Benefit of adjuvant chemotherapy in disease-free survival for T1N0 triple negative breast cancer
Authors: Morante Z , De la Cruz-Ku G , Pinto J , Araujo J , Fuentes H , Enriquez D , Luque R , Eyzaguirre E , Saavedra A , Luján M , Neciosup S , Gomez H 
Published: February 2018

Abstract
Background: Although chemotherapy is not recommended in low-risk early breast cancer, triple-negative breast cancers (TNBC) have twice risk of recurrence despite an aggressive treatment. In this study we evaluated the role of chemotherapy in the outcome of T1N0 TNBC patients in terms of disease-free survival (DFS) and overall survival (OS).
Methods: We evaluated a retrospective cohort T1N0 TNBC patients diagnosed between 2000 to 2014 at the Instituto Nacional de Enfermedades Neoplasicas (Lima-Peru). Survival rates differences were assessed by Log-rank test and prognostic factors were identified using the Cox proportional hazards model.
Results: We identified 123 T1N0 TNBC patients. The median age was 51 years (range: 28-85), where 38.5% were premenopausal. Thirty-six (29.3%) were pT1a/b and 87 were pT1c (70.7%). ACT was administered more frequently in pT1c patients (74.7% vs 55.6%; P=0.036). Locoregional relapse and distant metastases rates were 8.3% vs 19.5% and 5.6% vs 16.1% for tumors pT1a/b and pT1c, respectively. The median of follow-up was 8.8 years. Independent prognostic factors were pT stage and treatment with ACT. In relation to pT stage, DFS rates were 97% vs 78% (at 5-years) and 97% vs 70% (at 8-years) for pT1a/b vs pT1c patients, respectively (HR=4.8; 95%CI:1.46-17.0; P=0.015). In the other hand, patients treated with ACT had a better outcome with DFS rates to 5-years of 86% vs 74% and 8-years of 81% vs 65% (HR: 0.41, 95%CI: 0.17-0.97, p=0.043). Our study had not statistical power to evaluate benefit of ACT in pT1a/b patients. In cases with pT1c tumors, treatment with ACT was the only factor associated with a better DFS (HR=0.29, 95%CI: 0.11-0.77, p=0.012). Because the low mortality in our cohort, OS was not evaluable.
Conclusions: Treatment with adjuvant chemotherapy reduces the recurrence risk in 71% among pT1cN0 TNBC.
Citation Format: Morante Z, De la Cruz-Ku G, Pinto J, Araujo J, Fuentes H, Enriquez D, Luque R, Eyzaguirre E, Saavedra A, Luján M, Neciosup S, Gomez H. Benefit of adjuvant chemotherapy in disease-free survival for T1N0 triple negative 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 P1-15-02.
Abstract P2-01-09: Circulating tumor cells (CTCs) in the venous drainage of the breast in patients with primary breast cancer
Authors: Hattori M , Nakanishi H , Yoshimura A , Adachi Y , Iwase M , Gondo N , Kotani H , Sawaki M , Yatabe Y , Iwata H 
Published: February 2018

Abstract
Background:
CTCs are shed from tumors and circulate in the peripheral blood after passing through the drainage vein. Axillary lymph node dissection (ALND) provides access to the lateral thoracic vein which flows directly into the axillary vein. In this preliminary study, we evaluated the feasibility of detecting CTCs in the peripheral blood and in the lateral thoracic venous blood for breast cancer patients who underwent ALND.
Methods:
From June 2016 to March 2017, breast cancer patients who underwent ALND in our institute were eligible for this study. A peripheral blood sample,10ml, was drawn just before the surgery or one day before the surgery. A lateral thoracic venous blood sample was taken from the resected breast just after resection. A blood sample of 0.2ml or more was necessary for CTC isolation. The CTCs in the peripheral blood before surgery (periCTC) and in the blood from the lateral thoracic vein of the resected breast (ltvCTC) were quantitatively examined by using a size-selective CTC isolation platform.
Results:
A total of 21 patients with median age 51 years (37-75) were enrolled to the study. Of the 21 patients, 38% were premenopausal, 52% had neoadjuvant chemotherapy. Fifty-seven percent were ER and/or PgR positive, 24% were HER2 positive. Fifty-seven percent were stage II disease and 43% were stage III. In 3 patients, we couldn't obtain sufficient blood samples from the lateral thoracic vein. Of the remaining 18 patients, we were able to obtain the median 0.5ml (0.2-2.0) blood samples from the lateral thoracic vein. CTCs were detected in peripheral blood in 15 patients (71%) and median periCTC count was 1 CTC/10ml (0-39). In lateral thoracic venous blood, CTCs were detected in all patients who had sufficient blood samples and the median ltv CTC count was 35.5 CTC/ml (2.5-370). In 5 of 6 patients whom CTCs in peripheral blood samples were not detected, CTCs could be detected in the blood samples from lateral thoracic vein.
Conclusion:
CTCs can be detected in the peripheral blood and in the blood from lateral thoracic vein in patients with localized breast cancer, and can be detected at a higher rate and at a higher concentration in the blood from lateral thoracic vein than in peripheral blood.
Citation Format: Hattori M, Nakanishi H, Yoshimura A, Adachi Y, Iwase M, Gondo N, Kotani H, Sawaki M, Yatabe Y, Iwata H. Circulating tumor cells (CTCs) in the venous drainage of the breast in patients with primary 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 P2-01-09.