bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-16-17: Characterization of response to everolimus (EVE) in BOLERO-2: A phase 3 trial of EVE plus exemestane (EXE) in postmenopausal women with HR+, HER2- advanced breast cancer
Authors: Burris H , Gnant M , Hortobagyi G , Hart L , Yardley DA , Eakle J , Provencher L , Brechenmacher T , Saletan S , Taran T , Rugo H 
Published: August 2014

Abstract
Introduction: The BOLERO-2 trial demonstrated that combining the oral mammalian target of rapamycin (mTOR) inhibitor, EVE, with the steroidal aromatase inhibitor, EXE, more than doubled median progression-free survival (PFS) compared with placebo (PBO) plus EXE in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) breast cancer (BC) who relapsed or progressed following a nonsteroidal aromatase inhibitor (NSAI). Patients also achieved responses per Response Evaluation Criteria in Solid Tumors (RECIST) during treatment with EVE+EXE.
Methods: The phase 3, double-blind, BOLERO-2 trial randomized postmenopausal women with HR+ BC progressing or recurring after NSAIs in a 2:1 manner to EVE 10 mg once daily plus EXE 25 mg once daily (EVE+EXE; n = 485) or placebo (PBO) plus EXE (PBO+EXE; n = 239). The primary endpoint was PFS by local assessment. Overall response rate (ORR; complete + partial response per investigator assessment based on RECIST 1.0) and duration of overall response were secondary endpoints. In addition, best percentage change from baseline in sum of longest diameters of target lesions was assessed.
Results: At the time of final PFS analyses at 18 months’ median follow-up, ORR was significantly higher in the EVE+EXE arm compared with the PBO+EXE arm (12.6% vs 1.7%, respectively, by local assessment; P&lt;.0001). Among patients with measurable disease at baseline, 71% in the EVE+EXE arm had a decrease in the sum of longest diameters of target lesions compared with baseline vs 30% in the PBO+EXE arm. Median duration of overall response was 10.5 months (95% confidence interval [CI]: 8.2, 21.9 months) for EVE+EXE and 6.9 months (95% CI: 4.2, 6.9 months) for PBO+EXE. Of note, only 4 patients in the PBO+EXE arm had an objective response to treatment.
Conclusions: In addition to PFS, the combination of EVE plus EXE significantly improved ORR vs PBO+EXE in patients with HR+, HER2− advanced BC progressing during or after NSAI therapy. Furthermore, greater than two-thirds of patients treated with EVE+EXE experienced tumor shrinkage during treatment. These results further support the rationale for combining EVE with EXE to improve clinical outcomes in HR+, HER2− advanced BC progressing after NSAI therapy.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-17.
Abstract P3-01-03: Vitamin D levels at breast cancer diagnosis: Association with patient and tumor characteristics
Authors: Cate SP , Berger N , Boolbol SK , Klein P , Gillego A , Estabrook A , Malamud S , Chadha M , Lucido D , Shao T 
Published: August 2014

Abstract
Background: Despite many preclinical studies showing the anti-neoplastic effects of vitamin D on breast cancer, findings from epidemiologic studies and randomized trials remain inconclusive. It is possible that tumor heterogeneity in breast cancer may mask these associations. Variations in vitamin D metabolism may explain some racial disparities in breast cancer. We aimed to examine the association of serum vitamin D levels with individual patient and tumor characteristics.
Methods: We conducted an IRB approved retrospective chart review, identifying all breast cancer patients with documented pretreatment serum levels of 25-hydroxyvitamin D (25(OH)D) between February 2011-May 2013. The following clinical data were collected for each patient: age at diagnosis, ethnicity, menopausal status, tumor size (mm), lymph node status, estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Based on ER, PR, and HER2, patients were categorized into three molecular subtypes: 1) Hormone receptor (HR)+ (ER or PR positive, HER2 negative), 2) HER2+, and 3) triple negative (TN; ER, PR, and HER2 negative). Descriptive variables were analyzed using a one-way Anova test.
Results: Among the 200 breast cancer patients identified, the mean age was 55.9 years (range 29-90). Ethnicities of the patients were as follows: 104 (52%) Caucasian, 43 (22%) African American, 29 (15%) Hispanic, and 16 (8%) Asian. Seventy six patients (38%) were premenopausal, and 124 (62%) were postmenopausal. African Americans were found to have higher rates of triple negative tumors compared to all other ethnicities (24.4% vs. 11.6%, p = 0.029). Younger women had lower mean serum 25(OH)D levels compared to older women (p = 0.033). Lower mean 25(OH)D levels were seen in ER negative tumors compared to ER positive tumors (p = 0.0102). Mean 25(OH)D levels were lower in African American, Hispanic, and Asian breast cancer patients when compared to Caucasians (p = 0.0004). When stratifying by menopausal status, serum 25(OH)D levels differed more by tumor characteristics among premenopausal women than postmenopausal women. In premenopausal women, lower vitamin D levels were seen in patients who were African Americans (p = 0.0185), and with tumors that were ER negative (p = 0.0083). There was also a trend toward lower mean vitamin D levels in those with TN breast cancer compared to other molecular subtypes.
Conclusion: In premenopausal women, lower vitamin D levels were associated with African American race, younger age, and ER negative tumors. This may suggest that African Americans have defective vitamin D metabolism that may contribute to a more aggressive breast cancer phenotype. Further studies are warranted.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-01-03.
Abstract P3-01-04: Obesity induces functional transcriptomic changes enhancing the cancer hallmarks of estrogen receptor-positive breast cancer
Authors: Fuentes-Mattei E , Phan L , Velazquez-Torres G , Zhang F , Chou P-C , Shin J-H , Choi H-H , Chen J-S , Chen J , Gully C , Carlock C , Zhao R , Qi Y , Zhang Y , Wu Y , Esteva FJ , Lou Y , McKeehan WL , Ensor JE , Hortobagyi GN , Pusztai L , Symmans WF , Lee M-H , Yeung S-CJ 
Published: August 2014

Abstract
Obesity increases the risk of cancer death among postmenopausal women with estrogen receptor-positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon. Transcriptomic profiles of pretreatment biopsies from a prospective cohort of 137 ER+ breast cancer patients were analyzed. A transgenic and an orthotopic/syngeneic obese mouse models were created to phenocopy obese patients and evaluate the effect of obesity on breast carcinogenesis and tumor progression, and to explore further direct mechanisms. Functional transcriptomic analysis of untreated human ER+ breast cancer revealed that obesity was associated with increased insulin signaling among others. Many of the functional changes in obese patients were linked to cancer hallmarks. Obese mouse models recapitulated the functional transcriptomic landscape of obesity-associated changes seen in human ER+ breast cancer and demonstrated the role of the Akt/mTOR pathway in obesity-induced breast carcinogenesis and tumor progression. Functional transcriptomic analysis identified 85 biological functions common to humans and mice. An in vitro co-culture model revealed that adipocyte-secreted adipokines (e.g., TIMP-1) regulate adipocyte-induced breast cancer cell proliferation and invasion. The human transcriptomic data provided direct evidence for the roles of hyperinsulinemia, estrogen signaling, adipokine secretion, and inflammation in the link between obesity and ER+ breast cancer. Our animal experiments provide strong evidence for the causal relationship between obesity and accelerated carcinogenesis and cancer progression and for potential therapeutic interventions by blocking these signaling pathways.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-01-04.
Abstract P3-06-01: Association between metformin use and improved survival in breast cancer patients: A population-based study
Authors: Li YR , Tchou J 
Published: August 2014

Abstract
Background: Long-term use of AMP-kinase agonist Metformin, the first-line oral hypoglycemic agent, has recently been shown to be associated with both a decreased incidence of and improved survival following diagnosis of breast and other solid tumors. However, the sample size of most reported studies has been limited and has not been able to clearly delineate if there are molecular subtype-dependent effects.
Method: We implemented a population-based, retrospective case-control analysis of the effect of metformin on breast cancer outcomes. We comprehensively searched the electronic medical records of all female patients who were cared for within the University of Pennsylvania Health System between the years 1997 and 2013. To ensure the accuracy of patient selection, we focused our preliminary analysis on only patients (n = 20,684) who received an ICD9 code for breast cancer (BC) on at least 2 separate in-person visits. We assessed the use of metformin by identifying those patients who have at least a record of a metformin prescription both before the first breast cancer diagnosis ICD9 code and after the first breast cancer diagnosis visit. Overall survival was determined by assessing a combination of electronic medical record of patient expiration and the SSN Death Certificate Index. Statistical tests, including chi-sq and cox-hazard modeling were implemented in R, Graphpad Prism or EXCEL.
Results: In the preliminary analysis, we identified a total of 29,251 female patients either diagnosed or reported a history of BC within the UPHS EMRs. Stratifying by per patient visits, we limited the subsequent analysis to the 20,684 BC patients with at least 2 in-person visits where BC was recorded as a diagnosis code. Of these, there were 534 patients who had a record of metformin prescription prior to and after the first BC diagnosis code and 20,150 BC patients who did not. We found that with a mean follow up of (6.40 years), there were a total of 8 deaths (1.28%) in metformin users and 526 deaths (2.62%) among the no metformin users. Using a two-tailed chi-sq test, we found that metformin use was significantly associated with improved overall survival rates (98.50 vs 96.94%, p&lt;0.05). We are currently assessing the role of age, ethnicity, the presence of diabetes, health metrics related to insulin resistance, and the use of other metabolic regulators (insulin, sulfonylurea) using a cox-hazard proportional risk model.
Conclusion: Our preliminary analyses suggest that metformin use before and following diagnosis may be protective against overall mortality among women diagnosed with breast cancer. A more refined Cox proportional hazard modelling is ongoing, which will shed light on how factors such as the use of other metabolic agents, age, and breast cancer subtype may interact with metformin's effect on overall and disease-free BC survival.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-01.
Abstract P3-06-04: Differences in survival among women with primary and secondary metastatic breast cancer
Authors: Barinoff J , Schmidt M , Schneeweiss A , Hinke A , Schoenegg W , Henken S , Kutscheidt A , Pintoffl J , Jackisch C 
Published: August 2014

Abstract
Background
Retrospective analyses have shown survival differences in patients with primary metastatic breast cancer (PMBC) in comparison to patients with secondary metastatic breast cancer (SMBC). A subgroup analysis of 2,708 patients with metastatic breast cancer from two prospective non-interventional studies (NIS) allows exploring this hypothesis. The Her2-positive-NIS investigated trastuzumab therapy for Her2 positive metastatic disease additional to predominantly first line chemotherapy. The second NIS observed bevacizumab therapy for predominantly Her2 negative disease additional to chemotherapy as first- line option.
Methods
Information on PMBC or SMBC was available in 2,401 patients diagnosed with metastatic breast cancer and treated with targeted therapy between 2000 and 2011. Previously endocrine therapy in palliative status was allowed. Progression free survival (PFS) was defined as the time from the start of antibody therapy to disease progression or death; overall survival (OS) was defined as the time from the start of targeted therapy with antibody to death of any cause; PFS and OS were estimated by Kaplan-Meier product limit method.
Results
570 (24%) women had PMBC and 1831 (76%) had SMBC. Median follow-up was 23 months (range: 0.2 - 137). Median PFS in patients with PMBC and SMBC was 13.0 and 10.4 months, respectively (p = 0.0043); median OS for women with PMBC and SMBC was 33.5 and 28.5 months, respectively (p = 0.0023). 5 years after start of the study treatment 28% patients with primary and 23% with secondary metastatic disease were alive.
Conclusion
In a population of breast cancer patients treated with modern antibody therapies, woman with PMBC live significantly longer than those with SMBC. A possible explanation for this observation might be a negative selection process of patients suffering from secondary disease in spite of adequate primary treatment. Every fourth patients with metastatic breast cancer is a long survivor. The clinical-pathological characteristics and risk factors for this group are unclear. Prospective trials including translational investigations for these patient populations are needed.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-04.
Abstract P3-06-13: Transient increase in breast cancer risk after a full term pregnancy among African women
Authors: Sighoko D , Hou N , Ogundiran T , Adebamowo C , Ademola A , Ojengbede O , Anetor I , Akinleye S , Ndom P , Gakwaya A , Huo D , Olopade OI 
Published: August 2014

Abstract
Background
African women affected by breast cancer (BC) have high parity with five children or more, are relatively young at first full term pregnancy (FFTP), are diagnosed at a young age and are often premenopausal at diagnosis. While several studies have assessed the role of reproductive factors for BC risk among African women, none of them have assessed whether there is dual effect of age at full term pregnancy (FTP). In this communications, using a large dataset from an on-going hospital-based case-control study, we examine the role of age at full term pregnancy on breast cancer risk among African women.
Methods
The study includes sites in Nigeria (University College Hospital, Ibadan), Cameroon (Yaoundé General Hospital) and Uganda (Breast Clinic of Mulago Hospital of Kampala). It was initiated in 1998 in Nigeria and extended to Cameroon and Uganda in 2011. Cases were consecutive females diagnosed with invasive BC. Controls were recruited from the community or within the hospital and have never being diagnosed with any cancer. Cases and controls were aged 18 years or more and gave informed consent. Full term pregnancy was defined as a pregnancy that lasted at least 7 months and included both live birth and stillbirth. Logistic regression models were used to assess the effects of age at first and second FTP, and their interaction with current age on BC risk. Age at menarche, parity, body mass index and hormone contraception use were included in the models.
Results
The study includes 1668 cases and 2399 controls recruited between 1998 and May 2013. Mean duration of live birth was 9 months (SD±0.52) and 8.8 months (SD±0.66) for a stillbirth. Overall, the mean age at FFTP was 23 years (SD±4.91) for both cases and controls. Compared to nulliparous women, parous women who had FFTP at 20 years have increased risk (OR = 1.59, CI 95%, 1.16-2.21) to develop BC in the year following the pregnancy. Up to 5 years following the FFTP, this OR is 1.38 (CI 95%, 1.06-1.80) while it is 0.77 (CI 95%, 0.62-0.95) 25 years later. This observation was also true for parous women who have had their FFTP at 25, 30, or 35 years. Moreover, a similar pattern was observed when comparing uniparous women to women with 2 or more children.
Conclusion
Our results show a transient increase in risk of BC after a full term pregnancy which declined and became protective over time. This observation is consistent with the effect of pregnancy on BC that has been described in other populations and may partially explain the current profile of breast cancer among African women.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-13.
Abstract P3-06-18: The health of women study: A novel approach to the cohort study
Authors: Love SM , Sykes N , Fischetti CA , Sullivan-Halley J , Clague J , Bernstein L 
Published: August 2014

Abstract
PURPOSE: The purpose of the Health of Women (HOW) Study is to examine risk factors for breast cancer and factors that may contribute to long-term survivorship through an innovative online system that allows for participant engagement and data sharing with the research community.
METHODS: The HOW Study is conducted through online and mobile phone platforms. Questionnaires are developed in our custom built survey tool and are available for completion on the study's website. The system allows for automated skip patterns within questionnaires and collection of data directly into a SQL database. The cohort is open to anyone 18 years or older; recruitment sources include the Love/Avon Army of Women and the general public. Participants will be given the opportunity to pose questions they would like to see answered. The HOW Study is also a novel resource allowing outside researchers to submit questions to be incorporated into HOW questionnaires and creating a data sharing platform that facilitates researcher access to HOW data after an application process.
RESULTS: The HOW Study launched October 2012 and currently has 41,800 participants from across the nation and the globe. We have released 1 baseline questionnaire and breast cancer-specific questionnaires to capture diagnosis and treatment with greater than 90% completion rate for each.
CONCLUSION: We have shown that we can recruit and engage participants in an online cohort study. We believe that this study has the potential to transform epidemiologic research by engaging both participants and the research community. Our second baseline questionnaire will launch in the summer of 2013, which will give us the opportunity to increase enrollment and assess retention.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-18.
Abstract P3-07-11: Nipple aspiration fluid yielders and non-yielders: Genetic characteristics
Authors: Shidfar A , Wang J , Allu S , Scholtens D , Chatterton R , Khan S 
Published: August 2014

Abstract
Background: Nipple aspiration fluid (NAF) is a noninvasively acquired biosample that can provide a window of observation into the breast environment, but NAF yield is variable across studies, and is related to a variety of demographic and reproductive factors. We have recently observed a positive correlation between serum prolactin level and NAF yield status. The genetic traits determining NAF yield are unknown, but data from the 1970s linked wet type ear wax to NAF yield, and recent studies point to single nucleotide polymorphisms (SNPs) in the ABCC11 gene as a determinant of earwax type. Further, prolactin and prolactin receptor SNPs are related to serum prolactin level. We have investigated associations between NAF yield and SNPs in prolactin, prolactin receptor and ABCC11 genes in a recently completed case-control study.
Method: NAF and/or blood were collected from 916 women. Subjects were defined as yielder if NAF volume was equal or more than 2μL and non-yielder if it was less than 2μL. According to this definition, our subjects categorized as 557 yielders and 359 non-yielders. DNA was extracted from blood using Qiagen kit and 20 ng of DNA was used to amplify and genotype for ABCC11 (rs17822931), PRLR (rs37364), PRL (rs2244502), PRL (rs849872) SNPs using Taqman genotyping assay on an Applied Biosystems 7900HT machine.
Results: The median age of Yielders and Non-yielders was 51 and 54, respectively, with the same range of 31-70 for both groups (P&lt;0.0001). There were 209(38%) premenopausal, 257(46%) postmenopausal and 81(15%) perimenopausal of yielders vs. 99(28%) premenopausal, 229(64%) postmenopausal and 26(7%) perimenopausal of non-yielders (P&lt;0.0001). ABCC11 genotype distribution was significantly different between yielders and non-yielders (P = 0.00163). However, genotype distribution was not significantly different for PRLR (rs37364), PRL (rs2244502) and PRL (rs849872).
YNYTotalP (N vs. NY)ABCC11 (rs17822931)5413578980.00163CC437 (81%)269 (75%)706 TT5 (1%)16 (4%)21 CT99 (18%)72 (20%)171 PRLR (rs37364)5483599070.176GG89 (16%)43 (12%)132 TT272 (50%)181 (50%)453 GT187 (34%)135 (38%)322 PRL (rs2244502)5393588970.087AA73 (14%)32 (9%)105 TT233 (43%)155 (43%)388 AT233 (43%)171 (48%)404 PRL (rs849872)5433599020.102CC17 (3%)11 (3%)28 TT332 (61%)244 (68%)576 CT194 (36%)104 (29%)298
Conclusion: Our analysis demonstrates a correlation between ABCC11 (rs17822931) SNP and NAF yield status, with the major homozygous CC allele associated with NAF yielder and minor homozygous TT allele associated with non-yielder status. If NAF-based risk biomarkers are to be developed, a better understanding of the genetics of NAF yield is required.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-11.
Abstract P3-08-06: ROK study: Breast cancer survivorship cohort in Japan - Characteristics of 2,600 study participants
Authors: Mizota Y , Yamamoto S 
Published: August 2014

Abstract
[Background] Although there is growing epidemiologic studies to investigate the etiological role of lifestyle factors and psychosocial factors on female breast cancer, few studies have examined the effect of these factors on breast cancer prognosis. To investigate the influence of lifestyle factors and psychosocial factors on prognosis including the quality of life, recurrence and survival of patients with breast cancer, we designed a large-scale cohort study of breast cancer patients in Japan. In our study, lifestyle factors include diet, physical activity, and use of complementary/alternative medicine, psychosocial factors include hope, perceived positive changes such as growth from breast cancer, depression, support and so on.
[Methods] Our goal is recruiting 6,000 breast cancer patients. Main part of this study is being conducted as a collaborative study with three randomized clinical trials and one cancer registration. Participant's information on clinical factors, treatment, and follow-up will be obtained from the clinical trials and cancer registration. In addition, we started recruitment at National Cancer Hospital. A self-administered questionnaire will be delivered to participants before and every year (1 to 5 years) after surgery, and their responses will be employed as baseline data. At National Cancer Center Hospital blood samples and tissues are also to be collected. The primary endpoint is disease-free survival. The secondary endpoints are overall survival and the health-related quality of life. The follow-up period will be 5 years after the last participant enrollment. We will examine the association of lifestyle factors, psychosocial factors, biomarkers and genetic polymorphisms with the prognosis based on follow-up data.
[Results] Recruitment began in November, 2007, and as of March, 2013, 2,655 women have been enrolled along with 2,591 questionnaire data, 236 blood samples and tissues.
As it is now, approximately 50 women a month newly enrolled. Recruitment will be continued at least into 2018, the Rainbow of KIBOU Study will become one of the largest breast cancer cohorts in the world. In this presentation, we describe the study design and report baseline demographic among the study participants.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-06.