bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the efficacy of chemotherapy drugs for the treatment of triple-negative breast cancers.
Authors: Zoghi Behyar , Ravdin Peter 
Published: February 2017

107 Background: Approximately 15-20% of all breast cancers account for triple-negative breast cancers that exhibit aggressive, distinct metastatic pattern and poor prognosis. More than 50% of patients with triple negative breast cancers develop chemoresistance and do not respond to chemotherapeutic drugs, leading to early relapse and shorter survival. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious cancer drugs. Methods: Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Results: Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Since miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that they represent more attractive targets than the single gene or gene product that is the target of conventional cancer treatments that are typically prone to drug resistance. Supporting this, we have recently demonstrated that miRNAs can be systemically delivered to treat breast cancer lung metastasis without any hepatotoxicity. In addition to being a potent therapeutic regimen, our preliminary analyses reveal that miRNAs can be bonafide early prognostic markers to monitor treatment response to specific drugs in triple-negative breast cancers. Conclusions: Taken together, these findings suggest that miRNA can serve as potent therapeutic adjuvants and although the data content of miRNA profiles is far less than that of gene expression profiles, by virtue of their ability to modulate entire spectrum of genes and pathways miRNAs have potential to be better classifiers for the prognosis and response to treatment of cancers. We believe that the identification of miRNAs that mediate chemoresistance could lead to more efficient treatment selection at the patient level and an improved response rates at the population level.
Characterization of responders versus nonresponders to the anti-estrogen agent fulvestrant: A retrospective cohort study.
Authors: Bhusal Santosh 
Published: February 2017

117 Background: Patients with breast cancer often benefit from targeted endocrine therapy with estrogen receptor antagonists. However, the duration of therapeutic response to these agents is variable. We investigated several clinical variables that may potentially affect the duration of response to fulvestrant in the setting of metastatic disease. Methods: A retrospective cohort analysis was done in 137 patients who received fulvestrant between 2000 and 2011 at Moll Cancer Center at Fairview Hospital and Cleveland Clinic Cancer Center. Several patient variables e.g. degree of estrogen receptor positivity, BMI etc. were analyzed. The RECIST 1.1 criteria was used to measure disease activity. Clinical benefit (i.e., responsiveness) was defined as complete response, partial response or stable disease at 24 weeks of therapy. 57 patients had clinical benefit whereas 80 did not. The clinical variables were then compared between the two groups using Chi square test, Fisher's exact test and Wilcoxon’s rank sum test. A multivariable logistic regression model was then used to assess the association. Results: Patients who were responders exhibited a significantly higher proportion of bone and/or soft tissue only metastases than non-responders (51% vs. 24 %, p= 0.001). They also appeared to be older (mean age ± SD: 64.1 ± 12.2 vs. 60.2 ± 13.2, p=0.044) and had prior aromatase inhibitor sensitiveness (83% vs. 56, p=0.006). However, in multivariate and logistic regression analyses, the site of metastases was found to be the only significant predictor of response. Patients with bone and/or soft tissue only metastases were more likely to be responders than patients with visceral metastases (OR= 2.883 [95 % CI= 1.313 - 6.328], P= 0.012; OR: 3.325 [95% CI, 1.600-6.908], p=0.001, respectively). Conclusions: In metastatic breast cancer, patients with bone and/or soft tissue only metastases were more likely respond to fulvestrant therapy than those with visceral metastases.
Use of disseminated tumor cells to predict outcome in patients with stage I-III breast cancer.
Authors: Gainer Sarah Marie , Krishnamurthy Savitri , Bhattacharyya Anirban , Lodhi Ashutosh , Hall Carolyn S. , Bedrosian Isabelle , Kuerer Henry Mark , Lucci Anthony 
Published: February 2017

119 Background: Published studies from Europe have shown the presence of disseminated tumor cells (DTCs) to independently predict outcomes in patients with non-metastatic breast cancer. The purpose of this study was to assess the experience with DTCs at a tertiary cancer center and to see if these cells indeed predict outcomes in patients with stage I-III breast cancer. Methods: Clinical stage I-III breast cancer patients seen at a single tertiary cancer center provided consent to participate in an IRB-approved study involving collection of bone marrow (5 ml x 2 tubes) at the time of surgery for their primary breast cancer. DTCs were assessed by anti-CK antibody cocktail (AE1/AE3, CAM5.2, MNF 116, CK 8 and 18) following cytospin. A positive result was defined as the presence of one or more cells per 5 ml of bone marrow. Statistical analyses used chi-square and Fischer’s exact tests. Results: Three hundred and sixty-six patients were prospectively enrolled. Mean age was 53 years. Median follow-up was 32 months. DTCs were identified in 109 patients (30%). Ten percent of patients with DTCs (11/109) and 3% of patients without DTCs (8/257) died (p = 0.009). Overall survival (OS) in patients with DTCs was 30 months vs. 31 months in those without DTCs. DTCs did not predict relapse free survival (P=NS). On multivariate analysis the presence of DTCs was an independent predictor of worse overall survival (p < 0.0001). No correlation was observed between the presence of DTCs and lymph node metastases and/or other clinicopathologic variables. Conclusions: The presence of DTCs was an independent predictor of worse OS in patients with stage I-III breast cancer. Consideration should be given to the utilization of DTCs as predictors of outcome in clinical practice.
Comparison of the incidence of peripheral neuropathy (PN) with eribulin versus ixabepilone (IXA) in metastatic breast cancer (MBC) patients: A randomized phase II study.
Authors: Vahdat Linda T. , Garcia Agustin , Vogel Charles L. , Pellegrino Christine M. , Lindquist Deborah L. , Sparano Joseph A. , Gopalakrishna Prashanth , Iannotti Nicholas 
Published: February 2017

121 Background: Eribulin mesylate is approved for patients (pts) with MBC who have previously received ≥2 chemotherapeutic regimens for metastatic disease including an anthracycline and taxane in either the adjuvant or metastatic setting. This study compared incidence and severity of neuropathy adverse events (AEs) in pts receiving eribulin or IXA. Methods: Pts (locally recurrent/MBC; prior taxane therapy; ≥1 prior chemotherapy for advanced disease; pre-existing neuropathy Grade 0 [n=51] or 1 [n=53]) were randomized to receive 1.4 mg/m2 eribulin mesylate (2–5-min intravenous (IV), Days 1 and 8 of a 21-day cycle) or 40 mg/m2IXA (3 h IV, Day 1 of a 21-day cycle). The primary objective was to compare incidence of neuropathy AEs by CTCAE grade. Secondary objectives: severity of neuropathy AEs by CTCAE grade, patient neurotoxicity questionnaire (PNQ), and vibration sensitivity using Vibration Perception Threshold (VPT); time to onset of treatment-emergent neuropathy (TEN); efficacy; safety and tolerability. Results: Incidences ofPN and TEN (all grades) with eribulin (n=51) versus (vs) IXA (n=50) were 31.3% vs 44.0%, p=0.1632 and 33.3% vs 48.0%, p=0.1284, respectively. Severity (grade ≥3) was numerically lower with eribulin than IXA (PN: 9.8% vs 20.0%; TEN: 9.8% vs 22.0%). No significant differences were seen in baseline to worst PNQ scores. Median worst post-baseline VPT scores were lower with eribulin than IXA (index finger: 2.3 vs 2.4 vibration units [vu]; great toe: 7.75 vs 8.6 vu). Median time to onset of TEN was earlier with IXA (11.6 weeks [wks]) than eribulin (35.9 wks). TEAEs were comparable. Median treatment duration was 15.0 wks (eribulin) and 10.5 wks (IXA). Reasons for discontinuation (eribulin vs IXA): TEN (3.9% vs 18.0%); any TEAE (11.8% vs 32.0%); progressive disease (68.6% vs 48.0%). Objective response and clinical benefit rates were 15.4% vs 5.8% and 26.9% vs 19.2% for eribulin and IXA, respectively. Conclusions: Although not statistically significant, neuropathy AEs were less common with eribulin than IXA. Eribulin was associated with longer time to onset of TEN and fewer discontinuations due to neuropathy and other toxicities.
Feasibility of two schedules of weekly paclitaxel as (neo)adjuvant treatment for patients (PTS) with HER2-negative breast cancer (BC) in the Brazilian community setting.
Authors: Santana Iuri Amorim , De Oliveira Julia Andrade , Amaral Alan Alves , Testa Laura , Landeiro Luciana Garcia , Costa Romulo Leopoldo de Paula , Hajime Marcelo , Ferrari Marcela Simonis Martins , Petry Vanessa , Heinemann Cohn Daniela J. B. , Hoff Paulo M. , Mano Max S. 
Published: February 2017

122 Background: Paclitaxel is one of the most active drugs in BC and the weekly administration has been shown more effective and better. GEICAM9906 was a phase III trial that demonstrated the effectiveness and safety of a pragmatic dose-dense schedule of 100mg/m2 of paclitaxel given over 8 consecutive weeks (w), without G-CSF support. This schedule has been adopted at our institution in 2009 for HER2 negative disease and herein we present the first off-trial experience and also compare its safety profile with that of a historical cohort of pts treated with the conventional 80mg/m2 x12w schedule. Methods: The study consists of a retrospective review of medical files from pts with locally advanced BC treated with (neo)adjuvant paclitaxel-based therapy with one of two schedules: (1) 80 mg/m² x 12w or (2) 100 mg/m² x 8w. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE). Results: We reviewed files from 326 women with a median age of 52 (±10.9). Seventy and 256 pts received schedule (1) and (2), respectively. No significant difference was observed in the incidence of G3/4 toxicity: pneumonitis (2.8% vs 0.3% p=0.097), neuropathy (2.8% vs 0.7% p=0.303); hand-foot syndrome (1.4% vs 0.3% p=0.538); anaemia (0 vs 0.6% p=0.624); neutropenia (5.7% vs 6.2% p=0.408) with only one case of febrile neutropenia in schedule (2) arm; without cases of grade 3/4 thrombocytopenia, nausea, mucositis or anaphylaxis in both groups. Also, no significant difference was seen when comparing all grades toxicty. The dose intensity of paclitaxel was higher in schedule (2) with 97.72 mg/m² per week vs 77.07 mg/m² per week (p<0.0001). Conclusions: Weekly paclitaxel given according to GEICAM9906 is a pragmatic and well tolerated schedule when used in the Brazilian community setting, with a safety profile comparable to the conventional 80mg/m2 x12w schedule. In addition to being convenient to pts, it may also be cost-effective because of a lower number of clinic visits and infusions.
Characterization of the overall survival benefit in ENCORE 301, a randomized, placebo-controlled phase II study of exemestane with and without entinostat in ER+ postmenopausal women with metastatic breast cancer.
Authors: Klein Pamela , McCulloch William , Ordentlich Peter , Cruickshank Scott , Rees Miranda , Yardley Denise Aysel 
Published: February 2017

128 Background: Histone deacetylase inhibitors (HDACi) prevent the emergence of drug tolerant clones and sensitize cells to a variety of anti-cancer therapies. We previously reported ENCORE 301, a randomized placebo controlled phase II study comparing exemestane with (EE) and without (EP) the HDACi entinostat met its primary endpoint of prolonging progression free survival (PFS) (4.3 months vs 2.3 months) and extending overall survival (OS) benefit (26.9 vs 19.8 months). In order to characterize and better understand the OS benefit, exploratory analyses were conducted. Methods: Hazard ratios (HR) for treatment were estimated from the Cox proportional hazards model, with EP serving as the reference treatment in the calculations. Inferential comparisons between treatment groups were made using the log-rank test. Results: Analysis of OS across multiple subsets of interest demonstrated a consistent benefit in EE group versus EP. Sensitivity analysis of baseline characteristics potentially impacting OS did not identify any factors that influenced the effect of EE on OS. Examination of treatments received during follow-up after discontinuation of EE and EP demonstrated balance between treatment group for patients receiving chemotherapy (48% EE: 44% EP), hormone therapy (37% EE: 35% EP), bisphosphonates (2% EE; 0% EP), radiation (6% EE; 5%EP), and surgery (0% EE: 2% EP). Compared to EP, OS was longer in EE group for patients whose first subsequent treatment was a hormone therapy (EE median not reached vs EP median 20.5 months; HR 0.65 [95% CI 0.26, 1.58]) or chemotherapy (EE median 26.9 months vs EP median 17.6 months; HR 0.51 [95% CI 0.25, 1.04]). Updated PFS and OS data will also be presented along with correlation analysis of PFS and OS. Conclusions: Analyses of baseline characteristics, subsequent treatment and subsets of prognostic factors in ENCORE 301 did not identify any contributing factors that account for the extended OS benefit in the EE treatment group. Long lasting effects of entinostat on progenitor cells, emergence of drug tolerant cells and or priming to subsequent therapies cannot be ruled out.
Optimizing breast cancer diagnosis in Kenya: Importance of standardization of technical methodologies for comparative breast cancer data.
Authors: Sayed Shahin , Moloo Zahir , Wasike Ronald , Chauhan Rajendra R. , Vinayak Sudhir , Karanu Joseph , Bird Peter , Njoroge Wambui , Nzioka Ancent , Gachii Andrew , Chumba David , Otieno James Obondi , Mohamed Musa , Al-Ammary Ammar , Sherman Omar , Prasad Satya , Kyobutungi Catherine , Saleh Mansoor N. 
Published: February 2017

139 Background: An analysis of 322 cases referred to Aga Khan University, Nairobi, revealed 56% estrogen receptor (ER) positive tumors and 35% prevalence of triple-negative breast cancer (TNBC). Findings were retrospective and limited by inability to control pre-analytical variables that could potentially impact results. Methods: As part of an ongoing prospective study assessing prevalence of TNBC in the three major ethnic groups in Kenya, we gathered a multidisciplinary team from 10 collaborating health facilities around Kenya for an educational workshop. The objectives were to assess baseline capabilities and pre-analytic variables at each center, identify gaps and provide hands-on training in order to ensure accuracy and validity of ER/PR/HER2 prevalence data gathered as part of the study. Results: See table. Breast cancer biopsies ranged from one to 20 per month per center. Diagnosis was predominantly by FNA and ER/PR/HER2 was not routinely performed. Buffered formalin fixative and standardized CAP reporting format was employed only at one center. A survey 3 months following the workshop demonstrated increase in diagnostic core biopsiesby 90%, and uniform use of buffered formalin fixative, and adoption of synoptic reporting. 66 prospective cases of breast cancer from the 10 institutions with patients from different ethnic backgrounds have been subsequently collected and IHC data will be presented. Conclusions: Much has been made of the difference in prevalence of TNBC in Africa as compared to North America, yet little attention has been paid to differences in diagnostic methodologies and basic tissue handling techniques that can potentially alter results. Despite limitations of resources, educational workshops make it possible to improve the practice of breast cancer diagnosis, and thereby enable accurate comparative analysis between breast cancers in the developing and the developed world. [Table: see text]
Ki-67, p53, and clinical outcomes of patients with triple-negative breast cancer.
Authors: Nishiyama Yasuyuki , Nishimura Reiki , Osako Tomofumi , Okumura Yasuhiro , Arima Nobuyuki 
Published: February 2017

142 Background: Triple-negative breast cancer (TNBC) tends to produce a poor prognosis because of aggressive tumor biology and lack of targeted agents. Breast cancer with a high Ki-67 value responds better to chemotherapy but is associated with lower relapse-free (RFS) and overall survival rates. The basal-like subtype overlaps with TNBC in approximately 70% to 80% of the cases, and the vast majority of basal-like subtypes have mutated p53. The aim of this study was to evaluate the clinical and prognostic significance of Ki-67 and p53 in patients with TNBC. Methods: We retrospectively reviewed 1,711 patients with pT1-3 invasive breast cancer diagnosed between 2001 and 2010. Of the 200 TNBC cases, 165 patients received adjuvant chemotherapy. Cases were classified as luminal (ER+ and/or PR+ and HER2-), HER2 disease (HER2+) and TNBC (ER-, PR- and HER2-) subtypes. Estrogen receptor (ER) and progesterone receptor (PR) positivity was defined as ≥10% positive tumor cells with nuclear staining. Ki-67 was classified into the following three groups: low (<20%), intermediate (20-50%) and high (≥50%), and the p53 high group was indicated by ≥50% staining. RFS was compared according to the level of Ki-67 and p53. Results: Patients with a high Ki-67 value were frequently seen in 53% of the cases with TNBC (luminal: 6% and HER2 disease: 25%, p<0.0001). The greatest proportion of patients in the low p53 group were the luminal type (luminal: 7%, HER2 disease: 49%, TNBC: 54%, p<0.0001). A high Ki-67 value was not associated with poor RFS in TNBC (p=0.2734). A high p53 expression was associated with poor RFS (p=0.024). TNBC with adjuvant chemotherapy and a high p53 expression tended to produce poor RFS (p=0.0516). Conclusions: TNBC with a high Ki-67 value was not associated with poor prognosis in this study. However, p53 status could be a significant prognostic factor in TNBC patients, especially in adjuvant chemotherapy cases.
Evaluation of current consensus panel guidelines for APBI: A pooled analysis of William Beaumont Hospital and American Society of Breast Surgeons MammoSite registry trial data.
Authors: Wilkinson John Ben , Beitsch Peter D. , Arthur Douglas W. , Shah Chirag , Haffty Bruce George , Wazer David E. , Keisch Martin , Shaitelman Simona Flora , Lyden Maureen , Vicini Frank 
Published: February 2017

145 Background: To determine whether the ASTRO Consensus Panel (CP) guidelines for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite Registry Trial. Methods: 2,127 cases of early-stage breast cancer were treated using APBI (WBH: n=678; ASBrS: n=1,449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3D-CRT, n=206) while all Registry Trial patients received balloon-based brachytherapy. Patients with complete coding necessary for ASTRO CP assignment (n=1,813) were divided into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CP group. Results: Median age was 65 years (32-94 years) and median tumor size was 10.0mm (0-45mm). The WBH cohort had more node-positive disease (6.9% vs. 2.6%, p<0.01) and cautionary patients (49.5% vs. 41.8%, p=0.06). Five-year rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%, respectively. When analyzed by CP group, the rate of IBTR was not statistically higher for suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (p=0.20). The non-significant increase in IBTR for grouped cautionary/unsuitable categories was due to increased elsewhere failures/new primaries (p=0.04), not true recurrences (1.1-1.2%, all groups, p=0.94). A higher rate of DM was observed within the cautionary and unsuitable groups (3.3-3.6% vs. 0.7% for suitable, p=0.01), although cause-specific survival was the same for all patient categories (98.0-98.6%, all groups, p=0.47). Conclusions: Excellent outcomes following breast conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CP guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure within the largest patient population of cases treated with APBI to date.
Impact of the number of cautionary/unsuitable risk factors on outcomes following accelerated partial breast irradiation.
Authors: Wilkinson John Ben , Wobb Jessica , Shah Chirag , Fowler Ashley , Mitchell Christina , Wallace Michelle , Grills Inga S. , Stromberg Jannifer S. , Vicini Frank , Chen Peter Y. 
Published: February 2017

146 Background: Current guidelines for APBI stratify appropriateness of treatment outside of a clinical trial. Limited data are available, however, regarding the impact of the number of risk factors (RFs) per patient on clinical outcomes. Methods: 692 patients were treated with APBI at a single institution between 10/1992 and 10/2011. Patients were stratified by the ASTRO guidelines as suitable, cautionary, and unsuitable. Outcomes including ipsilateral/contralateral breast tumor recurrence (IBTR/CBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause specific survival (CSS), and overall survival (OS) were evaluated by risk group and number of RFs. Results: Median follow-up was 5.2 years (range: 0-18.3).Distribution within CP risk-groups was suitable: 240, cautionary: 343, and unsuitable: 109 patients. Increased IBTR (2.0% v. 0.6%, p=0.03), DM (6.5% v. 1.5%, p=0.02), and decreased DFS (92% v. 98%, p=0.01) were noted for patients with 2+ cautionary RFs (n=115) vs. 1 RF (n=228). Those with 2+ unsuitable RFs had higher RR (7.7% v. 1.7%, p=0.05). Pooled analysis revealed increased IBTR/RR for patients with 3+ combined cautionary/unsuitable RFs vs. 2 or fewer combined RFs (Table). Univariate analysis showed increased DM with increasing tumor size/T-stage (p<0.01), ER negativity (p=0.04), LVSI (p=0.01), + LN (p<0.01), and increasing number of RFs (p<0.01). No single RF was associated with an increased risk of local recurrence on UVA. Conclusions: Three or more cautionary or unsuitable APBI RFs is associated with higher local, regional, and distant recurrence. Patients with fewer than 3 total RFs have a 98% locoregional control at 5 years and likely remain good candidates for APBI. Future attempts to risk stratify patients may need to account for the number of RF present in order to appropriately classify patients. [Table: see text]