bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship of BTG2 expression and anastrozole resistance in breast cancer.
Authors: Nishiya S. , Jinno H. , Hayashida T. , Takahashi M. , Kitagawa Y. 
Published: February 2017

220 Background: The B-cell translocation gene-2 (BTG2) belongs to a class of proteins known as the Tob and BTG antiproliferative protein family. It was shown that estrogen and progesterone suppress BTG2 expression for the development of mammary gland. We demonstrated that proliferation rate of low level BTG2 expression in MCF7 was strongly inhibited by the administration of tamoxifen. In postmenopausal breast cancer patients, androgens can be converted to mitogenic estrogens by aromatase in breast cancer cells. Based on these results, we hypothesized that BTG2 expression affects the sensitivity against aromatase inhibitior. Methods: We used tetracycline-inducible BTG2 expression model in MCF7 stably transfected with the human aromatase gene (MCF7/tet/aro) as in vitro models of aromatase-driven breast cancer. The effects of BTG2 expression and administration of anastrozole in breast cancer cells were assessed by proliferation assays. Results: Administration of androstendion increased 79.1% of cellular proliferation, suggested that introduced aromatase gene worked well. Elevated level of BTG2 mRNA expression by tetracycline treatment was confirmed by Quantitative-RTPCR. Anastrozole treatment (100nM) reduced 37.8% of cellular proliferation ability, whereas the concomitant administration of tetracycline and anastorozole reduced 59.0% of cellular proliferation. These results suggested that the inhibitory effect of anastrozol for cellular proliferation was enhanced under the condition of BTG2 expression. Conclusions: Our results suggested loss of BTG2 expression may be affects the sensitivity against aromatase inhibitor.
Expression (Exp) of FIP200 and Rb in breast cancer (BreastCA) metastasis (met) to the brain.
Authors: Hashemi Sadraei N. , Burgett M. , Ahluwalia M. S. , Tipps R. , Khosla D. , Weil R. , Nowaki A. , Prayson R. , Shi T. , Gladson C. 
Published: February 2017

222 Background: BreastCA is the 2nd leading cause of cancer deaths in women in the US. Although the outcome for BreastCA with brain met remains poor, there is significant variation in overall survival (OS). Yet, there are no markers or models to predict OS. FIP200 regulates several pathways. In the nucleus, it inhibits cell proliferation by promoting Rb-1 and p21, and in the cytoplasm it promotes cell survival by inhibiting Pyk2 and regulating autophagy. It has been reported that FIP200 gene is deleted or mutated in 20% of primary BreastCAs, and its Exp is correlated with Rb1 levels. FIP200 Exp, its cellular localization, and gene alterations have not been examined in brain met of any cancer. Methods: Brain met tissues of 21 BreastCA patients (pts) biopsied in our institution between 8/2000 and 3/2010 were obtained and Exp of FIP200 and Rb1 were analyzed. Biopsies were selected based on tissue adequacy and prior diagnosis (Dx) of invasive intra-ductal BreastCA. Immunohistochemistry (IHC) was used to evaluate the localization and Exp levels of FIP200 and Rb1 which in turn were tested as predictors of OS. Genetic alterations in FIP200 and Rb1 were examined after DNA extraction. Results: Median time from Dx to met was 23 (range 0-245) months (mos), and median OS from Dx was 43 (range 6-264) mos. Nuclear Exp of Rb1 in < 30% vs. ≥ 30% of cells were seen in 11 vs. 10 pts. Median OS was 39 (range 6-264) mos for Rb1 Exp < 30% and 47 (range 20-190) mo for Rb1 Exp ≥ 30%. Nuclear Exp of FIP200 in <20% vs. ≥ 20% of cells were seen in 13 vs. 8 pts. Median OS was 39 (range 6-264) mo for FIP200 nuclear Exp <20% and 45 (range 43-122) mo for FIP200 Exp ≥ 20%. DNA analysis of 11 pts for copy number variations and loss of heterozygocity (LOH) showed no deletion mutations in FIP200 or Rb1, loss of p53 in 4 of 11, ErbB2 (Her-2) amplification in 4 of 11, and no EGFR gene mutations. Conclusions: The nuclear Exp of Rb1 in brain met from invasive intra-ductal BreastCA may be linked OS. An expanded study is underway to define whether nuclear FIP200 in >20% of cells correlates with nuclear Rb and OS in BreastCA.
A pilot study of the decision-making process of seeking medical care in women diagnosed with large breast tumors.
Authors: Eggar J. M. , Lea C. S. , Bellin L. S. , Raab R. E. , Wong J. H. , Burke L. P. 
Published: February 2017

237 Background: Twelve percent of women diagnosed with invasive breast cancer in eastern NC present with large tumors (≥ 4 cm). The reasons for presentation with advanced cancer are not known and may include both social factors and tumor characteristics. Methods: The objective of this qualitative pilot study was to investigate the decision-making process of seeking medical care in women diagnosed with ≥ 4 cm breast tumors through in-depth interviews. Six female breast cancer patients treated at Brody School of Medicine completed in-depth qualitative semistructured interviews along with demographic questionnaires. The interviews, designed to uncover barriers and motivators to seeking breast cancer diagnosis and care, were recorded and transcribed verbatim. Results: Six women (aged 44-68) completed the interview process, three African Americans and three Caucasians. Mean tumor at diagnosis size was 11.2 cm (range 4-18 cm). Three women who lived alone hid breast cancer symptoms from their family; of these, two women had fungating tumors and one had nipple drainage for more than 1 year prior to diagnosis. Four women had health insurance. Two women reported being without insurance for more than 10 years and cited this as the primary reason for delaying care. Both insured and uninsured subjects delayed care due to fear of being a burden to family, financially or support wise. One woman delayed care due to fear of chemotherapy and radiation. Three women reported regular mammograms; two presented with fast-growing tumors, one had a chest wall tumor that was missed on mammography. Conclusions: Three of six patients presenting with locally advanced disease stated that they made a decision to delay medical care. Subjects’ lack of insurance, fear of cancer and cancer treatments, and concern for family were among reasons for delays. Qualitative approaches may be useful in studying factors that affect patient access to care. More research is needed on ways to improve access and empower women to seek care.
Determining the rate of tumor growth and decay in patients with metastatic breast cancer as an early efficacy endpoint: A study assessing ixabepilone efficacy.
Authors: Amiri-Kordestani L. , Jawed I. , Wilkerson J. , Stein W. D. , Bates S. E. , Swain S. M. , Fojo A. T. 
Published: February 2017

246 Background: Early efficacy assessment in drug development should help find new cancer therapies. We have developed a novel method to analyze tumor response to therapy by quantifying the rate of tumor regression (d) and growth (g). We have shown g is slower when pts are on effective therapy and that g correlates with survival (Stein et al, Oncologist 2008). We utilized this method to evaluate a phase III trial of capecitabine (CAP) ± IXA in second line therapy (Tomas et al, JCO 2007) and a three-cohort phase II trial in second and subsequent lines of therapy in pts with MBC consisting of (1) Daily X 5 IXA given to taxane (TAX)-naïve patients (Denduluri et al, JCO 2007); (2) Daily X 5 IXA in pts previously treated with TAX (Low et al, JCO 2005); and (3) Daily X 3 IXA in pts previously treated with TAX (Denduluri et al, Invest New Drug 2007). Methods: Using tumor measurements assessed by RECIST and a two-phase mathematical equation we determined d and g. Results: In the phase III study g was superior to PFS identifying a significant difference between the arms very early—before the 200th pt had enrolled. In an individual patient the g values could be estimated as early as the 3rd evaluation, long before tumor growth was observed clinically. IXA + CAP in second line (g = 0.0018) was more effective than CAP (g = 0.0023) at reducing g, and more effective (p=0.0085) than single agent IXA in the Phase II study (g = 0.0027). Single agent IXA was comparably effective (p=0.814) in reducing the g of tumors previously exposed to a TAX (g = 0.0032) as in reducing the g of TAX-naïve tumors (g = 0.0035), consistent with its development as an agent active in TAX-refractory disease. Unlike differences in g, the d of single agent IXA (0.118) was comparable to that of IXA+CAP (0.0074) suggesting differences were primarily driven by effect on the growth of residual tumor. Conclusions: Unlike PFS, an incremental measure of efficacy, g is a continuous variable and can more accurately assess differences between treatments. Because calculations of g are indifferent to assessment intervals, estimating a tumor’s g allows comparison of efficacy across trials.
Defining survival for patients with breast cancer with brain metastases.
Authors: Pathe N. P. , Khalid S. , Khan C. , Atem F. D. , Trombetta M. G. , Geyer C. E. 
Published: February 2017

258 Background: Brain metastases account for 100,000 to 170,000 cases per year in the U.S, the bulk being from breast and lung primaries. About 10-15% of breast cancer patients develop brain metastases and historically, their survival has been poor. Introduction of novel chemotherapeutic and biologic agents and newer radiation techniques in the past decade has led to better control of systemic disease raising the possibility of increasing incidence of brain metastases as well as better control of CNS disease. The aim of this study was to determine the survival of breast cancer patients with brain metastases in our practice in the last 10 years. Methods: This study was a retrospective chart analysis and we analyzed the charts of 18 patients with breast cancer who had developed brain metastases. The parameters analyzed included patient age at diagnosis of breast cancer and at development of brain metastases, receptor status and various treatment modalities used to control local as well as Metastatic disease. Results: The median survival time after adjusting for age at diagnosis of breast cancer, age at diagnosis of brain metastases and the number of brain metastases was 55 months. The time to death was analyzed using Cox proportional hazard model, adjusting for age and number of brain metastases. Age at diagnosis of breast cancer was significant with a p-value of 0.007 and the number of brain metastases was not significant with a p-value of 0.55. Using the Log Rank test, median survival for Her2neu positive patients was 71 months and for Her2neu negative patients was 58 months with a non-significant p value of 0.86. Review of treatment modalities revealed that six patients underwent surgical removal of metastases and 12 patients received WBRT. Average number of systemic treatments used was 6.7 including chemotherapeutic, biological and hormonal agents. Conclusions: In our practice, the overall survival of breast cancer patients with brain metastases was found to be 55 months after adjusting for age at diagnosis of breast cancer, age at diagnosis of brain metastases and number of brain metastases. Overall survival did not vary significantly with the number of brain metastases and Her2neu receptor status.
Pregnancy-associated breast cancer (PABC): Czech Young Breast Cancer Study Group Project 35.
Authors: Zimovjanova M. , Tesarova P. , Konopasek B. , Barkmanova J. , Brabec P. , Novotny J. , Pavlista D. , Petruzelka L. B. 
Published: February 2017

265 Background: Breast cancer (BC) is the most common cancer in women. 12% of BC occur in women age 20–34. BC is classified as “pregnancy associated” if it is diagnosed during pregnancy or within one year after the delivery (PABC). We propose two distinct subtypes of PABC: BC diagnosed during pregnancy and BC diagnosed post-partum. This distinction is important because epidemiologic data highlights worsened outcomes specific to post-partum cases. The safety of pregnancy after treatment of BC is an important issue for many young women. Current research does not indicate that pregnancy negatively affects survival. Methods: There are about 95 young women being diagnosed each year with BC in the Czech Republic. A project of clinical registry named “Project 35” was launched in 2005 with the aim to collect data on epidemiology of the disease in young women. The standardization of the multidisciplinary medical treatment, genetic counselling and psychosocial support should result in better clinical outcomes and improve the quality of life. Results: In our project (n=225) were referred 25 women with PABC, 9 patients with the diagnosis of breast cancer during the pregnancy, 16 patients within one year after the delivery. 2 patients underwent termination of the pregnancy (first trimester) before oncological treatment, in 2 patients anthracycline-based chemotherapy was administered (second trimester), and in 5 patients were induced preterm delivery (third trimester). After delivery we followed standard therapeutic guidelines. All patients are alive but three of them have metastatic disease. From 16 women treated for post-partum BC, 11 patients have complete remission, 2 are alive with metastatic disease, 1 is recovering after the surgery for local recurrence and 2 patients died due to progressive disease. 8 women are BRCA1/2 carriers. 8 women after the successful treatment of breast cancer have delivered of healthy children and are in a complete remission, despite 1 of them with local reccurence of breast cancer. Conclusions: PABC is rare situation, which needs to be managed individually. These patients should be treated under the supervision of the Oncological Centres. Project 35 is useful framework for the counselling in PABC.
Final results of NKTR-102, a topoisomerase I inhibitor-polymer conjugate, in patients (Pts) with pretreated metastatic breast cancer (MBC) demonstrating significant antitumor activity.
Authors: Garcia A. , Awada A. , Chan S. , Jerusalem G. H. M. , Coleman R. E. , Huizing M. T. , Mehdi A. , O'Reilly S. M. , Hamm J. T. , Barrett-Lee P. J. , Cocquyt V. , Sideras K. , Young D. E. , Brown M. , Zhao C. , Hannah A. L. , Leung A. C. F. , Masuoka L. K. , Perez E. A. 
Published: February 2017

269 Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate with reduced peak concentration and a continuous concentration profile. Methods: This was an open-label phase II study in MBC pts following PD on a taxane (T). Pts were randomized to NKTR-102 given IV at 145 mg/m2 over 90-min every 14 or 21 days. Efficacy endpoints included ORR by RECIST v1.0; PFS and OS. Results: 70 pts (35 per schedule) randomized from Feb 2009 to May 2010 (median follow-up: 10 mo). Median age: 55 (range 33–83). ECOG PS 0/1: 40%/60%. Neoadjuvant and/or adjuvant: 74%. Median number of prior cytotoxic regimens for metastatic disease: 2. All pts had received prior T: 7% (adjuvant); 93% (metastatic). 89% had received prior anthracyclines (A): 63% (adjuvant); 26% (metastatic). 63% had received prior AT only (23% in MBC); an additional 26% had received prior AT/capecitabine (ATC). 61% were ER/PR+; 30% had TNBC; 86% had visceral metastases. Median PFS for q14d, q21d and overall were 3.5 mo, 5.3 mo and 4.6 mo. Median OS for q14d, q21d and overall were 8.8 mo, 13.1 mo and 10.3 mo. Toxicity was manageable, with diarrhea as the most common grade 3+ toxicity, with median time to onset ∼3 mo. Discontinuation from study drug due to AEs: 20%/14% for q14d/q21d. Neuropathy was absent; alopecia was minimal (20%/11% grade 1–2 for q14d/q21d). Conclusions: NKTR-102 demonstrates significant anti-tumor activity in pts with advanced MBC, including poor prognosis pts with TNBC and having received prior ATC. A phase III study is being planned in patients with MBC previously treated with taxanes. [Table: see text]
Survival of patients with locally advanced triple-negative breast cancer after neoadjuvant platinum-containing chemotherapy: Experience of a single institute.
Authors: Ibrahim E. A. 
Published: February 2017

274 Background: Primary systemic chemotherapy is a standard approach to treating women with locally advanced breast cancers, with higher survival rates reported among patients who attain a pathologic complete response. Triple-negative breast cancer is a special biological entity that remains major challenge to oncologist. Around 12%-20% of breast cancers are triple negative. The current phase II study was conducted to evaluate the pathological complete response (pCR) using cis-platinum containing regimen as neoadjuvant chemotherapy in locally advanced triple negative breast cancer. Methods: Eighteen women with stage III triple negative breast cancer who were recruited between July 2007 and February 2010 at King Fahad Specialist Hospital, Dammam, Saudi Arabia. Neoadjuvant chemotherapy consisted of 4 cycles of AC or FEC 100, followed by 4 cycles consisted of docetaxel-cisplatin every 3 weeks. Primary end point was pathological complete response. Results: Median age: 49 y (24-70); premenopausal: 16; 25% were below 35 years of age; Median tumor size: 9 cm (3.5-19); Grade III: 15; Stage IIIA: 3, IIIB:14, IIIC:1; all but 2 had positive nodes at diagnosis (89%). Clinical evaluation of response by RECIST criteria pre surgery: OR: 17/18 (94%), CR: 9 (50%); PR: 8 (44%).The second sequence with D-Cis-T doubled the rate of clinical CR obtained with AC/FEC. One patient was not operated due to disease progression. Pathological assessment, revealed that 8 (47%) pts had no residual invasive carcinoma in the breast; 3 (18%) had residual occasional scattered tumor cells less than 5 mm (pT1a); 10 (59%) had negative nodes; 8 achieved CpR and 2 nCpR. Patients with residual invasive component and/or nodal involvement had high baseline Ki 67 level. After a median follow up of 24 months, cumulative overall survival at 24 months is 88.9% for whole group. Cumulative overall survival in relation to response was 100% for patients who achieved pCR while overall cumulative survival rate for patients without pCR was 83.3% without statistical significance. Conclusions: This cisplatin based neoadjuvant chemotherapy regimen was well tolerated and achieved a high rate of pCR/npCR.
Albumin-bound paclitaxel (ab-pac) versus docetaxel for first-line treatment of metastatic breast cancer (MBC): Final overall survival (OS) analysis of a randomized phase II trial.
Authors: Gradishar W. J. , Krasnojon D. , Cheporov S. V. , Makhson A. , Manikhas G. M. , Clawson A. , Bhar P. 
Published: February 2017

275 Background: We previously reported the results of a phase II study evaluating the efficacy and safety of three different dosing regimens of ab-pac and docetaxel for the first-line treatment of MBC (Gradishar et al. J Clin Oncol. 2009;27:3611-3619). Here we report final OS outcomes. Methods: Patients (N = 300) with previously untreated MBC were randomized to 1 of 4 treatment arms (arms A–D listed in table). A step-down statistical approach was used for pairwise comparisons of treatment groups. Results: Patients (N = 300) with previously untreated MBC were randomized to 1 of 4 treatment arms (arms A–D listed in table). A step-down statistical approach was used for pairwise comparisons of treatment groups. These OS data were consistent with the investigator assessment of overall response rates (ORR) and progression-free survival (PFS) that were previously published. Rates of grade (gr) 3 sensory neuropathy (SN) were 21%, 9%, 22% and 12%, respectively in arms A, B,C, and D (p= 0.082). There were no cases of gr 4 SN. The median times to improvement to ≤ gr 2 SN were 22, 22, and 20 days for arms A, B, and C and 37 days for arm D. Gr 3/4 neutropenia occurred less frequently with ab-pac vs docetaxel (gr 3: 39, 20, 35, and 19% in arms A,B,C, and D, respectively; gr 4: 5, 5, 9, and 75%, p < .001 for gr 4). Conclusions: Ab-pac qw 3/4 at 150 mg/m2 resulted in a 33.8 mo OS, a longer OS than historically achieved with taxane monotherapy in MBC. The 150 mg/m2 qw 3/4 dosing regimen provided the best clinical outcome in this phase II trial in patients with MBC. [Table: see text]
Evaluation of recurrence score and traditional clinicopathologic metrics in a large ER-positive, lymph node–negative patient cohort.
Authors: Baehner F. L. , Liebermann N. , Shak S. , Klang S. , Yoshizawa C. , Lior s. , Siegelmann-Danieli N. 
Published: February 2017

30 Background: The 21 gene Recurrence Score (RS) assay provides prognostic and predictive info for ER+ breast cancer. In a large cohort of ER+, HER2 normal, lymph node negative (LN-) patients, the distribution of RS and RS groups, within categories of patient age, tumor size, grade, and joint categories (e.g., tumor size versus patient age), were examined. Methods: 2,097 pts from Clalit Health Services (CHS) and 484 from Maccabi Health Services (MHS) in Israel, had the RS ordered between 1/08-6/10. 1864 were LN-, ER+ and HER2 nrml (LN- grade 3 tumors of MHS pts were required to be <2 cm). Pt age, tumor size and grade were obtained for 100%, 99% and 82%. Distributions of RS were compared among categories of the traditional factors and Spearman correlation coefficients (and 95% CI) were calculated to assess the association between the RS and them. Results: 99.3% were female. Standard distributions by age were: 23-40 yo, 3.2%; 40-49 , 16.5%; 50-59, 30.4%; 60-69, 32.8%; 70-85, 17.1%. By tumor size: <1 cm, 12.5%; 1-2cm, 65.8%; >2-3cm, 17.3%; >3cm, 4.5%. By grade: 1, 18.1%; 2, 63%; 3, 18.9%. 79.7% were ductal & 12.5% lobular. 81.9% were IHC PR+. Spearman correlation coefficients (and 95% CI) for continuous RS with standard metrics: age, -0.09 (-0.13, -0.04); tumor size (cm), 0.07 (0.02,0.12); grade, 0.33 (0.28, 0.37). Pts <50 yo, 14.2% had high RS disease (dz); ≥50 yo 10.3% had high RS dz. In tumors ≤2 cm, 16% had high RS dz; > 2 cm 30.7% had high RS dz. Of grade 1 tumors 1.4% had high RS dz and 30.7% had intermediate RS while 22.8% of grade 3 tumors had low RS dz. 7.5% of PR+ tumors had high RS dz and 20.1% of PR- tumors had low RS dz. Joint categories will be presented. Conclusions: There is a range of RS biology across patient age, tumor size and grade. The RS cannot be predicted by clinicopathologic variables. [Table: see text]