bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-09-02: Early life residence, fish consumption and risk of breast cancer
Authors: Haraldsdottir A , Torfadottir JE , Valdimarsdottir UA , Aspelund T , Tryggvadottir L , Launer LJ , Harris TB , Gudnason V , Steingrimsdottir L 
Published: May 2016

Abstract
Introduction: Few studies exist on the effect of diet during different periods of life, on breast cancer risk later in life. Great differences existed in food consumption between the capital and rural areas in Iceland in the middle of the 20th century, with very high fish consumption in coastal areas.
Objectives: Our aim was to explore the effect of diet and residence during early life and midlife on breast cancer risk later in life.
Methods and data: We used data from the Reykjavik Study, a population-based Icelandic cohort of 10049 women born between 1907 and 1935, and examined the association of residence in early life, used as a proxy for dietary habits, and risk of breast cancer. To further explore this association, we also used food frequency data at different periods of life, including adolescence, from the AGES-Reykjavik cohort, a subgroup of the Reykjavik Study, established in 2002. Participants provided information on residence in early life. By linkage with the Icelandic Cancer Registry, information on breast cancer diagnoses was available throughout 2013. Adjustments were made for a series of potential confounders, including residence for dietary analysis.
Results: During a mean follow-up of 27.3 years, 744 women were diagnosed with breast cancer. We found a significant inverse association for breast cancer diagnosis among women who lived though the puberty period (20 years or more) in coastal villages compared with women residing in the capital area (HR = 0.74, 95% CI: 0.58, 0.94). In the subgroup analysis, we found that women with high fish consumption in midlife had lower risk of breast cancer in older age, compared with women with lower consumption, (OR = 0.60, 95% CI 0.38, 0,94). However, we did not observe a statistically significant association between high fish intake in adolescence and breast cancer (OR = 0.84, 95% CI 0.62 - 1.13).
Conclusions: Our results suggest that high fish consumption in early- to midlife may be associated with reduced risk of breast cancer.
Citation Format: Haraldsdottir A, Torfadottir JE, Valdimarsdottir UA, Aspelund T, Tryggvadottir L, Launer LJ, Harris TB, Gudnason V, Steingrimsdottir L. Early life residence, fish consumption and risk of 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 P3-09-02.
Abstract P3-12-03: Utilizing the genomically adjusted dose (GAD) to personalize radiotherapy in adjuvant breast cancer management
Authors: Ahmed KA , Venkat PS , Scott JG , Diaz RJ , Fulp WJ , Torres-Roca JF 
Published: May 2016

Abstract
Background: We have previously validated a multi-gene model of tumor radiosensitivity (RSI) with validation in multiple independent cohorts including breast, rectal, esophageal, head and neck, glioblastoma, and prostate malignancies. Utilizing the linear quadratic model and RSI, we derived an expression for the genomically adjusted dose (GAD) to model radiation dose effect for individual patients.
Methods: As RSI models the surviving fraction of cells at 2 Gy (SF2), we are able to derive a patient specific alpha. These terms were used in the linear quadratic model to calculate a GAD to model radiation effect and its association with local control. A higher GAD implies a higher predicted radiation therapy effect. Clinical and array-based gene expression were obtained from 75 ER negative patients from the Netherlands Cancer Institute (NKI) and the Institut Curie treated with breast conservation therapy.
Results: Median follow-up for all patients was 10 years with a median age of 42 years (range: 23-50 years). Adjuvant radiation dose to the whole breast was 50 Gy (range: 45-55 Gy). When assessing local recurrence on multivariate analysis, we found GAD to be a significant predictor of local recurrence when dichotomized at the median (GAD-low vs GAD-high Hazard Ratio (HR) 4.5; 95% CI 1.7-13.5; p=0.0031). GAD was also significant per unit change (HR 0.91; 95% CI 0.83-0.99; p=0.021). We then modeled GAD for an escalated dose up to 60 Gy and found an additional 48% of GAD-low patients could achieve a GAD-high with dose escalation.
Conclusions: We found GAD to be significantly correlated with local control following breast conservation therapy. Modeling dose escalation with GAD, we identified a select population of patients whom we hypothesize may benefit from genomically guided increased dose in the adjuvant setting. This population may represent a cohort for future clinical trial enrollment.
Citation Format: Ahmed KA, Venkat PS, Scott JG, Diaz RJ, Fulp WJ, Torres-Roca JF. Utilizing the genomically adjusted dose (GAD) to personalize radiotherapy in adjuvant breast cancer management. [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 P3-12-03.
Abstract P3-14-04: Effects of the dual selective CYP17 lyase inhibitor and androgen receptor (AR) antagonist, VT-464, on AR+ and ER+ tumor models in vitro and in vivo
Authors: Ellison SJ , Norris JD , Wardell S , Eisner JR , Hoekstra WJ , Stagg DB , Alley HM , Moore WR , McDonnell DP 
Published: May 2016

Abstract
VT-464 is a lyase-selective inhibitor of the dual-activity CYP17A1 enzyme that is required for the synthesis of androgens and estrogens in the gonads, adrenals, and tumors. In addition to its role as a CYP17A1 lyase inhibitor, we previously showed that VT-464 also functions as a direct and effective AR antagonist in prostate cancer models. In our current study, we evaluated the therapeutic potential of VT-464 in breast cancer by analyzing its effectiveness in several AR-positive breast cancer cell lines, including those that are ER-positive and ER-negative. Through in vitro assays and xenograft analysis, we compared the activity of VT-464 to enzalutamide, a second generation AR antagonist that is approved for the treatment of castration resistant prostate cancer and is in multiple Phase 2 breast cancer studies. Our results showed that VT-464 was highly effective in preventing proliferation of both ER-positive and ER-negative breast cancer cell lines in vitro. Importantly, significant inhibition was also observed in soft agar assays that assesses anchorage-independent growth. In mechanistic studies, VT-464 and enzalutamide both inhibited induction of AR target genes and recruitment of AR to target promoters, verifying direct AR antagonistic activity observed previously in prostate cancer cells. Furthermore, we evaluated the ability of VT-464 and enzalutamide to inhibit tumor formation in a tamoxifen-resistant model of breast cancer. Oral administration of either enzalutamide or VT-464 significantly decreased tumor growth in mice, with VT-464 achieving greater growth inhibition than enzalutamide. Together, these data provide further rationale for the future study of the AR as a viable therapeutic target in breast cancer, and importantly, suggest that AR inhibition can impact tamoxifen-resistant tumor growth. The dual effects of CYP17A1 lyase inhibition and AR antagonism that are achieved with VT-464 further supports its development as an effective oral therapy option for AR-positive breast cancer. A phase 1 / 2 clinical study of oral VT-464 in women with AR+ triple-negative breast cancer or ER+ cancer resistant to aromatase inhibitors will commence in 2015.
Citation Format: Ellison SJ, Norris JD, Wardell S, Eisner JR, Hoekstra WJ, Stagg DB, Alley HM, Moore WR, McDonnell DP. Effects of the dual selective CYP17 lyase inhibitor and androgen receptor (AR) antagonist, VT-464, on AR+ and ER+ tumor models in vitro and in vivo. [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 P3-14-04.
Abstract P4-02-09: Can MRI be used to determine pathological complete response following neo-adjuvant chemotherapy for breast cancer?
Authors: Sharma N , Dave R , Millican-slater R , Dodwell D , Horgan K 
Published: May 2016

Abstract
Intro
Neo-adjuvant chemotherapy (NACT) is increasingly offered to patients with breast cancer, and it understood that patients with pathological complete response (PCR) have improved survival. It has been suggested that patients with radiological complete response may be spared surgery. We aimed to determine whether MRI findings can predict PCR following NACT.
Methods
This was a retrospective analysis of a prospectively maintained database. Most patients had NACT with 6 cycles of EC/DC+/-Traztuzumab and response was monitored using MRI. For univariate analysis χ2 and Fisher's exact test was used for categorical data. Log rank test by Kaplan Meier method was used for survival analysis.
Results
310 patients had NACT from December 2007 to December 2014. Baseline MRI prior to embarking on NACT was achieved in 251 patients. MRI concorded with size on mammography/USS in the majority of cases (83%) and upgraded the overall size of the lesion in 16% (50% of unifocal lesions on USS upgraded to multifocal).
In the 247 patients who had baseline MRI, a radiological response seen on the 2nd MRI (early responders, n=138), was predictive of eventual PCR (p=0.000, sensitivity = 77%). Patients with Her2+ve non-luminal (65%), triple negative (TNBC) (64%) and Luminal B Her2-ve (65%) tumours were more likely to be early responders on MRI. The non-early responders with Her2+ve tumours all had late radiological response, however, the TNBC tumours had low rates of late radiological response. Complete radiological response on the final MRI correlated strongly with PCR; p=0.000, specificity=98%. Tumour vascularity correlated positively and significantly with PCR. There was no difference in survival between those with early and late radiological response (median survival 66.2 months and 66.9 months), but those with no radiological response had significantly poorer survival 53.2 months, p=0.012).
Conclusion
Response on MRI is predictive of PCR, particularly within the non-luminal Her2+ve and TNBC molecular subtypes. Early response has high sensitivity, and complete response on final MRI has high specificity. Further work on larger data-sets is required before we confidently spare patient from surgery in the event of complete response on MRI.
Citation Format: Sharma N, Dave R, Millican-slater R, Dodwell D, Horgan K. Can MRI be used to determine pathological complete response following neo-adjuvant chemotherapy for 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 P4-02-09.
Abstract P4-02-11: Value of magnetic resonance imaging in preoperative predicting tumor extent in each subtypes of breast cancer
Authors: Yang BS , Lee HW , Park JT , Lee HM , Ahn SG , Jeong J 
Published: May 2016

Abstract
Background: It is well known that patients with triple-negative breast cancer (TNBC) have a high risk of local tumor recurrence in ipsilateral breast. To know the additional value of breast magnetic resonance imaging (MRI) in preoperative prediction of tumor extent for TNBC, we tested the accuracy of MRI in correlation with pathologic tumor size according to subtypes. In addition, we investigated the margin-positive rates by subtypes among the patients receiving breast-conservative surgery (BCS).
Methods: We retrospectively identified patients with invasive breast cancer who had preoperative breast MRI and ultrasound between 2011 and 2014. We excluded patients having large tumor more than 5cm or multiple tumors. Patients were classified into 4 subtypes (luminal A, luminal B/HER2, HER2, triple-negative breast cancer (TNBC)) based on the immunohistochemistry. Lin's concordance correlation coefficient was used to measure the agreement between the MRI or ultrasound and tumor extent. Also, patients were classified into three groups according to the accuracy of MRI in correlation with tumor extent (concordance, underestimation, and overestimation). Tumor extent was defined as pathologic tumor size including in situ carcinoma.
Results: In a total of 589 patients, 397(67.4%) women received BCS. Means of tumor size were 1.99 ± 0.91 cm by pathologic review, 1.91 ± 1.01 cm by MRI, and 1.76 ± 0.92 cm by ultrasonography, respectively. Correlation analysis revealed a similar concordance rate between MRI and ultrasound to pathologic tumor size (r= 0.622 and 0.573). Lin's concordance analysis showed that MRI showed more significant correlation with pathologic tumor size than ultrasound in patients with TNBC (r= 0.735 VS 0.593, p=0.0052). However, the proportion of concordant group did not differ significantly according to subtypes (p=0.279).
Conclusions: Our findings suggest that preoperative MRI does not increase the accuracy in predicting tumor extent or reduce the margin-positive rates in breast cancer.
Citation Format: Yang BS, Lee HW, Park JT, Lee HM, Ahn SG, Jeong J. Value of magnetic resonance imaging in preoperative predicting tumor extent in each subtypes of 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 P4-02-11.
Abstract P4-07-04: PARP1/2 inhibition in a subset of triple negative breast cancer (TNBC) patient-derived tumor xenografts (PDX) identifies predictive biomarkers of response
Authors: Serra V , Cruz C , Bruna A , Ibrahim YH , Vivancos A , Vivancos A , Nuciforo P , Bellet M , Gómez P , Pérez JM , Saura C , Vidal M , Serres X , Rueda OM , Peg V , Caldas C , O'Connor MJ , Baselga J , Cortés J 
Published: May 2016

Abstract
Background: BRCA1/2 mutation carriers (gBRCA) have a higher risk of breast or ovarian cancer, since BRCA1/2 mutation results in impaired high-fidelity DNA repair by homologous recombination (HR) and subsequently genetic instability. In non-gBRCA TNBC, HR deficiency occurs at the somatic level, by means of BRCA1 mutation, BRCA1 epigenetic loss or mutation in other HR-associated genes. Because PARP1/2 inhibitors (PARPi) are well-tolerated and active anti-cancer agents in the advanced setting of gBRCA tumors, we sought to expand their applicability by identifying response biomarkers in TNBC.
Methods: We have assessed the antitumor response of the PARP1/2 inhibitor olaparib as single agent in a panel of 12 primary and advanced TNBC PDX models. On PDXs exhibiting primary sensitivity to olaparib, we have developed models of acquired resistance by continuous exposure to the drug and identifying progression on treatment. We have characterized the models through targeted sequencing and the analysis of the hypermethylation and expression levels of BRCA1 transcript to find potential correlates of drug-sensitivity.
Results: Three out of 12 PDXs (25%) treated with single agent olaparib, exhibit tumor regression or disease stabilization. BRCA1 is hypermethylated in two of these PARPi-sensitive TNBC PDX models and is associated with loss of BRCA1 mRNA expression. The third PARPi-sensitive TNBC PDX harbors a frameshift, heterozygous PALB2 mutation, which is no longer detected in the acquired resistance PDX model. Acquired resistance in the hypermethylated PDXs is under study as well as the duration of response compared to gBRCA PDX models.
Conclusions: Our study highlights that somatic HR-deficiency is frequent in TNBC and provides the basis of sensitivity to PARPi.
Citation Format: Serra V, Cruz C, Bruna A, Ibrahim YH, Vivancos A, Vivancos A, Nuciforo P, Bellet M, Gómez P, Pérez JM, Saura C, Vidal M, Serres X, Rueda OM, Peg V, Caldas C, O'Connor MJ, Baselga J, Cortés J. PARP1/2 inhibition in a subset of triple negative breast cancer (TNBC) patient-derived tumor xenografts (PDX) identifies predictive biomarkers of response. [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 P4-07-04.
Abstract P4-09-21: Dual expression of aquaporin 3 and 5 in patients with early breast cancer
Authors: Lee SJ , Chae YS , Kwon TJ , Chung JH , Lee J , Jung JH , Kim WW , Park HY , Jeong JY , Park S-H , Park S 
Published: May 2016

Abstract
Background: We reported separately that AQP5 or AQP3 expression in tumor tissue may predict survival after surgery for the specific types of early breast cancer (EBC). However, there is no definitive evidence for the role of dual expression of the two AQPs. Therefore, the current study focused the association and its prognostic impact of their tumoral expressions in the same patients.
Patients and Methods: AQP3 and AQP5 expressions were investigated on the basis of the immunohistochemistry of tissue microarray specimens from 447 EBC patients who underwent surgery between 2003 and 2008 as described in previous studies. Patients were divided into 4 subgroups based on AQP3 and AQP5 expressions: group1 for (-/-), group2 for (-/+), group 3 for (+/-), and group 4 for (+/+), respectively.
Results: Among 477 patients, the number of patients for each group was as follows: group 1 (n=193, 43.2%), group 2 (n=74, 16.6%), group3 (n=110, 24.6%) and group 4 (n=70, 15.7%), respectively. In the current study a positive correlation was identified between AQP3 and 5 expressions (P=0.017 by a χ2- test) in particular for HER2- overexpressing and ER-positive tumors (P=0.009 and 0.044, respectively). Multivariate survival analysis showed that dual expression of AQP3 and AQP5 was a negative prognostic factor for relapse-free or distant disease-free survival for patients with HER2-overexpressing EBC (HR=3.107 and 3.683; P=0.043 and 0.027, respectively), statistically more prominent compared in case with AQP3 expression alone (HR=3.137 and 2.784; P=0.036 and 0.070, respectively).
Conclusion: Dual expression of AQP3 and AQP5 in tumor tissue may be considered as a potential prognostic marker in patients with HER2-overexpressing EBC after curative surgery.
Citation Format: Lee SJ, Chae YS, Kwon TJ, Chung JH, Lee J, Jung JH, Kim WW, Park HY, Jeong JY, Park S-H, Park S. Dual expression of aquaporin 3 and 5 in patients with early 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 P4-09-21.
Abstract P5-01-06: 18F-radiolabeled PARP-1 inhibitor uptake as a marker of PARP-1 activity in breast cancer
Authors: Edmonds CE , Lieberman BP , Xu K , Zeng C , Makvandi M , Li S , Hou C , Lee H , Greenberg RA , Mankoff DA , Mach RH 
Published: May 2016

Abstract
Objectives: The nuclear enzyme PARP-1 plays a central role in sensing DNA damage and facilitating repair. Tumors with BRCA1/2 mutations are highly dependent on PARP-1 as an alternative mechanism for DNA repair, and PARP inhibitors generate synthetic lethality in tumors with BRCA mutations, resulting in cell cycle arrest and apoptosis. Zhou et al. recently synthesized an 18F-labeled PARP-1 inhibitor (18F-FluorThanatrace) for PET, and demonstrated high specific tracer uptake in a xenograft model of breast cancer (Zhou, Bioorg Med Chem, 22:1700, 2014). The current study seeks to quantify the relationship between 18F-FluorThanatrace binding (both in vitro and on PET imaging of human tumor xenografts) and the level of constitutively active PARP-1, using multiple human breast cancer cell lines, including a BRCA1 defective line.
Methods: BRCA1 defective HCC1937, triple negative MDA-MB-231, and luminal A MCF-7 human breast cancer lines were assessed for constitutive PARP-1 activity via a chemiluminescent ELISA assay for PAR and by Western blot. The same cell lines were incubated with 18F-FluorThanatrace over various time increments, and tracer uptake was assayed via a gamma counter. Specificity of tracer binding was verified via co-incubation with competitive inhibitor Olaparib, and specific tracer uptake was calculated as the difference between uptake with and without Olaparib. Specific tracer uptake was compared to levels of constitutive PARP-1 activity in all cell lines. In addition, HCC1937 and MDA-MB-231 xenograft tumor models were imaged via 18F-FluorThanatrace-PET/CT, and PET uptake was correlated with PARP-1 activity.
Results: BRCA1-defective HCC1937 had higher constitutive PARP-1 activity than cell lines with intact BRCA1. In vitro levels of 18F-FluorThanatrace uptake correlated with constitutive PARP-1 activity across cell lines. In addition, 18F-FluorThanatrace measured by PET in xenograft breast cancer tumor models correlated with constitutive PARP-1 activity.
Conclusions: Tumor uptake of 18F-FluorThanatrace, both in vitro and on PET imaging of xenograft tumor models, quantitatively reflects differences in PARP-1 activity across different breast cancer cell lines, including BRCA1 defective. This motivates further studies of 18F-FluorThanatrace as an in vivo measure of PARP-1 activity and possibly as a predictive marker for PARP-1 therapy in patients, including those with BRCA1/2 mutations.
Citation Format: Edmonds CE, Lieberman BP, Xu K, Zeng C, Makvandi M, Li S, Hou C, Lee H, Greenberg RA, Mankoff DA, Mach RH. 18F-radiolabeled PARP-1 inhibitor uptake as a marker of PARP-1 activity 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 P5-01-06.
Abstract P5-02-01: Diagnosis of pathological complete response by vacuum-assisted minimal invasive biopsy after neoadjuvant chemotherapy in breast cancer - Results from a prospective pilot study
Authors: Hennigs A , Heil J 
Published: May 2016

Abstract
Purpose:
To explore the ability of vacuum-assisted-biopsy (VAB) to diagnose pathological complete response (pCR) or residual tumor in breast cancer patients after neoadjuvant chemotherapy (NACT).
Patients and methods: 50 patients (22 with clinical / imaging complete response 28 with clinical / imaging residual tumor) were included in this review-board approved prospective pilot study between 08/14 and 02/15. Vacuum-assisted-biopsy (VAB) was performed after NACT and before surgery. Negative predictive values (NPV) and false-negative-rates (FNR) to predict a pCR in surgical specimen (=diagnose pCR through VAB) were the main outcome measures.
Results:
The cohort (n=50) consisted of 15 (30%) triple negative (TNBC), 13 (26%) HER2 positive (HER2+) and 22 (44%) hormone receptor positive / HER2 negative (HR+/HER2-) cancers. pCR in surgical specimen was diagnosed in 23 (46%) cases of the whole cohort. The NPV of the VAB diagnosis of pCR was 94.4% (95% CI: [0.84; 1.00]). The FNR was 3.7% (95% CI: [0; 0.12]) and specificity 73.9% (95% CI: [0.54; 0.94]). Taking only those biopsies into account that pathology confirmed to be representative of the (former) tumor region, improved the outcome of VAB to a specificity of 100% while the NPV (94.4% (95% CI: [0.84; 1.00]) and the FNR (4.8% (95% CI: [0.00; 0.15]) stayed the same.
Conclusion:
Overall accuracy of VAB diagnosis of pCR questions the necessity of surgical intervention to diagnose a pCR. A confirmative, multi-center, intra-individually-controlled clinical trial including patients with clinical complete, near complete or partial response to NACT to validate the above mentioned results is warranted.
Citation Format: Hennigs A, Heil J. Diagnosis of pathological complete response by vacuum-assisted minimal invasive biopsy after neoadjuvant chemotherapy in breast cancer - Results from a prospective pilot study. [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 P5-02-01.