bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-10-18: Factors associated with mammographic density in Japanese women
Authors: Uchida K , Ohashi H , Hiroko N , Mimoto R 
Published: February 2018

Abstract
Background: Increased mammographic breast density decreases the sensitivity and the specificity of mammography screening and is associated with a significant risk factor for breast cancer. No studies were identified that examined the impact of supplemental screening on breast cancer recurrence rates or mortality for women with dense breasts. The aim of this study is to examine factors associating with breast density in Japanese women.
Data sources and methods: We used mammography check-up participants (n=5159, women aged 40 years or older) between Apr 2014 and Mar 2017 as our baseline data. Using a self-administered questionnaire, data of life style were collected. Logistic regression was used to estimate the odds of having dense breasts by age, body mass index (BMI), alcohol consumption, smoking, parity, menopausal status, dysmenorrhea, hormone replacement therapy (HRT), family history of breast cancer, physical exercise, fried foods intake, brightly colored vegetables intake, coffee intake, tea intake and bone mineral density. Breast densities were divided into four categories based on BI-RADS classification. BI-RADS 3 and 4 were defined as dense breast. All statistical tests were two-sided.
Results: Dense breast accounted for 62.3% of mammography screening participants. Dense breast at an early age was more frequent as 78.0% in the 40's. Alcohol intake (20 g or more a day, OR=1.62, 0.026) in post-menopausal women showed statistically significant positive interaction with dense breast. Weak positive interaction was seen in bone mineral density&gt;80% (OR=0.63, 0.086, n=775). On the other, age (OR=0.97, &lt;0.001), BMI (OR=0.78, &lt;0.001), number of live birth (one; OR=0.77, &lt;0.030, two or more; OR=0.37, &lt;0.001) and post-menopause (OR=0.60, &lt;0.001) showed statistically significant negative interactions with dense breast.
Conclusion: Dense breast accounted for 62.3% of all participants. Dense breast was more frequent at early age as 78.0% in their 40's. Alcohol consumption and bone mineral density in post-menopausal women were positive interaction with mammographic breast density. On the contrary, age, BMI, number of live birth and post-menopause were negative interaction with mammographic breast density.
Citation Format: Uchida K, Ohashi H, Hiroko N, Mimoto R. Factors associated with mammographic density in Japanese women [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 P3-10-18.
Abstract P3-14-11: Comparative effectiveness of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis
Authors: Yokoe T , Hayashida T , Nagayama A , Seki T , Takahashi M , Takano T , Abe T , Kitagawa Y 
Published: February 2018

Abstract
Background
The optimal choice of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) needs to be clarified. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy (HEC).
Methods
Randomized trials that compared different antiemetic regimens were included from MEDLINE. Quality was assessed using the Cochrane risk-of-bias tool. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Data were pooled using random-effects models. We conducted indirect comparisons using network meta-analysis of a Bayesian model. The main outcomes were the odds ratio (OR) for overall complete response (CR [i.e., no emesis and no rescue]). Safety was assessed from the trial description. All statistical tests were two-sided.
Findings
We systematically reviewed 24 randomized control trials (12,104 participants), which compared 12 different antiemetic regimens. Palonosetron (PAL) 0·75 mg (PAL0·75) + dexamethasone (Dex); aprepitant (APR) + a serotonin-3 receptor antagonist (5HT3) + Dex; and APR + PAL (0·25 mg or 0·50 mg) + Dex were more favorable than the reference regimen (OR, 1·51; 95% credibility interval [95%CrI], 1·18-1·91; OR, 1·78; 95%CrI, 1·58-2·05; and OR, 2·28; 95%CrI, 1·66-3·18, respectively). The oral combination of netupitant and palonosetron (NEPA) was more effective than conventional regimens (OR, 2·39; CrI, 1·73-3·30). Olanzapine (OLZ)-containing regimens were apparently the most effective: the ORs of OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + APR + 5HT3 + Dex were 2·78, 2·58, and 4·98, respectively.
Interpretation
The regimens of PAL0·75 + Dex, APR + 5HT3 + Dex, and APR + PAL + Dex were more favorable in conventional regimens (i.e., regimens without NEPA or OLZ), which support the NCCN guideline strategy. NEPA could be a better choice than conventional regimens. OLZ-containing regimens could be an optimal choice; thus, more trials need to be accumulated.
Citation Format: Yokoe T, Hayashida T, Nagayama A, Seki T, Takahashi M, Takano T, Abe T, Kitagawa Y. Comparative effectiveness of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis [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 P3-14-11.
Abstract P3-15-03: Clinical benefit, toxicity, and cost of metastatic breast cancer drug therapies: Visualizing randomized and non-randomized evidence
Authors: Silberholz J , Vahdat L , Bertsimas D 
Published: February 2018

Abstract
Background: Given the rapidly expanding size of the clinical trial literature for metastatic breast cancer (MBC) clinical trials, oncologists need tools that enable them to efficiently review the settings and results of previous studies.
Methods: We searched the Cochrane Central Register of Controlled Trials and PubMed to identify clinical trials testing MBC drug therapies. Key eligibility criteria included &gt;90% of patients enrolled in trial having MBC, therapeutic clinical trials, and Phase II or III studies with at least 10 patients at a dosage level. From each study, we extracted information about clinical benefit and toxicity of drug therapies, and we further estimated the costs of all drug therapies. We built a web-based visualization tool that presents the results of all studies testing a given drug combination, stratified based on patients' receptor statuses and prior exposure to therapy. The tool presents both aggregate and study-level results, and reports both unadjusted study results and standardized results based on key patient characteristics in the study populations.
Results: We included 1,783 studies containing 2,549 treatment arms and 170,515 patients in the visualization tool. The tool reports information on 77 HER-2-directed therapies, 101 hormonal therapies, and 675 undirected therapies. The visualization tool has been made publicly accessible for patients and doctors to access at http://cancertrials.info.
Discussion: We believe this tool will make literature reviews significantly more efficient for oncologists, enabling them to better leverage insights from the clinical trial literature when making treatment decisions.
Citation Format: Silberholz J, Vahdat L, Bertsimas D. Clinical benefit, toxicity, and cost of metastatic breast cancer drug therapies: Visualizing randomized and non-randomized evidence [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 P3-15-03.
Abstract P3-15-04: Signalling pathways targeted by the YangZheng Xiaoji extract and the therapeutic implications in human breast cancer
Authors: Jiang WG , Ye L , Owen S , Ruge F , Martin TA , Sanders AJ , Gao G , Wei C , Wu Y , Davies E 
Published: February 2018

Abstract
Background. Yangzheng Xiaoji is a formulation of Chinese medicine and has been used in the treatment of solid cancer as an adjuvant to chemotherapy by reducing the side effects to the patient. There has been evidence to show that the medicine has a direct biological role in cancer cells. In the present study, we sought to investigate the potential effects of the medicine on breast cancer cells and in particular aimed to identify the key targets and molecular pathways contributing to the anti-cancer effect of the medicine.
Methods. Human breast cancer cell lines (BT549, BT20, MDA MB-231, MCF-7 and ZR 75-1) with varying invasiveness and receptor status were used. The soluble extract of Yangzheng Xiaoji, namely DME25 was used in the study. The effects of DME25 on the growth, toxicity and cellular migration were assessed. Signalling kinase changes were screened using kinase antibody array based array technologies. Kinases were also validated using phosphorylation based protein blotting.
Results. Of the five breast cancer cell lines tested, Yangzheng Xiaoji extract DME25 showed little cytotoxicity over a broad range of concentrations. However, DME25 were able to markedly reduce the migration of the panel of breast cancer tested, without being toxic. Triple negative cells responded in a similar fashion with other cells. It was also noted that the adhesion of these cells were also inhibited by DME25. Using a protein kinase array, it was shown that a number of kinase complexes were inhibited by the medicine, notable ones including EGFR family kinases (reduced by 35%), Janus protein kinases (JAK) (by 57%), and Ras-related C3 botulinum toxin substrate (Rac1 or CDC42 GTPase) (by 49%) and Ribosomal protein S6 kinases (RSKs) (by 52%). Given the clinical significance of RSKs in human breast cancer, we further evaluated the role of RSK and RSK inhibitors in DME mediated cell functions and have demonstrated that both in triple negative breast cancer cells and receptor positive breast cancer cell lines, DME25 was able to synergistically enhance the effect of RSK2 inhibitor, SL1010-1, on the both the cellular migration and cell growth.
Conclusion. Yangzheng Xiaoji has a broad and direct effect on the migration of breast cancer, an effect unrelated to hormone receptor status and independent of cytotoxicity. The medicine appears to target kinase pathway, particularly for the RSK kinases, suggesting an important clinical implication in the treatment of breast cancer.
Citation Format: Jiang WG, Ye L, Owen S, Ruge F, Martin TA, Sanders AJ, Gao G, Wei C, Wu Y, Davies E. Signalling pathways targeted by the YangZheng Xiaoji extract and the therapeutic implications in human 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 P3-15-04.
Abstract P3-15-05: Early breast cancer in the elderly: characteristics, therapy, and long-term outcome
Authors: Gal O , Ishai Y , Sulkes A , Shochat T , Yerushalmi R 
Published: February 2018

Abstract
Objective: The number of older adults diagnosed with breast cancer is increasing. However, data on breast cancer characteristics, treatment, and survival in elderly women are sparse.
Methods: The database of a tertiary cancer center was searched for all women aged &gt;65 years who were diagnosed with early breast cancer in 2004-2007. Patients were divided into two age groups: 65-75 years and &gt;75 years. Data on tumor, treatment and outcome parameters were compared.
Results: The cohort included 390 patients. The older group underwent more mastectomies but less axillary surgery or adjuvant systemic therapy. Median overall survival (OS) was 9.5 years in the older group and not reached in the younger group; the 8 year disease-free survival rates were 85% and 88%, respectively (p=0.27). Both age and tumor subtype had an effect on OS and recurrence rates (p&lt;0.001 for OS; p=0.16 for recurrence). The worst outcome was noted in women aged &gt;75 years with triple-negative (TN) disease.
Conclusion: Treatment approach was different between both age groups, despite similar tumor characteristics. TN subtype presented as the most aggressive disease in both age groups. Physicians should be alert to these findings and select treatment on a case-by-case basis.
Citation Format: Gal O, Ishai Y, Sulkes A, Shochat T, Yerushalmi R. Early breast cancer in the elderly: characteristics, therapy, and long-term outcome [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 P3-15-05.
Abstract P4-03-10: Clinical observation of lapatinib versus continued use of trastuzumab for trastuzumab-resistant HER2-positive advanced breast cancer
Authors: Yin Y , Li W , Huang X , Wang J , Fu Z , Li J 
Published: February 2018

Abstract
Objective: To compare the efficacy, adverse effects and survival of lapatinib versus continued use of trastuzumab for trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer.
Methods: Patients who began the regimen of lapatinib plus capecitabine (LC or LX) or trastuzumab beyond progression (TBP) between May 2013 and October 2016 were selected from the First Affiliated Hospital of Nanjing Medical University. All of their clinical data were recorded, including age, performance status, hormone receptor status, metastatic site, primary or acquired trastuzumab resistance, previous treatment and so on. They were followed up until death or April 30, 2017. The primary end point was progression-free survival (PFS). The efficacy and safety of the two regimens were evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, respectively. Data were analyzed by SPSS version 19.0.
Results: In total, 95 patients were identified, including 40 treated with LX and 55 with TBP. Median follow-up time was 16.0 months. There was no difference in objective response rate (ORR) and disease control rate (DCR) between the two groups. By the end of follow-up, median PFS was 6.3 months with LX and 7.1 months with TBP (P=0.676). In patients with primary trastuzumab resisitance, longer PFS was observed in LX group compared with TBP group [median PFS: 8.0 months vs. 5.3 months, hazard ratio (HR)=0.416, 95% confidence interval (CI): 0.177-0.981, P=0.038]. The incident rate of new brain metastases during treatment was 2.5% in LX group and 10.9% in TBP group, respectively (P=0.233). Both regimens showed similar outcomes in baseline brain metastases. Grade 3-4 adverse effects included diarrhea 7.5%(3/40) and hand-foot syndrome 12.5%(5/40) in LX group, along with leukopenia 18.2%(10/55), thrombocytopenia 9.1%(5/55) and nausea/vomiting 3.6%(2/55) in TBP group.
Conclusion: LX and TBP were similarly effective for patients with HER2-positive breast cancer progressing on prior trastuzumab-containing therapy. Both were well tolerated in general. Lapatinib tended to reduce the risk of disease progression in patients resistant to trastuzumab primarily. LX or TBP after local treatment appeared to show no difference in treating patients with brain metastases.
Citation Format: Yin Y, Li W, Huang X, Wang J, Fu Z, Li J. Clinical observation of lapatinib versus continued use of trastuzumab for trastuzumab-resistant HER2-positive advanced 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 P4-03-10.
Abstract P4-03-13: Combined estrogen receptor alpha and XPO1 targeting to overcome endocrine resistance
Authors: Madak Erdogan Z , Kulkoyluoglu E 
Published: February 2018

Abstract
The majority of breast cancer-specific deaths occur in women with recurrent, ERα (+), metastatic tumors that are initially responsive to endocrine therapy yet become endocrine-resistant. There is a critical need for novel therapeutic approaches to re-sensitize recurrent ERα (+) tumors to endocrine therapies. The objective of this study was to elucidate mechanisms of improved effectiveness of combined targeting of ERα and XPO1, a nuclear transport protein in overcoming endocrine resistance. Using Cignal Finder pathway profiling, Seahorse metabolic profiling and GC/MS whole metabolite profiling, we found that combination of 4-OH-Tamoxifen (4-OH-Tam) and Selinexor (SXR), a highly selective XPO1 inhibitor that is currently in clinical trials for leukemia and prostate cancer, inhibited Akt phosphorylation by changing the phosphorylation status and localization of the kinase. Since we observed dramatic changes in Akt activity, we hypothesized that metabolic pathways and consequently metabolic profile of breast cancer cells would change in the presence of 4-OH-Tam and SXR. These cells were more dependent on mitochondria for energy production. Their glucose and fatty acid dependency decreased in the presence of SXR and cells were more dependent on glutamine as the mitochondrial fuel source. We demonstrated that combined targeting of XPO1 and ERα rewires metabolic pathways and induce autophagy. Remodeling metabolic pathways to regenerate new vulnerabilities in endocrine-resistant tumors is novel, and given the need for better strategies for improving therapy response of relapsed ERα (+) tumors, our findings show great promise for combined targeting of ERα and XPO1 in the clinic to reduce cancer recurrences.
Citation Format: Madak Erdogan Z, Kulkoyluoglu E. Combined estrogen receptor alpha and XPO1 targeting to overcome endocrine resistance [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 P4-03-13.
Abstract P4-06-18: Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study
Authors: Lee E-S , Han W , Kim Y , Rhu J , Park JH , Kim K-E , Ju YW , Kim R , Lee H-B , Moon H-G , Noh D-Y 
Published: February 2018

Abstract
Background
The identification of individuals at elevated risk for hereditary cancers has allowed the development of consensus recommendations for cancer screening and prevention. The introduction of multigene panels may identify more individuals with breast cancer gene mutations than does testing for BRCA1/2 alone. Therefore, the multigenerational panel increase the need for genetic counseling suggesting preventive approach or cancer-specific screening to patients and family members. The rapid clinical introduction of multigene panel testing, however, have several issues such as low- to moderate-risk gene mutations and clinical recommendations. We collect the mutation results and clinical recommendations after testing with multigene panel and giving genetic counseling.
Methods
We had developed multigene panel consisted of 64 genes related to hereditary cancer through previous study and prospectively enrolled 104 individuals who were appropriate candidates for hereditary breast cancer evaluation. The patients were tested with 64-gene panel(Celemics) and results were provided by us 4˜10 weeks later. We checked the family history of cancer and made a pedigree before testing.
Result
Among 104 participants, 26 patients harbored deleterious mutations, most commonly in high to moderate-risk breast/ovarian cancer genes (BRCA1/2, BRIP, RAD51 and RAD51D), Lynch syndrome gene(MSH6) and other genes(FH, SPINK1). We recommended the cancer-specific screening and/or preventive approach for mutation-positive patients and suggested additional genetic test for the family members. Among them, 6 (23%) patients received Risk reducing procedures (Prophylactic mastectomy or oophorectomy) and most of them(19 patients(73%)) received cancer specific screening.
Conclusion
We demonstrate the use of multigene panel testing for hereditary breast cancer and will suggest the process of the genetic counseling including indication and results analysis with multigene panel testing.
Citation Format: Lee E-S, Han W, Kim Y, Rhu J, Park JH, Kim K-E, Ju YW, Kim R, Lee H-B, Moon H-G, Noh D-Y. Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center 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 P4-06-18.
Abstract P4-09-10: Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study
Authors: Ye F , Hu X , Shao Z 
Published: February 2018

Abstract
Background: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. Because of its lymphotropic nature at initial presentation, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC). The aim of this study was to identify risk factors accounting for its lymphotropic features and to develop a nomogram to predict the probability of lymph node involvement in IMPC.
Patients and Methods: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. Ethical approval of the study was granted by the Institutional Review Board of Fudan University Shanghai Cancer Center. Multiple logistic regression analysis was conducted. A logistic regression model was used to construct the nomogram in the training set and then validated in the validation set. Nomogram performance was quantified with respect to discrimination and calibration.
Results: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. The demographic characteristics were comparable within sets. Larger lesion, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95 percent confidence interval 0.692 to 0.777), demonstrating a good prediction performance. A calibration curve for the nomogram was plotted to evaluate the agreement between actual (observed) outcomes and expected probabilities. The slope of the calibration curve was close to 1, which indicated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, in which AUC was 0.734 (95 percent confidence interval 0.701 to 0.767).
Conclusions: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinical parameters was established, which could accurately predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients, especially in neoadjuvant settings.
Citation Format: Ye F, Hu X, Shao Z. Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based 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 P4-09-10.