bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-11-04: Serum IgG response against prostate-related antigen revealed by personalized peptide vaccination in patients with metastatic recurrent breast cancer
Authors: Toh U , Okabe M , Iwakuma N , Mishima M , Shichijo S , Yamada A , Noguchi M , Itoh K , Akagi Y 
Published: May 2016

Abstract
Purpose: We have indicated that IgG and CTL boosting response could be a potential prognostic factor for overall survival (OS) and progression free survival (PFS) in metastatic recurrent breast cancer (mrBC) patients, who had received personalized selected peptide vaccine (PPV) therapy in our previously reported clinical phase II study. The aim of this study is to identify the prognostic role of serum value of IgG antibody against prostate related-antigen (PRA), including prostate-specific antigen (PSA), prostate specific membrane antigen (PSMA) and prostate acid phosphatase (PAP) in mrBC patients
Methods: Peripheral blood samples of 77 patients with mrBC were analyzed for serum anti-PRA IgG levels before and after 6th and 12th PPV therapy prospectively. Most of the peptides using for PPV are derived from cancer associated antigens expressing in various types of advanced cancers, but the peptides derived from PRAs were not used in this study.
Results: After PPV therapy, total serum levels of anti-PRA IgG were significantly increased in 31 mrBC patients (Group 1) whereas in remaining 46 rmBC patients (Group 2). Either serum anti-PSA, anti-PAP and/or anti-PMSA IgGs showed a significant increase in patients of Group 1 after 6th (p=0.045) and 12th PPV treatment (p &lt; 0.001), irrespective of their intrinsic subtypes. The median PFS and median OS of Group 1 patients were 8.1 and 14.3 months, while those of Group 2 patients were 5.1 and 10.8 months, respectively. Anti-PRA IgG levels were significantly associated with PFS (p=0.0073; HR: 0.37) and OS (p=0.025; HR: 0.43) between these two groups, whereas no significant relation was found with age, clinical response rate and recurrent metastatic status.
Conclusions: The Group 1 patients with elevated anti-PRA IgG may have better prognosis compared to Group 2 patients who showed no IgG elevation after PPV treatment for rmBC. These results indicated a clinical significance between pre-and post- treatment measurement of serum anti-PRA IgGs in mrBC patients receiving PPV therapy, and may be a useful prognostic marker for monitoring the outcome to PPV treatment of breast cancer.
Citation Format: Toh U, Okabe M, Iwakuma N, Mishima M, Shichijo S, Yamada A, Noguchi M, Itoh K, Akagi Y. Serum IgG response against prostate-related antigen revealed by personalized peptide vaccination in patients with metastatic recurrent 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 P2-11-04.
Abstract P2-13-08: Breast lipofilling: A systematic review of current practice and oncological safety
Authors: Wazir U , Kasem A , Headon H , Mokbel K 
Published: May 2016

Abstract
Background: Lipofilling is a reconstructive and aesthetic technique that has recently grown in popularity and is increasingly being used in breast surgery. Concerns had been raised regarding its safety when used for remodelling and reconstruction of the breast.
Methods: We reviewed the current literature by systematically searching PubMed and Google Scholar databases regarding the current evidence regarding the oncological safety of the procedure in patients seeking aesthetic breast enhancement and in patients requiring oncoplastic reconstruction.
Results: Among the 864 patients included in the currently available studies on breast cancer patients who underwent lipofilling, only 14 (1.6%) recurrences were identified. However, evidence has emerged suggestive that the use of lipofilling in the background of ductal carcinoma in situ (DCIS) may be associated with an increased risk of neoplasia.
Conclusions: Over the subsequent two decades, little evidence has been found to support these early theoretical concerns, and growing numbers of proponents of the procedure are confident in its safety. Further study is required to better delineate the effect of lipofilling on DCIS.
Citation Format: Wazir U, Kasem A, Headon H, Mokbel K. Breast lipofilling: A systematic review of current practice and oncological safety. [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 P2-13-08.
Abstract P3-05-07: RAD1901, a novel oral, selective estrogen receptor degrader (SERD) with single agent efficacy in an ER+ primary patent derived ESR1 mutant xenograft model
Authors: Garner F , Brown J , Katzenellenbogen J , Lyttle CR , Hattersley G 
Published: May 2016

Abstract
Despite advances in the treatment of metastatic breast cancer, many women eventually relapse with more aggressive forms of endocrine-resistant disease. Mutations in the ESR1 gene encoding the estrogen receptor (ER) have recently emerged as a potential mechanism for the development of clinical resistance to conventional anti-estrogen therapies, such as fulvestrant. To overcome some of the pharmacokinetic limitations and intramuscular administration challenges associated with fulvestrant endocrine therapy and to combat the development of resistance, there is a significant need for the development of more durable and more effective ER-targeted therapies. Here, we begin to describe and characterize the preclinical efficacy of RAD1901, a novel, orally bioavailable small-molecule SERD, with significant therapeutic potential for treatment of breast cancer. RAD1901 selectively binds to and degrades the ER and is a potent antagonist of ER-positive breast cancer cell proliferation. Importantly, RAD1901 demonstrated profound tumor growth inhibition in MCF-7 xenograft models when compared to fulvestrant and tamoxifen. Importantly, RAD1901 also demonstrated marked single agent efficacy in a primary patient-derived xenograft (PDx) model harboring the ESR1 Y537S mutation indicating the utility of this SERD against clinically relevant ER mutants. Further biochemical binding studies and co-crystallization experiments of RAD1901 bound to the ER further confirms the ability of RAD1901 to bind to both mutant and wild type forms of the ER. RAD1901 is currently undergoing clinical testing in postmenopausal women with ER-positive advanced breast cancer.
Citation Format: Garner F, Brown J, Katzenellenbogen J, Lyttle CR, Hattersley G. RAD1901, a novel oral, selective estrogen receptor degrader (SERD) with single agent efficacy in an ER+ primary patent derived ESR1 mutant xenograft model. [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 P3-05-07.
Abstract P3-05-12: Combination of anti-progranulin (GP88/PGRN) antibody and letrozole inhibits tumor formation of letrozole resistant breast cancer cell lines
Authors: Serrero G , Dong J , Yue B , Hicks D , Hayashi J 
Published: May 2016

Abstract
The 88 kDa glycoprotein GP88 (Progranulin, PCDGF, acrogranin) is the largest member of the granulin/epithelin family of growth modulators identified as a driver of tumorigenesis. GP88 (PGRN) was also shown to be overexpressed in invasive ductal carcinoma (IDC)whereas it was negative in benign tumors and normal mammry epithelial tissue, thereby establishing GP88 as a therapeutic and diagnostic target in breast cancer (BC). Our laboratory has developed validated tools to measure GP88 in tumor biopsies and biological fluids as well as blocking its action. WE showed that GP88 was secreted and detected in the serum of BC patients at an increased level when compared to healthy subjects. Pathological studies with 530 cases of ER+ IDC with clinical outcomes showed that GP88 tumor expression was an independent prognostic indicator of recurrence in early stage BC patients. Training study followed by an independent validation study demonstrated that high GP88 tissue expression (GP88 3+) was associated with a 4-fold increase in risk of recurrence at 5 years. A neutralizing anti-GP88 antibody AG1 was expressed in a high yield CHO cell line was developed. The present study examined the effect of AG1 in letrozole resistant cell line AGLetR developed by long term selection in letrozole supplemented medium. This cell line showed decreased letrozole responsiveness in vivo and therefore constituted an excellent model for investigating letrozole resistance in vitro as well as in vivo. Here we report the results of studies investigating the effect of various doses of AG1 on LetR tumor development in combination with letrozole for AGLetR. We show that treatment with AG1 (10 mg/kg i.p.) in combination with letrozole was efficient to maintain long term responsiveness and inhibit tumor growth. Letrozole alone (5mg/kg) was unable to inhibit tumor growth and showed a doubling of tumor volume. Interestingly, long term combination treatment lead to tumor regression and inhibited tumor growth.
These data suggest that inhibiting GP88 could provide a novel and alternative therapeutic strategy for patients with resistance to anti-estrogen therapy, being tamoxifen or letrozole.
This works is supported by 2R44CA124179, HHSN 261201200060C, and HHSN2612014400C from NCI.
Citation Format: Serrero G, Dong J, Yue B, Hicks D, Hayashi J. Combination of anti-progranulin (GP88/PGRN) antibody and letrozole inhibits tumor formation of letrozole resistant breast cancer cell lines. [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 P3-05-12.
Abstract P3-05-13: Estrogen-independent growth of ESR1-mutant breast cancer cells requires CDK4/6
Authors: Luo F , Le X , Jeselsohn R , Brown M , Garraway L 
Published: May 2016

Abstract
A recent breakthrough in cancer treatment has been the development of highly specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. CDK4/6 inhibitors, such as palbociclib, prevent cell cycle progression from growth phase (G1) to the DNA synthesis (S) phase of the cell cycle. Palbociclib, however, is only approved for first-line treatment of patients with estrogen receptor positive (ER+) breast cancer in combination with an aromatase inhibitor, letrozole. Approximately 20% of metastatic breast cancer patients, harbor an activating mutation in the ligand-binding domain (LBD) of the estrogen receptor gene, ESR1, which confers resistance to estrogen deprivation. It is unclear whether tumors harboring these endocrine treatment-associated mutations will also respond to CDK4/6 inhibition. We have found that estrogen-independent growth of ESR1 -mutant breast cancer cells requires CDK4/6. Thus, ESR1-mutant breast cancer cells are sensitive to CDK4/6 inhibition. Mechanistically, ERS1 LBD-mutant cells upregulate key mediators of the G1-S cell cycle transition. Furthermore, the sensitivity of ESR1-mutant breast cancer cells to CDK4/6 inhibition requires RB1. While cells expressing RB1 respond to CDK4/6 inhibition, knockout of RB1 via CRISPRs enables ESR1-mutant breast cancer cells to resist combined estrogen depletion and CDK4/6 inhibition. Our studies suggest that tumors harboring ESR1 LBD mutations and an intact RB1 will respond to combined CDK4/6 inhibition and estrogen deprivation.
Citation Format: Luo F, Le X, Jeselsohn R, Brown M, Garraway L. Estrogen-independent growth of ESR1-mutant breast cancer cells requires CDK4/6. [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 P3-05-13.
Abstract P3-11-04: Metabolic profiles in female Sprague-Dawley rats receiving either a standard (4% fat) or Western (20% fat) diet and changes in rats bearing mammary cancers
Authors: Thompson MD , Grubbs CJ , Moeinpour F , Steele VE , Miller MS , Lubet RA 
Published: May 2016

Abstract
The methylnitrosourea(MNU)-induced model of ER+ mammary cancers in female Sprague-Dawley rats has been routinely used in our laboratories for screening chemopreventive agents. We recently reported that metformin was ineffective in preventing mammary cancers in this model when given to rats on a standard diet (Thompson, et al, Cancer Prev Res. 2015;8:231-9). In this study, we evaluated metformin in rats placed on either standard diet (4% fat) or a Western diet (20% fat, low calcium). As fat calories, these diets were 8% and 42%, respectively. The rats were placed on standard diet or Western diet at 43 days of age, given MNU (via the jugular vein) once at 50 days of age, and administered metformin or vehicle at 57 days of age for the remainder of the study. Serum of the rats in the various groups was obtained at 78 days of age, and at the end of the study (when mammary tumors were present). The levels of approximately 500 metabolites were compared in the serum based on data obtained by Metabolon (Research Triangle Park, NC). These studies showed that each of the four groups [(standard diet (early and late) or Western diet (early and late)] yielded four clearly distinct patterns based on an unsupervised principal component analysis. Certain of the metabolites which were differentially expressed in serum from standard vs Western diets at the early time point were alpha-10-undecanoate, 13-methylmyristic acid, 4-hydroxy-benzoate, 2-amino-heptanpate, tocopherol, and nicotinamide. Certain of these were fatty acids and lipid soluble vitamins that one would expect to be altered. Comparing serum from standard vs Western diets at the late time point confirmed many of these metabolic differences. We also compared serum from the early and late time points since the latter serums were typically from animals with a significant number of mammary cancers. We observed a number of metabolite changes including 4-hydroxy-butyrate, acetyl-carnitine, oxalate, and threonate. These cancer- related profiles will be discussed at greater lengths. Altered profiles caused by the administration of metformin and other chemopreventive agents will also be discussed. Of interest, metformin was consistently ineffective in preventing mammary cancers in rats given either standard or Western diet. Supported by NCI contract HHSN261201200021I.
Citation Format: Thompson MD, Grubbs CJ, Moeinpour F, Steele VE, Miller MS, Lubet RA. Metabolic profiles in female Sprague-Dawley rats receiving either a standard (4% fat) or Western (20% fat) diet and changes in rats bearing mammary cancers. [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 P3-11-04.
Abstract P3-12-06: Active breathing control in the management of left-sided breast cancer with irradiation: A dosimetric analysis of cardiac and lung dose
Authors: Gogineni ES , Kehrer JD , Jones GC , Premo C , Stinson S 
Published: May 2016

Abstract
Purpose: Deep inspiratory breath hold (DIBH) is a technique that has been increasingly utilized over the past several years for the purpose of reducing the radiation dose received by the heart and ipsilateral lung during radiotherapy (RT) for breast cancer. The purpose of this study was to provide a comparative analysis of cardiac and lung dose in patients treated with and without moderate DIBH with an active breathing control (ABC) device during RT for left-sided breast cancer at a community radiation oncology center.
Methods: From June 2013 to December 2014, 83 patients with stages 0-III left-sided breast cancer were treated with RT. Of these, 45 patients underwent CT simulation with an ABC device and the remaining 38 patients underwent standard free-breathing CT simulation for RT planning. Twenty-eight patients in the ABC cohort were treated with standard tangent fields and 18 were treated with locoregional RT. The non-ABC cohort included 26 patients treated with standard tangents and 12 treated with locoregional RT. A 4- or 5-field technique was utilized in all locally advanced patients to allow for coverage of the supraclavicular fossa and internal mammary lymph nodes with inclusion of low axillary coverage based on individual risk factors. All patients were treated with 3D-conformal techniques utilizing multi-leaf collimators to block the heart. Comparisons were made between mean heart dose, heart V5, mean lung dose, and lung V5 with and without the use of ABC. Kruskal-Wallis tests were used to determine significance between groups with α for significance set at p ≤0.05.
Results: On combined analysis, the use of DIBH with ABC resulted in a reduction in heart V5 (1.5 versus 5.4%; p=0.018). Mean heart dose, mean lung dose, and lung V5 were not significantly improved with the use of ABC. On subgroup analysis, patients treated with locoregional RT had reduced mean heart dose (161 cGy versus 309 cGy; p=0.014) and heart V5 (2.3% versus 14.8%; p&lt;0.001) compared to patients treated with a standard free-breathing technique.
Conclusions: The use of ABC provided a significant reduction in heart V5 in all patients with left-sided breast cancer and in mean heart dose and heart V5 in patients treated with locoregional RT. This retrospective, single-institution analysis demonstrates the feasibility of implementing moderate DIBH with ABC technology in the treatment of left-sided breast cancer in a community radiation oncology center.
Citation Format: Gogineni ES, Kehrer JD, Jones GC, Premo C, Stinson S. Active breathing control in the management of left-sided breast cancer with irradiation: A dosimetric analysis of cardiac and lung dose. [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 P3-12-06.
Abstract P3-12-16: Hydrosorb® versus control (water based spray) in the management of radio-induced skin toxicity: Results of multicentre controlled randomized trial
Authors: Bazire L , Fromentin I , Diallo A , de Lalande B , Pernin V , Dendale R , Fourquet A , Savignoni A , Kirova Y 
Published: May 2016

Abstract
Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus control (water based spray) in the topical treatment of grade 1 and 2 radiation dermatitis in population of patients treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT).
Patients and Methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during normo fractionated postoperative radiotherapy were eligible (according to the CTCAE v3 scale). They were randomised to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of radiotherapy because of skin radiotoxicity or and/or change of local cares for skin alteration. Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Pain was assessed according to two classes with a VAS cut-off of 2.
Results: Two-hundred seventy eight patients were enrolled (A = 142, B = 136). There were 186 successfully treated patients (82 in Hydrosorb® arm, and 74 in the control arm). There were 60 "failures" in the Hydrosorb® arm, and 62 in the control arm (p = 0.72), but mostly without interruption of the radiotherapy. Twenty-four patients stopped the radiotherapy treatment for local cares (16 in Hydrosorb®, arm and 8 in control arm). No risk factors were associated with failure to local treatment. The average absolute reduction of colorimetric levels between day 28 and day 0 was 4 in the Hydrosorb®, and 4.2 in the water spray groups, respectively (p = 0.36). Forty-eight patients in the Hydrosorb® arm had a VAS &gt; 2 versus 51 patients in the placebo arm, i.e. 34% and 38%, respectively (p = 0.45). A significant reduction of pain was observed on D7 (p = 0.04) and D21 (p = 0.01) in the Hydrosorb® arm. Sixty patients in the Hydrosorb® arm and 55 patients in the placebo arm had moderately to severely altered quality of life (p = 0.76).
Conclusions: The present study showed no significant difference between Hydrosorb® and simple water spray in the treatment of acute radio-induced dermatitis even if there was a trend to an improvement in pain at the first weeks after the treatment. Systematic prevention measures and modern breast cancer radiotherapy techniques now allow excellent tolerability, but the place of topical treatment to optimize this tolerability has yet to be defined.
Citation Format: Bazire L, Fromentin I, Diallo A, de Lalande B, Pernin V, Dendale R, Fourquet A, Savignoni A, Kirova Y. Hydrosorb® versus control (water based spray) in the management of radio-induced skin toxicity: Results of multicentre controlled randomized trial. [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 P3-12-16.
Abstract P3-12-21: Post-mastectomy radiotherapy for T3N0 breast cancers: A retrospective, multi-institution review
Authors: Frandsen JE , Cannon G , Poppe M 
Published: May 2016

Abstract
Purpose
The role of post-mastectomy radiotherapy (PMRT) for node-negative breast cancers that are larger than five centimeters remains undefined. The purpose of this study was to report outcomes for women with T3N0 breast cancers treated with and without PMRT.
Methods
T3N0 breast cancers diagnosed between 1985 and 2014 were collected from the tumor registries of two large healthcare systems. For the purpose of our analysis, patients were divided into two groups: (1) women who received PMRT and (2) those who did not receive PMRT. Chi-square and students t-tests were used to compare baseline characteristics. Kaplan Meier estimates were used to analyze freedom from locoregional recurrence (FFLR), relapse free survival (RFS), and overall survival (OS).
Results
This analysis identified 93 women with T3N0 breast cancers. Of these, 53 received PMRT and 40 did not. Median follow up was 6.2 years and 5.3 years in the non-PMRT and PMRT cohorts, respectively. Women not undergoing PMRT were more likely to be diagnosed in the 1980s and 1990s than women receiving PMRT (p&lt; 0.05). Adjuvant chemotherapy and endocrine therapy were less frequently given in patients not receiving PMRT (p&lt;0.05), again associated with an earlier treatment era. There was a trend toward increased FFLR in the women receiving PMRT (p=0.15). FFLR in the PMRT cohort was 97.9% and 97.9% at five and ten years, respectively. For women not receiving PMRT, FFLR was 88.4% and 88.4% at five and ten years, respectively. RFS (p=0.66) and OS (p=0.48) were similar.
Conclusions
Women not receiving PMRT in our study had a locoregional failure rate of only 11.6% at ten years despite receiving inferior systemic treatment by current standards. Locoregional control after PMRT for T3N0 breast cancers was excellent with a 2.1% failure rate at ten years. Further research is needed to define PMRT indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines.
Citation Format: Frandsen JE, Cannon G, Poppe M. Post-mastectomy radiotherapy for T3N0 breast cancers: A retrospective, multi-institution review. [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 P3-12-21.