bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-06-11: Understanding resistance mechanisms of PIK3a inhibition in breast cancer
Authors: Le X , Luo F , Treacy D , Wulf G , Garraway L 
Published: May 2016

Abstract
Breast cancer is the most common non-cutaneous cancer in women worldwide. PIK3CA is the most frequently mutated oncogene in all invasive breast cancers, with about one third of cases harboring activating mutations. Small molecule therapeutics targeting PI3K pathway has been developed and investigated for a decade. Everolimus (an mTOR inhibitor) is now successfully used in conjunction with hormonal therapy in patients with metastatic hormone-receptor positive breast cancers. Inhibitors of PI3Kα have shown promise as a single agent as well as in combination with hormonal therapies. The high rate of primary and acquired resistance; however, limits clinical usage of this class of drugs. There is an urgent need to understand the resistance mechanisms of PI3K inhibition and develop strategies to overcome the resistance in breast cancer. We took a genome-scale functional screening approach to identify resistance mechanisms to PI3K inhibition in breast cancer. We performed a whole-genome lentiviral open-reading frame (ORF) overexpression screen in a breast cancer cell line (T47D) in the presence of a PI3Kα inhibitor. We screened a total of 15,590 ORFs and identified 75 genes whose overexpression confers resistance to PI3K inhibition. Once we validate the hits, we plan to determine the mechanisms by which the genes confer resistance. We also plan to perform RNA-sequencing in patient samples with PI3Ka resistance to evaluate the clinical relevance of these genes and pathways.
Citation Format: Le X, Luo F, Treacy D, Wulf G, Garraway L. Understanding resistance mechanisms of PIK3a inhibition in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-06-11.
Abstract P3-07-10: The association between the expression of progesterone receptor and clinical benefit of adjuvant trastuzumab in estrogen receptor-positive and HER2-positive breast cancer patients
Authors: Lee HW , Ahn SG , Park JT , Yang BS , Park S , Jeong J , Kim SI 
Published: May 2016

Abstract
Background: Previous studies have shown that progesterone receptor (PR) status has a prognostic value in hormone receptor-positive breast cancer. In this study, we evaluated the clinical significance of PR status in estrogen receptor (ER)-positive and HER2-positive breast cancer.
Methods: We retrospectively analyzed the data of ER+ and HER2+ breast cancer patients who underwent surgery at Gangnam Severance hospital and Severance hospital from 2002 to 2012. We excluded patients who had a history of previous cancer, received neoadjuvant chemotherapy, did not received adjuvant chemotherapy, and had contralateral breast cancer or metastasis at diagnosis. A total of 346 patients were identified. Among them, 155 patients (44.8%) received adjuvant trastuzumab.
Results: At a median follow-up of 59 months, median disease-free survival (DFS) and overall survival (OS) were 56 and 59 months, respectively. The DFS and OS showed no difference according to PR status in overall patients. Then, these patients were categorized into two groups: ER+/HER2+/PR+ and ER+/HER2+/PR-. In ER+/HER2+PR+ patient, there was no difference of DFS or OS according to trastuzumab use. In ER+/HER2+/PR- patients, DFS was significantly better in patients who received adjuvant trastuzumab treatment compared to those who did not (p=0.009). We also analyzed influence of PR status on treatment outcome between patients who received adjuvant trastuzumab and those who did not. In patients who received adjuvant trastuzumab, there was no difference of DFS or OS according to PR status. However, in patients who did not receive adjuvant trastuzumab, ER+/HER2+/PR- patients showed worse DFS than ER+/HER2+/PR+ patients (p=0.006).
Conclusions: In patients with ER+/HER2+ breast cancer, we found that a prognostic value of PR only retained in those who did not receive adjuvant trastuzumab. Our findings suggest that the use of adjuvant trastuzumab may offer less clinical benefit for the patients with ER+/HER2+/PR+ breast cancer.
Citation Format: Lee HW, Ahn SG, Park JT, Yang BS, Park S, Jeong J, Kim SI. The association between the expression of progesterone receptor and clinical benefit of adjuvant trastuzumab in estrogen receptor-positive and HER2-positive breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-10.
Abstract P3-07-43: DNA methylation patterns correlating with outcome in patients treated with first-line bevacizumab for metastatic breast cancer
Authors: Gampenrieder SP , Rinnerthaler G , Weinhäusel A , Pulverer W , Hugnagl C , Hackl H , Romeder F , Monzo Fuentes C , Hauser-Kronberger C , Mlineritsch B , Greil R 
Published: May 2016

Abstract
Background: Biomarkers predicting response to bevacizumab containing therapy in breast cancer are of urgent need for a personalized treatment approach. DNA methylation is involved in regulation of angiogenesis and development of treatment resistance and could therefore provide predictive information for bevacizumab efficacy.
Patients and methods: A genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in FFPE specimen of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy (discovery set). Twenty-eight (78%) samples came from primary tumor and 8 (22%) from metastasis (2 lung mets., 1 pleural met., 1 liver met., 2 soft tissue mets., 1 ovarial met, 1 bone marrow infiltration). Based on progression-free survival (PFS) and breast cancer subtype (ER+ vs. triple-negative) patients were divided in responder (R) and non-responder (NR). By biostatistical methods differences in the methylation pattern between R and NR were detected. The 48 most interesting genes (e.g. because of there involvement in angiogenesis or carcinogenesis) showing a differential methylation status between R and NR are currently validated in two further metastatic breast cancer cohorts treated with (main set) and without bevacizumab (validation set), respectively. These validated results will be presented at the meeting.
Citation Format: Gampenrieder SP, Rinnerthaler G, Weinhäusel A, Pulverer W, Hugnagl C, Hackl H, Romeder F, Monzo Fuentes C, Hauser-Kronberger C, Mlineritsch B, Greil R. DNA methylation patterns correlating with outcome in patients treated with first-line bevacizumab for metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-43.
Abstract P3-07-68: Population-based validation study of Adjuvant! for primary breast cancer patients in the Netherlands
Authors: Siesling S , van Kleef JJ , Bretveld R , Groothuis-Oudshoorn CGM , van der Palen J , Jobsen JJ , Struikmans H 
Published: May 2016

Abstract
Background Adjuvant! is an online risk prediction tool that can support breast cancer patients and physicians in clinical decision-making regarding adjuvant systemic treatment. The aim of this study was to validate Adjuvant! on a Dutch population-based cohort of women diagnosed in 2003 and assess its calibration and discriminatory accuracy.
Methods All Dutch patients diagnosed with invasive primary breast cancer in 2003 in the Netherlands meeting the criteria of Adjuvant!; unilateral, unicentric invasive breast cancer, no evidence of metastatic or residual disease, pathologically staged I-III and no pT4 features, were included. Local treatment consisted of breast conserving therapy or ablative surgery and axillary staging. Adjuvant systemic treatment was given according to national guidelines. Patient, tumor and treatment characteristics were retrieved from the Netherlands Cancer Registry. Endpoints were ten-year overall survival, breast cancer specific survival and event free survival.
Findings A total of 8,195 patients were included. Out of all patients, 4,389 (53.6%) received some form of adjuvant systemic therapy. Throughout a ten-year follow-up, 2,156 (26.3%) patients died and 1,953 (23.8%) patients developed a recurrent disease (locoregional, distant or contralateral invasive cancer or DCIS). Ten-year observed overall survival was underestimated by -1.4% (95% CI -2.3 to -0.4, p=0.006), breast cancer specific survival was underestimated by -3.3% (95% CI -4.1 to -2.6, p&lt;0.0001) and event free survival was underestimated by -3.5% (95% CI -4.5 to -2.6, p&lt;0.0001). Discrimination was moderate for overall survival and breast cancer specific survival but poor for event free survival.
Interpretation Adjuvant! does not accurately predict breast cancer specific survival and event free survival in this Dutch population-based study. Dutch patients showed better ten-year survival rates than predicted by Adjuvant!. For specific patient groups, the model could be used to estimate overall survival. We conclude that Adjuvant! should be used with caution in clinical practice in the Netherlands but probably also in other countries and the US.
Citation Format: Siesling S, van Kleef JJ, Bretveld R, Groothuis-Oudshoorn CGM, van der Palen J, Jobsen JJ, Struikmans H. Population-based validation study of Adjuvant! for primary breast cancer patients in the Netherlands. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-68.
Abstract P3-09-04: Growth inhibitory effects of Cornus officinalis on a model for triple negative breast cancer
Authors: Telang NT , Nair HB , Wong GYC 
Published: May 2016

Abstract
Background: The triple negative breast cancer (TNBC) molecular subtype is characterized by the absence of estrogen receptor-α (ER-α), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expressions. TNBC is refractory to endocrine and to HER-2 selective therapy, while options for the treatment of choice involving high dose Anthracyclin/Taxol based conventional chemotherapy and/or small molecule inhibitor based targeted therapy are associated with systemic toxicity and acquired tumor resistance, leading to compromised efficacy. These limitations emphasize a need to identify efficacious non-toxic agents for secondary prevention/therapy of TNBC. Cornus officinalis (CO) is a Chinese herb of a nutritional nature in the form of a fruit. It is a major ingredient herb in some well-known Chinese herbal formulations for health management purposes. Growth inhibitory efficacy of CO in a model for ER positive Luminal A molecular subtype of clinical breast cancer is associated with abrogation of estradiol promoted growth via generation of anti-proliferative estradiol metabolites [Telang et al: Mol. Med. Rep. 5: 20-28, 2012].The present study examines the growth inhibitory effects of CO, and identifies possible molecular targets for its efficacy in a pre-clinical cell culture model for TNBC.
Experimental model, Herbal Extract and Biomarkers: The human mammary carcinoma-derived ER-α negative, PR negative and HER-2 negative MDA-MB-231 cell line represents the model for TNBC. Non-fractionated aqueous extract from CO represents the test agent. Anchorage dependent growth, anchorage independent (AI) colony formation, cell cycle progression, cellular apoptosis and relevant pathway specific mechanistic assays represent the biomarkers for efficacy.
Results: Treatment of MDA-MB-231 cells with CO extract induces substantial dose dependent cytostatic growth arrest (IC50:0.1%; IC90:0.5%), and strongly inhibits AI colony formation. Within the cytostatic range CO inhibits G1 to S phase transition leading to G1 arrest that is accompanied by decreased expressions of Cyclin D1 and p-RB. Cellular apoptosis induced by CO is associated with modulation of the BAX-BCL-2 pathway, and up-regulation of the pro-apoptotic Caspase 3/7 activity.
Conclusions: These data provide a mechanistic evidence for efficacy of CO as a naturally occurring nutritional substance in a cell culture model for TNBC. The present study validates a mechanism based approach to prioritize efficacious non-toxic herbal extracts for secondary prevention/therapy of the TNBC molecular subtype of clinical breast cancer.
Citation Format: Telang NT, Nair HB, Wong GYC. Growth inhibitory effects of Cornus officinalis on a model for triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-09-04.
Abstract P3-12-09: Neoadjuvant radiochemotherapy in breast cancer- A safe and effect method for patients
Authors: Matuschek C , Boelke E , Budach W , Audretsch W , Wollandt S , Speer V , Nestle-Krämling C 
Published: May 2016

Abstract
BACKGROUND:
Neoaduvant radiochemotherapy (NRT-CHT) is the standard of care for many solid tumors. It could be also an alternative option for treating patients with locally advanced non inflammatory breast cancer (LABC). Surgeons are afraid of wound healing problems and fear bad cosmetic results. The purpose of this investigation was to find out if there are any acute or late side effects in breast conserving and mastectomy patients after NRT-CHX.
PATIENTS AND METHODS:
From 1991 to 1998 a total of 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with a consecutive electron boost in 214 cases or - in case of breast conservation - a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was given prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. Also we investigated the acute side effects in 10 patients with NRT-CHX who were treated with this method from 2012-2015.
The cosmetic outcome was assessed by patient questionnaire, panel evaluation, and breast retraction assessment (BRA). Quality-of-life was investigated by EORTC QLQ-C30 and BR23 and acute and late radiation side effects by LENT/SOMA scale
RESULTS:
The long term results of 64 patients after breast conserving surgery and 152 patients after mastectomy were available. Most patients rated their overall cosmetics as excellent or good (94% breast conserving, 55.8% mastectomy). Patient and panel ratings on all cosmetic outcomes were similar between the two groups. After a follow up of 14-23 years we did not detect any grade III or IV fibrosis in any of our groups. The median BRA score after breast conserving surgery was 2.9 and the over-all quality of life (QLQ-C30) was rated "excellent" or good in 82%. Furthermore we did not detect any grade 3 or 4 acute side effects in our 10 patients who were recently treated with NRT-CHX.
CONCLUSION:
NRT-CHX is safe method and it is not associated with severe grade 3 or 4 acute or late side effects.
Citation Format: Matuschek C, Boelke E, Budach W, Audretsch W, Wollandt S, Speer V, Nestle-Krämling C. Neoadjuvant radiochemotherapy in breast cancer- A safe and effect method for patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-09.
Abstract P3-12-10: Overall survival in triple-negative breast cancers - Prognostic influence of type of surgery and adjuvant radiotherapy: A systematic review and meta-analysis
Authors: O'Rorke MA , Murray LJ , Bhoo Pathy N 
Published: May 2016

Abstract
BACKGROUND: Triple negative breast cancers (TNBC) are an aggressive, poorer prognostic tumour subtype which are negative for oestrogen, progesterone and human epidermal growth factor receptor 2 (HER-2) expression. Whilst the role of radiotherapy (RT) following breast conserving therapy (BCT) is widely accepted, there is no agreed consensus on the use of post-mastectomy RT, particularly in early-stage TNBC patients.
METHODS: Four electronic databases were searched from their inception to April 2015 including PubMed, MEDLINE, EMBASE and web of science. Observational studies investigating overall survival and locoregional/distant recurrence outcomes in women with TNBC according to type of surgery and radiotherapy receipt were included. Authors were contacted directly for further data. A random effects model was used to pool study effect estimates using mastectomy (MT) only patients as the reference group.
RESULTS: 8 studies including data from 3,456 patients were included. The median age and duration of follow-up was 54 years and 3.6 years respectively. The adjusted pooled hazard ratio (HR) and 95% confidence interval (CI) for overall survival comparing BCT and MT+RT to MT only was 0.52 (95% CI 0.31, 0.87; I2= 70.9%) and HR 0.60 (95% CI 0.38, 0.96; I2=41.5%) respectively. In subgroup analysis of MT+RT vs. MT alone, there was no significant interaction with early (T1-2, N0-1) vs. late stage (T3-4, N2-3) disease p=0.773 or age at diagnosis (&lt;40, 40-64, ≥65 years) p=0.320. 5 studies evaluated local regional recurrence. Comparing BCT and MT+RT to MT only, the pooled HR was 0.61 (95% CI 0.41, 0.92) and HR 0.83 (95% CI 0.55, 1.26) respectively, with low heterogeneity detected (I2 0.0%). 4 studies assessed distant metastases. The pooled HR comparing BCT and MT+RT to MT only was 0.88 (95% CI 0.62, 1.23; I2= 0.0%) and HR 1.95 (95% CI 0.85, 4.49; I2= 75.1%) respectively.
CONCLUSIONS: The addition of adjuvant radiotherapy appears to favourably impact overall survival, irrespective of the type of surgery received. BCT may reduce the risk of locoregional recurrence in comparison to MT only. The small number of contributing studies and often high study heterogeneity suggest cautious interpretation of the findings. Further epidemiological studies or pooled analyses of individual patient data are warranted.
Citation Format: O'Rorke MA, Murray LJ, Bhoo Pathy N. Overall survival in triple-negative breast cancers - Prognostic influence of type of surgery and adjuvant radiotherapy: A systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-10.
Abstract P3-12-17: Can radiation dosimetric parameters explain severe skin reaction during adjuvant whole breast irradiation applying field-in-field technique?
Authors: Yoon WS , Lee NK , Lee JA , Yang DS , Kim CY , Son GS , Chang YW 
Published: May 2016

Abstract
Aim: Although modern radiotherapy such as field-in-field technique decreased the radiation toxicity, skin reaction is still frequent and main problem during adjuvant whole breast irradiation. Our study investigated various radiation dosimetric and clinical parameters as the risk factors of severe skin reaction.
Methods: From January 2012 to December 2014, total 219 patients with breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients took both whole breast irradiation (50 Gy/25 fractions) and boost to the tumor bed (10 - 15 Gy). Skin reaction was measured by comparing the photography of radiation field between the first day of whole breast irradiation and boost therapy. For each axilla and inferior fold, the intensity (score 1 to 5) and extent (score 0 to 1) of erythema were recorded and summed. The severe skin reaction was defined as score 5 or 6. The relations of various radiation dosimetric parameters for radiotherapy planning, personal breast characteristics and clinical factors to severe skin reaction were evaluated using the Logistic regression tests.
Results: Total 75 (34%) and 57 (26%) patients showed the severe skin reaction to axilla and inferior fold, respectively. The variables of P &lt; 0.2 in univariate analyses including age, the body mass index, the breast height, the V100, the calculated point dose in radiation planning system, the breast separation, the field size, and the gradient of inferior fold entered the multivariate analyses. Age (P=0.013 (OR = 0.950, 95% CI 0.913 - 0.989)), the body mass index (P = 0.015 (OR = 1.123, 95% CI 1.023 - 1.233)), the calculated axilla point dose (P = 0.091 (OR = 1.064, 95% CI 0.990 - 1.142)), and the gradient of inferior fold (P = 0.073 (OR = 1.029, 95% CI 0.997 - 1.063)) were risk factors for severe axilla skin reaction, whereas age (P = 0.018 (OR = 0.948, 95% CI 0.907 - 0.991)) and the V100 (P &lt; 0.001 (OR = 1.005, 95% CI 1.003 - 1.007)) were for severe inferior fold skin reaction.
Conclusion: In addition to clinical factor and personal breast characteristics, the radiation dosimetric parameters such as calculated point dose and V100 could be another predictive factors of severe skin reaction.
Citation Format: Yoon WS, Lee NK, Lee JA, Yang DS, Kim CY, Son GS, Chang YW. Can radiation dosimetric parameters explain severe skin reaction during adjuvant whole breast irradiation applying field-in-field technique?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-17.
Abstract P3-13-02: Surcigal management of ipsilateral breast tumor recurrence
Authors: Kolben T , Schwarz TM , Goess C , Blume C , Degenhardt T , Engel J , Wuerstlein R , Ditsch N , Harbeck N , Kahlert S 
Published: May 2016

Abstract
PURPOSE
Approximately 10-15% of breast cancer patients treated by breast conserving surgery (BCS) and adjuvant radiotherapy (RT) will develop ipsilateral breast tumor recurrence (IBTR).
International guidelines suggest total mastectomy as treatment of choice for IBTR following lumpectomy and RT. Nevertheless, there is evidence that second BCS might be equally sufficient.
PATIENTS AND METHODS
Patients with IBTR diagnosed between 1990 and 2014 after BCS and RT were included (n=170).
34.1% women underwent secondary BCS, whereas 65.9% were treated by mastectomy. We determined predictive factors for time to local progression (TTP), disease free survival (DFS), and overall survival (OS) comparing these two groups.
RESULTS
Median follow-up after primary IBTR was 49 months (59 months for patients still alive at time of analysis). Five-year IBTR-free rate after secondary BCS was 77.6% (SD±6.1%) and 75.0% (SD±4.5%) for patients after mastectomy. Five-year DFS was 57.3% (SD±8.2%), and 61.9% (SD±5.5%), five-year OS was 84.7% (SD±5.8%), and 72.6% (SD±5.1%), respectively.
Prior adjuvant systemic therapy, muscular invasion, and skin infiltration were independent significant risk factors for a shorter TTP.
Additionally, lymphovascular infiltration (LVI) in the IBTR increased the risk for a shorter DFS.
LVI, muscular invasion, and skin infiltration were identified as independent significant risk factors for a shorter OS.
CONCLUSION
No significant difference in local control, DFS, and OS was seen between IBTR patients treated either by secondary BCS or mastectomy. Our data suggest that secondary BCS for IBTR patients after initial BCS and RT is feasible in selected patients.
Citation Format: Kolben T, Schwarz TM, Goess C, Blume C, Degenhardt T, Engel J, Wuerstlein R, Ditsch N, Harbeck N, Kahlert S. Surcigal management of ipsilateral breast tumor recurrence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-13-02.