bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III study of receptor-targeted 99mTc-tilmanocept versus blue dye in the evaluation of SLNs in breast cancer and melanoma.
Authors: Cope F. O. , Sondak V. K. , Wallace A. M. 
Published: February 2017

LBA8526^ Background: Intraoperative lymphatic mapping (ILM) evaluation is widely used for staging clinically node-negative breast CA and melanoma. [99mTc]Tilmanocept (TcT) is a novel CD206 receptor-targeted (intra-nodal CD206+ RE cells) radiopharmaceutical designed for ILM of nodes (LNs) with anatomic nexuses to the tumor bed. We report the results of a Phase III, multicenter trial designed to assess the ILM performance of TcT vs the approved standard, vital blue dye (VBD) in both melanoma and breast CA patients (pts). Methods: 8 centers provided 153 pts w/ 10 melanoma or breast CA (ECOG 0-2; T1-4, N0, M0). TcT (50 µg @ 0.5-1.0mC i 99mTc) and VBD (per label) were injected to each pt; ILM was performed w/ a hand held γ-detector (for TcT) and visual eval (for VBD); all γ+ and blue+ LNs were excised and histologically examined. TcT was injected per study center practice (subareolar and intradermal injection w/ >0.5 hr wait); VBD was injected at surgery. The 10 endpoints were concordance w/ TcT and VBD (% of LNs detected by VBD and identified by TcT) and reverse concordance (% LNs detected by TcT and identified by VBD); path +/- per localization of TcT and VBD were also assessed. Pts were assessed for lab safety and AEs. Results: (Table) VBD pts (standard ILM pt metric) who expressed ≥1 VBD+ LN equate to the intent-to-treat (ITT) group. Conversely, the reverse ITT (RITT) group consisted of pts expressing ≥1 γ+ node. The analyses of the 10 endpoints are estimates of the 95% CIs. The 10 hypothesis is H0: R ≤0.90 vs Ha: R >0.90; R = concordance rate (2-sided, α = 0.05). Additional contrasts include tests for Δ residual disease (path) and effect on pt staging. Conclusions: The receptor targeted ILM agent, TcT, provided clinically superior results compared to label-approved VBD. TcT localization of occult disease was significantly improved vs VBD. The results suggest that receptor targeting of the lymphatic RE cells is a key development in ILM of LN metastasis. [Table: see text]
Association between bisphosphonate use in metastatic breast cancer (MBC) and overall survival.
Authors: Mathew A. , Rosenzweig M. Q. , Brufsky A. 
Published: February 2017

102 Background: Preclinical studies on bisphosphonates in breast cancer have suggested an anti-tumor effect in addition to its bone protective role. However, randomized controlled trials of bisphosphonates versus placebo have found little evidence of increased overall survival (OS) in MBC. We conducted a retrospective single-institution cohort study of MBC patients to evaluate the association between bisphosphonate use and overall survival. Methods: Baseline demographic and tumor specific data were collected on newly diagnosed MBC patients between January 1998 and December 2009. Other variables included the number and sites of each metastasis, use of baseline neoadjuvant and adjuvant chemotherapy, and use of hormone therapy. Bisphosphonate use was defined as present if it was administered for a period of at least 3 months in the metastatic setting. Overall survival was determined from the date of diagnosis of first metastatic disease. Survival analysis was performed using the Kaplan-Meier method and Cox proportional-hazards model. Results: Data were available on 737 patients with MBC, of whom 434 died during a median follow-up of 2 years; median age was 50.3 years. 92% of patients were Caucasian; 32% were both ER and PR-negative; and 31% were HER2-positive. Over 67% of MBC patients had bone metastasis and nearly 80% received bisphosphonates. Multivariate analysis found an overall survival benefit for bisphosphonate use, with a hazard ratio of 0.63 (95% confidence interval: 0.48-0.84; p<0.002), when adjusted for variables with significant effect on survival on univariate analysis and other known prognostic variables. These variables include age, stage at diagnosis, race, hormone receptor status, HER2 status, and number of metastatic sites, presence of bone metastasis and the use of adjuvant therapy. The administration of adjuvant therapy did not yield a significant survival advantage in the analyses. Conclusions: This retrospective cohort study provides evidence for an OS benefit with the use of bisphosphonates in MBC even after controlling for other significant prognostic factors.
Statin treatment use in diabetic patients with breast cancer: A potential C-reactive protein mediated benefit.
Authors: Ceacareanu A. C. , Hong C. , Brennan J. J. , Epstein M. , Kossoff E. , Nimako G. K. , Patel K. , Forrest A. 
Published: February 2017

173 Background: Statin treatment has not yet been evaluated in relation to breast cancer (BC) prognosis in diabetes mellitus (DM) patients. Reported decreased survival following BC in women with metabolic syndrome, led us to investigate whether specific statin therapy may lead to improved BC survival. Reported associations between elevated C-reactive protein (CRP) levels at the time of diagnosis with worse cancer prognosis, and CRP-lowering properties of statin treatment in non-cancer patients, led us to investigate whether statin use is associated with lower CRP levels at the time of BC diagnosis and with improved BC outcomes. Methods: All DM patients newly diagnosed with BC between 2003 and 2007 (Roswell Park Cancer Institute) were retrospectively reviewed (n = 225). BC pathology, outcomes, existing comorbidities and drug therapy were documented. Follow up began at BC diagnosis and ended with first confirmed recurrence and/or death, or last date of follow-up. Hazard ratios (HR) and 95% confidence intervals (CI)s representing the association between statins, BC and a defined event were computed with Cox proportional hazards model. CRP plasma levels were determined by enzyme-linked immunosorbent assay in specimens donated at the time of BC diagnosis. A total of 98 study patients, DM+BC, and their matched controls, BC only (n = 196) were analyzed. Results: After a median follow up of 30 months, patients receiving statins for cholesterol management were found to have better disease-free survival (HR 0.27, 95% CI: 0.10, 0.71, X2 = 7.31, p = 0.06), and lower overall mortality (HR 0.23, 95% CI: 0.08, 0.66, X2 = 7.80, p = 0.05) compared to patients not receiving any cholesterol management medication. CRP levels have ranged between 0.2 and 21 mg/L and clinically relevant levels ( > 3mg/L) were noted in the study group. Conclusions: This study explored for the first time the association between statin therapy and BC prognosis in DM. We observed improved outcomes in statin-treated patients. While we currently analyze statin therapy in relationship with baseline CRP levels and BC prognosis, our existing findings suggest that statins have the potential to improve BC outcomes potentially through lowering overall inflammation.
Demography and treatment outcomes of triple-negative breast cancer: A single institution study.
Authors: James S. E. , Vos P. , Biswas T. 
Published: February 2017

179 Background: Triple negative breast cancer (TNBC) constitutes about 11-20% of all cases of breast cancer. TNBC has particularly aggressive clinical course and worse prognosis especially in African American (AA) women compared to white women. This retrospective study aims to investigate TNBC in the eastern North Carolina (NC) population, report treatment outcomes and determine the rate of recurrence. Methods: 202 TNBC patients treated at our institution between 1/01 and 11/09 were included in this analysis. Eastern NC has an AA population higher than the national average (30.2% vs. 12.4%) which is reflected in our patient demographics with 111 (55%) AA, 84 (41.6%) White, 5 (2.5%) Hispanic and 2 (1%) Chinese patients. Stage distribution was 41 (20%) stage I, 97 (48%) stage II, 37 (18%) stage III, 16 (8%) stage IV disease. Six patients (3%) had a diagnosis of DCIS and 5 (3%) were unknown. Majority was (79%) poorly differentiated carcinoma followed by moderately differentiated (13%) carcinoma. Variables were compared between groups using two-sample t-tests. Kaplan Meier curves were generated for overall survival (OS). Group was compared by log rank test. Results: The median FU time was 4.73 years (1.2–10.2). Median age at diagnosis was 53 (22-88) years overall, 51 years for AA and 57 years for White (p=0.01) patients. The overall median survival was 32.18 months with no difference between AA (32.39 months) and white (29.7 months) patients (p=0.785). 160 patients with stage I-III disease received chemotherapy with 96 patients (60%) receiving adjuvant and 64 (40%) receiving neoadjuvant therapy. The median survival for adjuvant patients was 37.08 months (6.87–113) vs 26.48 months (1.51–87.49) for neoadjuvant patients (p=0.001). 27 (14%) patients with stage I-III diseases experienced a local recurrence, 31 patients (15%) experienced distal recurrence with a median time to failure of 25.6 months. Conclusions: This study demonstrated no significant difference in median survival between AA and white patients; however, AA women were diagnosed at a younger age compared to white women. Patients treated with adjuvant chemotherapy had a significantly greater median survival when compared to patients receiving neoadjuvant treatment.
Reasons for choosing contralateral prophylactic mastectomies in women who test negative for the BRCA mutation: A retrospective questionnaire.
Authors: Howard-McNatt M. M. , Hurt G. , Levine E. A. ,   Society Surgical Oncology
Published: February 2017

192 Background: Determination of BRCA1and 2 mutation carrier’s status has become increasingly important. BRCA1/2 carriers are offered bilateral mastectomy (BLM) and prophylactic oophorectomy. Those who test negative typically do not undergo such extensive surgery. However, there is a cohort of women who still decide to have BLM at the time of their breast cancer diagnosis despite testing negative for the mutation. A questionnaire was sent to women who had prophylactic mastectomies to determine the reasons for their surgical choice. Methods: Women who received BRCA1 and 2 testing and tested negative but chose bilateral mastectomies between January 2005- May, 2010 were sent a questionnaire. For those who expressed an opinion, a two-sided Fisher exact test was used to compare responses. Patient demographics, family history, reasons for choosing mastectomy, and satisfaction were recorded. Results: A total of 35 surveys were mailed, and 28 were returned (80%). The mean patient age at diagnosis was 41.9 years. The majority of women were Caucasian, had some college to postgraduate education, and had children. 64% had a relative with breast cancer. Fear was the main reason why these women choose BLM. The majority had breast reconstruction and overall 71% were very satisfied with their surgical choice. Conclusions: Increased rates of contralateral prophylactic mastectomies have been observed in women with negative BRCA results. In our study Caucasian, educated, married women were more likely to choose BLM. The main reason women gave for choosing BLM was fear of recurrence. Prospective studies are needed to examine factors effecting patient decision-making.
What factors affect the place of end-of-life care for patients with metastatic breast cancer?
Authors: Harano K. , Yonemori K. , Hashimoto K. , Yunokawa M. , Shimizu C. , Tamura K. , Katsumata N. , Ando M. , Fujiwara Y. 
Published: February 2017

218 Background: Despite the early detection and treatment, advanced breast cancer is still impossible to cure. Palliative care has become the standard of care at the time of end-of-life (EOL). However, there are limited data about the degree of access to such care and the factors that affect the choice of place to die. The purpose of this study is to identify factors that affect the place of EOL care in patients with metastatic breast cancer in Japan. Methods: Our study included breast cancer patients who were diagnosed with recurrence or metastatic diseases between 2004 and 2010 at the National Cancer Center Hospital and received EOL care. The following data were obtained: treatments, place of EOL care, and social background such as age, whether patients had young children, whether patients had elderly family members who needed nursing care, whether patients had jobs at the time of recurrence, and where they lived in. Results: Overall, 124 patients met our inclusion criteria. Among them, only 13% of patients received EOL care at home and 43.5% of patients at hospices, while 43.5% of patients died in acute care beds. Patients who had jobs at the time of recurrence were significantly more likely to receive EOL care in acute care beds (odds ratio 2.46; 95% CI 1.04−5.83). Other social backgrounds were not significantly related to the place of EOL care. Conclusions: A sizable proportion of patients, especially patients who had jobs at the time of recurrence, received acute care at the EOL and did not have access to palliative care at home or hospices. Familial backgrounds were not the determinant to choose the place of EOL.
Purinergic mechanisms in breast cancer metastasis.
Authors: Buxton I. L. 
Published: February 2017

229 Background: Breast cancers survive in patients in a dormant state only to grow as metastatic disease in the future. Surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Many breast cancer deaths might be averted if we understand the cellular mechanisms underlying escape from dormancy. We have proposed that extracellular nucleotide signaling constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. We demonstrate a role for the dinucleotide kinase NM23/NDPK in the generation of signals that stimulate angiogenesis and escape from latency. Methods: We have employed protein purification and identification by Western blot, tubulogenesis, migration and proliferation assays in human endothelial cells, signaling assays of receptor activation, nucleotide and receptor transactivation/phosphorylation assays and tumor growth and metastasis imaging in immunocompromized mice (SCID) to establish a role of r nucleotides in breast cancer metastasis. Results: A panel of breast cancer cell lines, but not normal breast cells, shed/secrete large amounts of NM23 that is active as an ADP transphosphorylase. NM23 stimulates tubulogenesis, proliferation and migration in cultures of human endothelial cells in a manner blocked by purinergic receptor antagonist, inhibitors of the nucleoside diphosphate kinase activity of NM23, or by VEGFR2 antagonists. In SCID mice carrying MDA-MB-231 luciferase over-expressing breast cancers, NM23 appears in the blood early in tumorigenesis. Treatment with the P2Y1 receptor antagonist MRS2179, or the NM23 antagonist ellagic acid slows the growth of primary breast tumors and prevents metastatic tumor formation. Conclusions: NM23 secretion leading to nucleotide generation activates endothelial P2Y1 receptors resulting in transactivation of VEGFR2 and angiogenesis in support of metastasis. Identification of Nm23 as a marker of early of breast cancer development and blockade of the extracellular actions of NM23 offer a new approach to breast cancer detection and treatment.
Reproductive health algorithm.
Authors: Patel A. , Radeke E. K. , Uy A. , Zaren H. A. 
Published: February 2017

263 Background: About 692,000 women are newly diagnosed with various cancers yearly in the US, with breast being the most common, and 10% within reproductive age group. When concerned about survival, reproductive health is overlooked. The objective of this study was to incorporate a reproductive health algorithm into oncologic care of reproductive aged women. Methods: This prospective observational study was conducted at John H. Stroger, Jr. Hospital of Cook County. Eleven newly diagnosed patients were recruited. The algorithm was implemented for each participant and they were surveyed quarterly for 2 years. Results: The mean age of participants was 39 and mean living children was 1.9. Of the 11 women, two (18%) were pregnant at the time of recruitment and nine were not. Both pregnant subjects had an obstetric consultation and chose to continue the pregnancies. They delivered without complications. One began chemotherapy in the second trimester, the other began postpartum. After completion of the pregnancies, these women went into the “not pregnant” cohort. Of the now 11 women in the “not pregnant” cohort, one (9%) had not completed childbearing and 10 (91%) had. The one woman interested in childbearing underwent REI consultation and fertility preservation counseling. Of the women who had completed childbearing, 70% had adopted a long term contraceptive method, 10% a short term method and 20% were abstinent. All 11 women had a family planning consultation. Eighteen percent had already undergone permanent sterilization and 27% had an IUD in place at the time of diagnosis. An additional 27% selected an IUD. Seventy-two percent continued or began long term contraception. Eighteen percent remained abstinent throughout study period. Conclusions: Conclusions from this study demonstrate that with the intervention of the algorithm and referral system, 100% of patients had a basic management plan consistent with reproductive health goals. Most selected a form of long term contraception prior to or on study. All sexually active women had a contraceptive plan in place post diagnosis and during treatment of cancer consistent with long term reproductive health goals. A cluster-design, multicenter, randomized controlled trial has been developed to further investigate and validate our findings.
A multicenter, open-label phase II trial of dovitinib, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, in FGFR1-amplified and nonamplified metastatic breast cancer (BC).
Authors: Andre F. , Bachelot T. D. , Campone M. , Dalenc F. , Perez-Garcia J. M. , Hurvitz S. A. , Turner N. C. , Rugo H. S. , Baselga J. , Zhang Y. ,   Novartis Oncology Clinical Group
Published: February 2017

289 Background: Amplification of the FGFR1 gene occurs in ≈ 10% of BC, correlates with FGFR1 overexpression, and is mainly observed in estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)- BCs. Dovitinib (TKI258) is a multitargeted tyrosine kinase inhibitor that demonstrated potent antitumor activities in FGFR1-amplified tumor cell lines. This phase 2 study evaluated the efficacy and safety of dovitinib in metastatic HER2- BC. Methods: Patients were stratified into 4 groups based on FGFR1 and hormone receptor (HR) tumor subtype: 1) FGFR1+, HR+; 2) FGFR1+, HR-; 3) FGFR1-, HR+; 4) FGFR1-, HR-. Screening for FGFR1 status was performed by fluorescence/chromogenic in situ hybridization (cutoff ≥ 6 gene copies). Dovitinib (500 mg) was administered once daily on a 5-day-on/ 2-day-off schedule. The primary endpoint was RECIST best overall response rate in patients with measurable disease per external radiology review. Results: Data from 77 of 81 treated patients were available as of January 2011 (n=21, n=34, n=22 in groups 1, 3, 4, respectively). Median number of prior therapies in the metastatic setting was 2 chemotherapy lines (all patients) and 2 endocrine therapy lines (HR+ patients). Liver metastases were present in 58% of patients (81%, 50%, 50% in groups 1, 3, 4, respectively). Most common adverse events included vomiting (75%; grade 3 [g3]: 6%), diarrhea (72%; g3: 6%), nausea (62%; g3: 5%), and asthenia (61%; g3: 17%). Median dovitinib exposure was 1.7 (range, 0-8.2) months, including 8 patients with > 4 months of therapy. Of patients with measurable disease at baseline, in group 1, 13% had unconfirmed partial responses and 44% had stable disease ≥ 4 months (SD4). In groups 3 and 4, 29% and 11% had SD4. Conclusions: This is the first trial reporting efficacy of an FGFR1 inhibitor in patients with FGFR1-amplified BC. Dovitinib showed antitumor activity in patients with HR+, FGFR1- amplified BC and disease stabilization in other subgroups. FGFR1 is likely a relevant target in BC, and FGFR1 amplification may define a segment of dovitinib-sensitive disease. Further evaluation of dovitinib in patients with HR+ BC is planned.
The effects of substance P fragments on breast cancer cells.
Authors: Oz E. , Aydemir E. , Korcum A. F. , Fiskin K. 
Published: February 2017

295 Background: Substance P (SP), a neuropeptide, is known to induce tumor cell proliferation. In contrast with intact peptide, the fragments of SP are suggested to inhibit the growth of various cancer cells. The aim of the present study was to determine cytotoxic effects of physiological fragments of SP either alone or in combination with radiotherapy on mouse breast cancer cells. Methods: In this study, we tested the physiological fragments of SP such as SP (4-11), SP (6-11) and SP (1-7). Dose-response and time-course studies were carried out with various concentrations (100-0.001 nM) of SP fragments and the intact peptide. 4T1 mouse breast cancer cell lines were used in this study. The cytotoxic effect of SP fragments alone or in combination with radiotherapy was determined via WST-1 assay. Changes in substance P amounts in cells and in mediums determined by SP EIA kit. Results: SP(4-11) and SP(6-11), but not SP(1-7), inhibited the proliferation of breast cancer cells and potentiated antitumor effects of radiotherapy. Moreover, the intact peptide alone did not alter the proliferation rate of 4T1 cells and the cytotoxic effects of the fragments were not inhibited by SP. Conclusions: These results demonstrate that combined treatment with 2 fragments of SP (4-11 and 6-11) and radiotherapy induce cytotoxic effects. These data may provide the basis for a strategy, in which it is possible to use SP fragments and radiotherapy together to improve the efficiency of the independent therapies.