bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
Authors: James Edward Samuel , Chung Gina , Sowers Noelle Marie , Clark Mary Beth , Lilian Rebecca , Abraham Gineesha , Chmael Susan , Cappiello Michelle , DiGiovanna Michael , Hofstatter Erin Wysong , Sanft Tara Beth , Israel Gary M. , Pusztai Lajos , Harris Lyndsay , Abu-Khalaf Maysa M. 
Published: February 2017

154 Background: Synergy between histone deacetylase inhibitors and 5-fluorouracil is thought to be due to down regulation of thymidylate synthase. Study objectives are to assess maximum tolerated dose (MTD), dose limiting toxicities (DLT) and objective response rate of vorinostat (V) in combination with capecitabine (C). Secondary aims are pharmacodynamics of V. Methods: Cohorts of 3-6 patients (pts) were enrolled on a 3+3 dose-escalation phase to assess MTD of escalating doses of oral C (1500/1800/2000mg) with V 200 mg BID on days 1-7 and 15-21 of a 28 d cycle. 10 pts enrolled on dose expansion phase and treated at MTD. Pts received a “run in” treatment of V for 5 d and pre/post V biopsy (bx) collected when feasible. DLT was defined as ≥ grade 3 non hematological toxicity, grade 4 thrombocytopenia, grade 4 neutropenia > 5 d, grade 4 febrile neutropenia requiring hospitalization, QTc >500ms,or treatment delay > 2 weeks from toxicity. Microarray analysis was performed using Illumina HT-12 gene arrays on pre/post bx from 4 pts. Results: 23 ptswith median age 51 (range 33-69) were treated: 8 pts at 1500/200mg, 5 pts at 1800/200mg, and 10 pts treated on dose expansion phase at 1500/200mg. Median # of prior lines of chemotherapy was 2 (range 0-7). 3 pts are still on study. Median # of cycles on study were 2 (range 1-42). Cycle 1 DLT was grade 3 fatigue in 2 pts treated on 1800/200mg, and in 1 pt treated on 1500/200mg. Other grade 3/4 toxicities are summarized in the Table. 14 pts are evaluable for response (12 pts at 1500/200mg and 2 pts at 1800/200mg). No objective responses were seen, 3 pts had stable disease > 6 months (1 pt completed 42 cycles). All post V bx converged on principal components analysis. Changes in pathways involved in extracellular matrix and TGFb pathway were noted. Conclusions: DLT of C concomitant with V was fatigue. MTD was 1500 mg C combined with 200 mg V BID. Combination has modest clinical activity. Gene expression profiles suggest consistent pathway modulation with V. Clinical trial information: NCT00719875. [Table: see text]
Patient-reported physical, emotional, and social functioning in advanced breast cancer: Insights from BOLERO-2.
Authors: Yardley Denise Aysel , Hortobagyi Gabriel N. , Lebrun Fabienne , Beck J. Thaddeus , Neven Patrick , Baselga Jose , Petrakova Katarina , Dakhil Shaker R. , Sabatini Silvia , Komorowski Anna , Chouinard Edmond Emilien , Young Robyn R. , Gnant Michael , Pritchard Kathleen I. , Zhang Jie , Ziemiecki Ryan , Brechenmacher Thomas , Taran Tanya , Sahmoud Tarek , Noguchi Shinzaburo 
Published: February 2017

155 Background: The phase III BOLERO-2 study at 18 months’ median follow-up showed that everolimus (EVE) + exemestane (EXE) significantly improved progression-free survival (PFS) vs EXE alone in 724 patients with hormone receptor–positive (HR+) advanced breast cancer (ABC) with recurrence/progression during/after nonsteroidal aromatase inhibitor (NSAI) therapy. A higher rate of grade 3/4 adverse events was noted with EVE + EXE but was not associated with deterioration in quality of life (QOL) based on the EORTC QLQ-C30 Global Health Status scale. Additional patient-reported post hoc analyses of QOL are reported herein. Methods: During BOLERO-2, QOL (EORTC QLQ-C30 and QLQ-BR23) was assessed at baseline and q 6 wk thereafter until progression or discontinuation. Physical, emotional, and social functioning subscales of QLQ-C30 were analyzed. Time to definitive deterioration (TTD) was defined based on either a 5% (protocol-specified) or a 10-point (more stringent) decrease from baseline for each subscale and analyzed by Kaplan-Meier methods. The difference between treatments was assessed by a log-rank test stratified by randomization factors. Results: QLQ-C30 compliance was >80% at week 48. Among the 3 protocol-specified QLQ-C30 subscales, analyses based on a 5% decrease in QOL showed a longer TTD for both physical and emotional functioning in the EVE + EXE group vs EXE alone (log-rank p = 0.0120 and p = 0.0277, respectively). The TTDs for social functioning were similar in both treatment arms (log-rank p = 0.3374). Analyses based on a 10-point decrease indicated a longer TTD for physical functioning in the EVE + EXE group (15.2 mo) vs EXE alone (9.7 mo; log-rank p = 0.0211). The TTDs for emotional and social functioning were similar between EVE + EXE and EXE alone: 13.9 vs 13.8, respectively (log-rank p = 0.4023), and 11.5 vs 9.5, respectively (log-rank p = 0.2507). Conclusions: The treatment goal for ABC is to maximize clinical benefit with minimal negative effects on QOL. These additional BOLERO-2 QOL analyses confirmed that the more than doubling of PFS with EVE + EXE was accompanied by maintained physical, emotional, and social functioning compared with EXE alone in patients with HR+ ABC progressing after NSAI. Clinical trial information: NCT00863655.
Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study.
Authors: Yardley Denise Aysel , Krop Ian E. , LoRusso Patricia , Robert Nicholas J. , Mayer Musa , Abidoye Oyewale O. , Lai Catherine , Yoo Bongin , Perez Edith A. 
Published: February 2017

166 Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1. Few T-DM1 data are available in settings approximating clinical practice. We present safety and efficacy data from T-PAS, an expanded access study of T-DM1 in patients (pts) with previously treated HER2-positive MBC. Methods: T-PAS is a US multicenter study of T-DM1 (3.6 mg/kg q3w) in HER2-positive (IHC 3+ or FISH/CISH+) locally advanced or MBC. Key eligibility criteria: prior anthracycline and taxane; prior capecitabine or 5-FU and ≥2 HER2-directed agents (including trastuzumab and lapatinib) for MBC; LVEF ≥50%. Primary endpoint: safety; secondary endpoint: investigator-assessed objective response rate (ORR) in pts with measurable disease. Safety was assessed on day 1 of each cycle; ECHO/MUGA scans were every 12 weeks. Results: This analysis includes 215 pts enrolled in May 2010–Sep 2011 (data cutoff 7/31/2012). Pts received a median of 7 prior systemic MBC therapies (range 1–23) with a median cumulative anthracycline dose of 240 mg/m2(range 6–2645). At baseline, median LVEF was 60% and 50% of pts had investigator-reported cardiovascular disease. Median follow-up was 5.9 months (range 0.1–25.3); median T-DM1 duration was 5.0 months (range 0–23) with 15.8% receiving >18 cycles. ORR was 25.6% (42/164). Rate of grade ≥3 AEs was 43.7% and of SAEs of any grade was 18.1%. Most common all-grade AEs were fatigue (50.7%), nausea (36.3%), and headache (24.2%). Most common grade ≥3 AEs were thrombocytopenia (7.9%), fatigue (4.7%), and increased aspartate aminotransferase and anemia (each 3.7%). There were no grade ≥3 bleeding events. Cardiac dysfunction (primarily asymptomatic decreases in LVEF) was reported in 8 pts (3.7%); 4 were grade ≥3, 3 resulting in T-DM1 discontinuation. Conclusions: In this study that more closely reflects the real-world setting, the safety profile of T-DM1 was similar to that previously reported in conventional clinical trials, with no new safety signals. In this pretreated population (median of 7 prior therapies for HER2-positive MBC), significant activity was observed. Clinical trial information: NCT01120561.
Kinase-sensing system to identify the oncogenic phospho-fingerprint of breast cancer.
Authors: Mori Miki , Chen Zhongzhong , Boudreau Aaron , van't Veer Laura , Coppe Jean-Philippe 
Published: February 2017

23 Background: Kinases and their substrates harness myriad critical molecular pathways. A new highly valuable assay would be one detecting the true active state of phospho-signaling networks. To address this technological and knowledge gap, we developed a semi-high throughput sensing system that monitors the catalytic activity of kinases using peptides as phosphorylation targets/probes. We used this assay to evaluate the presence of dysfunctional kinases in biological extracts and identify oncogenic phospho-signatures prevalent in breast cancer. Methods: We developed a human kinase protein and peptide repertoire computationally curated from thousands of publications. Out of the 2,702 validated peptide targets and 6,173 kinase-substrate nodes we compiled, we chose a subset of 151 biological peptides predicted to specifically report on tyrosine / serine / threonine kinases, including EGFR, ERK, AKT, SRC, ABL. Along with 91 control peptides, we tested a total of 242 peptides in a luminescence ATP-consumption assay for their ability to report on the kinases’ activity. The assay was further validated using an isogenic culture model of basal like breast cancer (HMT-3522 S1 and T4-2), and cell lines harboring various oncogenic alterations (MDA-MB-231, MCF7, T47D, AU565, ZR75.1, SKBR3). Results: The differential phosphorylation activity of recombinant kinase enzymes was successfully detected in time course, dilution and inhibitor experiments. The increased presence of (hyper-) activated SRC, EGFR, AKT or ABL kinases observed by western blots in subsets of breast cancer cells, was selectively, repeatedly and specifically detected using the peptide-based kinase assay. Significantly altered peptide-phosphorylation patterns were successfully integrated into signatures using gene expression microarray-like analysis, revealing the breast cancer-associated map of phosphorylation circuits. Conclusions: This assay is suitable to comprehensively capture the activity of kinase signaling networks. We will now use this functional proteomic assay to identify the active, oncogenic kinome of breast cancer, with the objective to improve clinical guidance and individualize breast cancer patients’ therapy.
Cost-benefit of recurrence score–guided treatment using an Oncotype DX 21-gene assay: A single institution analysis.
Authors: Abbi Kamal Kant Singh , Shahid Nauman , Hameed Muhammad Khurram , Fink Brian , Gaba Colette , Mohamed Iman 
Published: February 2017

29 Background: In 2010 the National Comprehensive Cancer Network recommended a 21-gene assay recurrence score (RS) to aid in the adjuvant treatment decision among patients with estrogen receptor positive, lymph node negative early stage breast cancer. Early-decision impact studies show that the RS can reduce overall chemotherapy use by 27%. This study was performed to assess the cost-benefit of the test for the patients diagnosed and treated an academic institute before 2010. Methods: Data from early breast cancer estrogen-receptor–positive and lymph-node–negative patients (n = 87), who were diagnosed and treated at our center from 2004-2010 were analyzed. All patients had the 21-gene recurrence test done to guide in their management. Cost of chemotherapy, adverse effects, and supportive care costs were calculated from previously published articles. Results: 66 patients with stage I breast cancer and 21 patients with stage II were analyzed. All but one patient had a tumor size more than 5mm. In total, 27 patients received chemotherapy. Characteristics of patients receiving chemotherapy are shown in the table. Cost of 21 gene recurrence score assay was $4,000. Savings for each patient who did not receive chemotherapy was $21,715 after accounting for cost of the test. The total savings for 60 patients who did not receive chemotherapy was $1,302,900. Conclusions: Use of the 21-gene assay in patients with early stage lymph node negative breast cancer improves health outcomes by avoiding chemotherapy-related adverse events. It also appears to add no incremental costs. This study emphasizes the cost-saving potential of the Oncotype Dx 21 gene assay. [Table: see text]
Breast cancer patients’ risk perceptions and treatment values following surgical consult.
Authors: Kaiser Karen , Cameron Kenzie A. , Stolley Melinda , Bethke Kevin P. , Hansen Nora M. , Jeruss Jacqueline Sara , Clayman Marla L. , Khan Seema Ahsan 
Published: February 2017

36 Background: Contralateral breast cancer (CBC) is the most common second primary cancer in breast cancer patients. The 10-year risk of CBC for patients with locally invasive or intraductal disease is approximately 6%. However, a recent study reported that prior to surgical consult newly diagnosed breast cancer patients without a BRCA mutation estimated their 10-year CBC risk to be 31.4%. We sought to evaluate breast cancer patients’ perceived risk of future cancer and their treatment values following surgical consult. Methods: Women diagnosed with ductal carcinoma in-situ or stage I-III invasive breast cancer were interviewed in the period between surgical consult and surgical treatment. Participants completed the Perceived Risk Questionnaire (PRQ) and the Values Scale. The PRQ contains 5 questions to assess perceived likelihood of future cancer on a 5-point scale (1 = not at all likely, 5 = very likely). For each question, women also estimate the likelihood of cancer in the next 10 years as a percentage from 0 to 100. The Values Scale measures the importance of 11 treatment-related values (e.g., How important is it to you to keep your breast?) on a 10-point scale (1 = not at all important, 10 = very important). Results: Interviews were completed with 20 patients (mean age 54.7 years) without a known BRCA mutation. On the Values Scale, women identified minimizing the chance of cancer elsewhere in the body (mean=9.2), in the other breast (mean = 9.1), and in the same breast (mean = 8.8) as most important. Patients estimated their 10-year risk to be 13.6% for CBC, 14.2% for breast cancer appearing in the same breast, and 19.6% for cancer appearing elsewhere in the body. One-fourth of participants believed they faced at least a 50% chance of encountering breast cancer again in the next 10 years. Conclusions: Women in this study reported lower perceived risk of CBC than in a prior study of perceived risk prior to surgical consult, thus suggesting that the surgical consult may lead to a reduction in perceived risk. Nonetheless, participants’ estimated their 10-year risk of CBC to be twice the actual estimated risk. Our findings indicate a need for additional patient education about CBC risk.
The accuracy of preoperative U.S.-guided vacuum-assisted breast biopsy (VABB) in determining ER, PgR, HER2, and Ki67 status in early breast cancer.
Authors: Kamei Keitaro , Fujita Takashi , Ito Toshikazu , Yagata Hiroshi , Ono Minoru , Watanabe Ryoji , Gomi Naoya , Onishi Kiyoshi , Sakamoto Naomi , Hashimoto Hideyuki , Taguchi Tetsuya , Nakayama Takahiro ,   Japan Association of Breast and Thyroid Sonology (JABTS) Interventional Study Group
Published: February 2017

37 Background: The intrinsic subtypes are important in the management of patients with early breast carcinoma; however, there have been only a few reports about the accuracy of preoperative subtyping by the preoperative ultrasonography guided vacuum-assisted breast biopsy (U.S.-guided VABB). The aim of this study was to evaluate concordance of the status of ER, PgR, HER2, and Ki67 between U.S.-guided VABB and subsequent surgical specimen. Methods: We retrospectively assessed the concordance of ER, PgR, HER2 and Ki67 status between U.S.-guided VABB and surgical specimen. The patients (n=228) underwent surgical treatment without neoadjuvant chemotherapy at the institute of Japan Association of Breast and Thyroid Sonology (JABTS) Interventional study Group from 2009 to 2012. All the US-guided VABB were performed using 8 or 11-gauge Mammotome or 10-gauge VACORA. The ER and PgR status were determined by IHC and HER2 expression status was tested by both IHC and FISH. The agreement on ER, PgR, HER2 and Ki67 status were evaluated by the absolute concordance rate and the kappa statistic values. Results: The concordance rate of ER, PgR, and HER2 status between U.S.-guided VABB and surgical specimens were 96.4% (134/139), 89.2% (124/139), and 96.3% (130/135), respectively (kappa statistic value of 0.90, 0.77, and 0.84), and the agreement of Ki67 level was 89.6% (112/125) with a Kappa statistic value of 0.79. The concordance rate of the intrinsic subtypes was 84.0% (105 of 125 cases). Conclusions: The judgment of ER status, and HER2 status by preoperative U.S.-guided VABB can be used with confidence to determine the treatment strategies based on molecular subtypes.
Biomarkers predictive for pathologic response to neoadjuvant docetaxel/cyclophosphamide chemotherapy in primary breast cancer.
Authors: Shimada Kazuhiro 
Published: February 2017

42 Background: Since docetaxel /cyclophosphamide chemotherapy (TC) has proven to be superior to anthracycline/cyclophosphamide (AC) in U.S. Oncology Research Trial 9735, TC has been widely used for treating patients with breast cancer. However, taxane-specific adverse events like neuralgia and edema can’t be ignored. Thus, we performed neoadjuvant study with TC to clarify biological markers of this regimen. Methods: 79 patients with invasive breast cancer received TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2, q3w for 4 courses) at the neoadjuvant setting and underwent surgical treatment. Before treatment, the clinic-pathological and immunohistochemical markers (ER, PgR, HER-2, Ki-67, p53, topoisomerase IIα, ClassIII β tubulin, CK5/6, EGFR) were examined with core-needle biopsy specimens. The correlation between the pathological response and expressions of markers was investigated. Results: 33 patients (41.8%) achieved quasi-pathological complete response (QpCR). Univeriate analysis revealed that ER (p < 0.001), PgR (p = 0.007), Ki-67 (p = 0.022) and classIII β tubulin (p = 0.032) were associated with QpCR. Only ER (p = 0.050) and classIII β tubulin (p = 0.028) remained with a statistical significance at multivariate analysis. Subgroup analysis revealed that the negativity of CK5/6 and/or EGFR was correlated with QpCR in the triple negative subtype. Conclusions: ClassIII β tubulin had a specific predictive value for pathological response of TC in addition of ER, PgR and Ki-67. Sub-grouping is important for treating triple-negative breast cancer.
Screening in the high-risk populations: Stage of breast cancer when detected by combination imaging with MRI and mammogram.
Authors: Carpenter Kendall W. , Merritt Mindy L. , Gromet Matthew , Chambers Karinn Marie , Sarantou Terry , Flippo Teresa , Fisher Julie Gottlieb , White Richard L. 
Published: February 2017

44 Background: Screening patients at high-risk for the development of breast cancer consists of MRI and mammography. This retrospective review of screening MRIs in patients designated as high-risk for the development of breast cancer--based on family history alone or a calculated lifetime risk of ≥ 20%--seeks to determine the utility of MRI screening in the detection of early-stage breast cancer. The primary outcome evaluated was stage of malignancy detected through screening imaging.  Methods: Results of screening imaging performed between 1/1/08 and 12/31/11 were retrospectively reviewed. Patients who had a personal history of breast cancer were excluded. Remaining screens were categorized based on the following criteria: family history, BRCA mutation or high-risk as calculated by risk assessment tools. Screens with corresponding core biopsies were evaluated for the following: previous imaging obtained, core biopsy pathology and pathologic staging. Results: 118 patients met inclusion criteria and had a subsequent biopsy as a result of screening. Resultant pathology was 75 (64%; 75/118) benign lesions, 19 (16%; 19/118) atypical lesions, and 24 (20%; 24/118) malignant lesions. Of the 24 malignant lesions, 1 (4%; 1/24) were found to be node-positive at the time of surgical staging, and, 23 (96%; 23/24) were node-negative. Conclusions: Four percent (1/24) of patients undergoing high-risk screening had nodal disease at surgical staging, which compares favorably to historical rates of approximately 30% node-positive disease at diagnosis (Krag DN et al., NSABP B-32). Therefore, this study shows that screening high-risk patients can decrease the nodal-positivity rate.
Ten-year outcomes of accelerated partial breast irradiation compared with whole breast irradiation: A matched-pair analysis.
Authors: Wobb Jessica , Wallace Michelle , Shah Chirag , Ye Hong , Jawad Maha Saada , Marvin Kimberly , Grills Inga S. , Chen Peter Y 
Published: February 2017

55 Background: Breast conserving therapy (BCT) represents a standard of care in the management of early stage breast cancer; while adjuvant radiation therapy was traditionally delivered using whole breast irradiation (WBI), accelerated partial breast irradiation (APBI) offers an alternative to WBI that shortens the duration of treatment and may improve toxicity profiles and quality of life. The purpose of this analysis is to compare clinical outcomes of patients treated with WBI versus APBI. Methods: A total of 3,009 patients were treated with BCT at single institution between 1980 and 2012 with 2,528 patients receiving WBI and 481 patients receiving APBI (interstitial or balloon-based). A matched-pair analysis was performed with patients matched according to age (+/- 3 years), T stage (Tis vs T1 vs T2), and estrogen receptor (ER) status (+/-). All patients had a minimum of 12 months of follow up. A total of 247 matches were made with clinical outcomes compared using the Kaplan-Meier method. Results: Mean follow-up was 8.1 years for WBI vs. 7.8 years for APBI (p<0.001), a difference of less than 4 months. There were no differences with respect to age (p=0.88), tumor stage (p=1.0), or ER status (p=1.0). Long-term cosmesis was good to excellent in 94% vs. 95% of patients (p=0.78). WBI patients demonstrated a trend for slightly larger tumors (13.0 vs. 11.4 mm, p=0.06). At 10 years, no difference in ipsilateral breast tumor recurrence (4% vs. 4%, p=0.11), regional recurrence (1% vs. 1%, p=0.20), distant metastases (3% vs. 6%, p=0.47), disease free survival (93% vs. 91%, p=0.10), or contralateral breast failure (9% v. 3%, p=0.06) was noted when comparing WBI and APBI. In addition, 10 year cause-specific survival (94% v. 93%, p=0.72) and overall survival (83% vs. 75%, p=0.34) were similar. Conclusions: At 10 years, no differences in locoregional recurrence, distant metastasis or survival were found between patients undergoing whole breast irradiation or accelerated partial breast irradiation using interstitial catheter or balloon-based brachytherapy. These data represent one of the only APBI series with prolonged follow-up and show similar outcomes in a matched group of patients undergoing WBI or APBI.