bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central review of discordant samples for microarray-based ER, PR, and HER2 and local IHC/FISH assessment worldwide from 827 patients.
Authors: Wesseling Jelle , Tinterri Corrado , Sapino Anna , Zanconati Fabrizio , Lutke Holzik Martijn , Nguyen Bichlien , Deck Kenneth B. , Querzoli Patrizia , Perin Tiziana , Giardina C , Seitz Gerhard , Guinebretiere Jean-Marc , Barone Julie , Watanabe Toru , De Snoo Femke , Stork-Sloots Lisette , Cusumano Pino 
Published: February 2017

11 Background: Differences in fixation and IHC and subjective interpretation can substantially affect the accuracy and reproducibility of estrogen receptor (ER), progesterone receptor (PR) and HER2 expression. The commercially available TargetPrint test measures the mRNA expression level of ER, PR and HER2 and is 98% concordant with centrally assessed ER as presented by Viale et al, SABCS 2011. This study compares results from the microarray-based TargetPrint with IHC and FISH (for HER2 IHC2+) generated by local standard procedures. Methods: Fresh tumor samples (core needle biopsies or surgical) were collected for 831 patients diagnosed with breast cancer stage I to IV (Feb 2008 - Jan 2011) from 22 hospitals from Europe, New Zealand, Japan and US. The results of the IHC/FISH assessments performed according to the local standards at the hospitals were compared to the quantitative gene expression readouts with TargetPrint. Discordant cases were centrally reviewed for IHC/FISH assessment. Results: Of the 831 samples, IHC assessment was unknown for 4 ER/ PR samples; HER2 was unknown for 12 samples. Comparison of IHC and gene expression read out by TargetPrint showed a concordance of 95% for ER; 83% for PR and 94% for HER2. In this study, 3% of all IHC ER positive samples were classified negative by microarray, and 11% of IHC PR positive samples were classified negative by microarray. For HER2, 4% of IHC/FISH HER2 positive samples were classified negative by microarray and 2% of IHC/FISH HER2 negative samples were classified positive by microarray. Most notably, all available 5 ER IHC negative/TargetPrint positive samples turned out to be positive with central re-assessment. HER2 IHC2+ samples with discordant classifications for TargetPrint and local assessment are currently being reviewed for FISH/SISH assessment. Conclusions: Microarray based readout of ER, PR and HER2 status using TargetPrint is fairly comparable to local IHC and FISH analysis in 827 analyzed samples in various hospitals worldwide. However, re-assessment of discordant cases–especially IHC ER-/TargetPrint ER+ cases- confirms TargetPrint to be a useful high quality second opinion for local IHC/FISH assessment.
Interim safety results of eribulin (E) combined with ramucirumab (RAM) in patients (pts) with advanced metastatic breast cancer (MBC).
Authors: Yardley Denise Aysel , Osborne Cynthia R. C. , Richards Paul D. , Daniel Brooke R. , Danso Michael A. , Favret Anne , Bromund Jane , Hsu Yanzhi , Ibrahim Ayman B. 
Published: February 2017

110 Background: VEGF-mediated angiogenesis contributes to breast cancer (BC) pathogenesis. RAM (IMC-1121B), a fully human IgG1 monoclonal antibody (MAb), targets VEGFR-2, blocking the interaction of VEGF ligands and VEGFR‑2. DC101 (murine anti-VEGFR-2 MAb) impairs vascular function and increases tumor hypoxia in xenograft BC models and inhibits tumor growth in cytotoxic-resistant models. E is a novel non-taxane microtubule inhibitor indicated in MBC pts who have received ≥2 prior chemotherapy regimens, including an anthracycline and a taxane. It is hypothesized that addition of RAM to E as 3rd-5th line therapy in MBC will result in an improvement of median PFS in this ongoing, multicenter, US study. A planned safety analysis of an initial cohort is reported. Methods: Pts with locally recurrent or MBC (HER2+ or HER2-) and 2-4 prior chemotherapy regimens are randomized 1:1 to receive RAM+E or E (E 1.4 mg/m2 Days 1, 8; RAM 10 mg/kg Day 1; q21 days). Pts are stratified by TNBC and prior antiangiogenic therapy status and must have ECOG PS 0-1 and normal LVEF. Planned accrual: 134 pts. Results: Evaluable pts (n=13, 8 RAM+E) received ≥1 dose of RAM+E or E and completed 2 cycles of therapy (or discontinued prior to completing the initial 2 cycles). Median age is 55 yrs. Assessment of adverse events (all cause) revealed nausea, fatigue, headache, and neutropenia were more frequent for RAM+E; anemia was more frequent for E. G1 sensory neuropathy was reported for 1 pt in each arm. One RAM+E pt experienced G3 febrile neutropenia and odynophagia, recovered within a week, and subsequently received reduced dosage (E = 1.1 mg/m2; RAM = 8 mg/kg). No deaths are reported. The safety assessment committee recommended to continue the trial unmodified. Conclusions: Based on preliminary data, the combination of RAM+E demonstrates an acceptable toxicity profile. Accrual continues, with planned updated safety and dose intensity data to be presented at the meeting. [Table: see text]
Acute side effects of intraoperative electron radiotherapy of breast cancer.
Authors: Boelke Edwin , Budach Wilfried , Janni Wolfgang , Zwiefel Karin , Njanang Freddy-Joel , Simiantonakis Ioannis , Matuschek Christiane 
Published: February 2017

112 Background: Intraoperative boost irradiation as part of breast-conserving therapy is a perfect method to adequately capture the high risk tumor relapse area. The most homogeneous dose distribution is achieved with electrons. Intraoperative radiotherapy (IOERT) as a boost for breast cancer releases a high single dose of radiation to the breast tissue; therefore acute toxicity is of particular attention. To date there is only inadequate information available on breast cancer patients treated with IORT using electrons applied as a boost. We therefore analyzed the acute toxicity after radiotherapy with 10 Gy as a boost with a minimum follow-up of 3 months. Methods: A total of 69 patients treated with IOERT (10Gy with 5, 7 and 9 MeV electrons) with a dedicated robotic linac (NOVAC 7, New Radiant Technology, Aprilia, Italy) to the tumor bed during breast-conserving surgery as a boost followed by whole-breast radiotherapy (WBRT, 50.4 Gy; 1.8 Gy per fraction) were included in this study. All patients underwent a retrospective follow-up (median, 8 months; range 1-17 months) regarding acute side effects within the first three months. Toxicities were documented using the common toxicity criteria (CTC 4.0 of the European Organization for Research and Treatment of Cancer). Results: The IOERT was well tolerated. As a side effect there was one patient with seroma. Two patients developed chronic pain in the irradiated breast. Two patients developed a secondary wound healing. The remaining patients did not develop any grade 3 or 4 side effects. The observed toxicity rates were not influenced by age, tubus size, electron energy or systemic therapy. Conclusions: After IOERT of the breast using electrons we did not find any unexpected acute toxicity rates.
PIK3CA as a predictor of the clinical efficacy for epirubicin plus docetaxel neoadjuvant chemotherapy in breast cancer.
Authors: Li Xi Ru , Zhang Yan Jun , Liu Mei , Zheng Yi Qiong , Yang Hui Yi 
Published: February 2017

113 Background: PIK3CAgene mutations are the most common activating mutations in human breast cancer (BC). Its association with the resistance to herceptin in HER2-positive BC was reported, but whether it’s related to the efficacy of neoadjuvant chemotherapy is unknown. Methods: We reviewed records of 108 patients with BC treated with epirubicin plus docetaxel neoadjuvant chemotherapy between June 2005 and April 2011. 92 patients’ clinical and pathologic objective response data were collected. FFPE tumor biopsies obtained at the time of diagnoses (and before treatment) were collected. EGFR, KRAS, BRAF, PIK3CA mutations and HER2, PTEN, EGFR mRNA expression were analyzed by liquidchip technology. Chi-square test and Fisher’s exact test were used in statistical analysis. A p value less than 0.05 was considered statistically significant. Results: No mutation was detected in EGFR, KRAS and BRAF. The mutation rate of PIK3CA was 35.1% (38/108), and mutation rates of E542K, E545K, H1047L and H1047R were 3.7, 10.2, 3.7 and 17.6% respectively. More PIK3CA mutations were detected in HER2 high expression tumors (p=0.018). No correlation was found between PIK3CA mutations and PTEN, EGFR expression. Clinical response (CR+PR, 63/92) was associated with PIK3CA mutations (p=0.002). However, PIK3CA mutations rate between pathologic complete release (pCR, 7/92) and non-pCR group was not significantly different (p=0.422). Conclusions: PIK3CA mutation may predict better clinical response in BC patients treated with epirubicin plus docetaxel neoadjuvant chemotherapy. More studies are needed to validate these results and the correlation between PIK3CA mutations and pCR.
Barriers to mammography among underserved women in a breast health center outreach program.
Authors: Fayanju Oluwadamilola M. , Kraenzle Susan , Drake Bettina F. , Si Xuemei , Oka Masayoshi , Goodman Melody S. 
Published: February 2017

13 Background: An outreach registry of Breast Health Center patients was developed in 2006 to evaluate the effectiveness of mobile mammography among the medically underserved. Registry included collection of medical record data, demographic data, and answers to a questionnaire about perceptions of breast cancer screening. Here, we examine barriers to mammography. Methods: Between April 2006 and May 2011, 9,082 women were registered. Data from registrants’ first screening visit (n= 8,916) were analyzed using multivariable logistic regression examining three outcomes identified as barriers to mammography: cost, fear of pain during the procedure, and fear of receiving bad news. Two-tailed p<0.05 was considered significant. Results: The majority of registrants were black (54%), uninsured (74%), screened on a van (83%), resided in the greater St. Louis region (84%), had an annual income <$20,000 (87%), and reported a good or excellent experience as part of the outreach program (92%). Fears of cost, mammogram-related pain, and bad news were reported by 40%, 13%, and 13% of registrants, respectively. Regression analyses revealed that being employed (odds ratio [OR] 1.109, p=0.0323) and living in the Bootheel of Missouri (OR 2.319, p<0.0001) were associated with a higher likelihood of perceiving cost as a barrier to mammography, while those who had insurance (OR 0.439) and were Hispanic (compared to non-Hispanic [NH] whites [OR 0.338]) were less likely to report cost as a barrier (both p<0.0001). Registrants who were screened on the van (OR 1.633), had insurance (OR 1.391), and were NH black (OR 1.324) were more likely to report fear of procedural pain as a barrier (all p<0.0001). Having insurance (OR 1.378), being NH black (OR 2.458), and being Hispanic (OR 2.980) were associated with reporting fear of receiving bad news as a barrier (all p>0.0001), while older women (OR 0.985, p=0.0001) and women who were screened on the van (OR 0.772, p=0.0026) were less likely to report this concern. Conclusions: Despite provision of free services, cost, fear of procedural pain, and fear of abnormal results remain barriers to mammography utilization among medically underserved women, suggesting the need for more breast health education in this population.
Neoadjuvant therapy (NAT) for breast cancer at the Odette Cancer Centre: What have we been doing and how do we compare?
Authors: Arce Claudia , Gandhi Sonal 
Published: February 2017

131 Background: NAT is standard of care for locally advanced breast cancer (LABC). Early breast cancer (EBC) may also benefit, particularly certain subtypes, such as HER2-enriched or basal- like. We developed a clinical care pathway to standardize the assessment and treatment of LABC and higher-risk EBC at the Odette Cancer Centre (OCC). Purpose: Evaluate treatment patterns within the LABC/NAT program at the OCC, and to determine if these patterns changed after the introduction of a clinical care pathway. This study also aimed to evaluate treatment efficacy (pCR rates) by NAT regimen and breast cancer phenotype, as compared to the literature. Methods: Retrospective chart review of patients treated with NAT at the OCC from January 2008 to March 2012. Results: 158 patients were reviewed. Median age at diagnosis was 50 years (28-85), and median tumor size was 7 cm (0-21). 74% were stage IIB-IIIB, and 11.2% were considered non-LABC (or EBC). 65.8% of breast cancers were estrogen receptor positive (ER+), and 29.7% were HER-2 positive (HER2+). 96% of NAT chemotherapy regimens were anthracycline and taxane-based, and trastuzumab was given to 29.7% of HER-2 positive cases. pCR was achieved in 20.9% of all cases and this did not vary by type of chemotherapy regimen; pCR rates did vary by breast cancer phenotype, with 6.25%, 57.5% and 25% pCR achieved for ER+, HER2+ and triple negative (TN) cancers, respectively. Median follow-up was 13 months (0-46), and overall DFS was 90%; survival did not vary by NAT regimen or pCR, but did vary by phenotype, whereby DFS was 100% for HER-2 positive, 90% for ER+, and 78% for TN cancers. There was no significant difference found in types of patients, NAT regimen, or pCR rates before and after the pathway was introduced. Conclusions: Practice patterns at the OCC in NAT for breast cancer remained unchanged before and after development of a clinical care pathway, which was meant to standardize the approach to and to possibly increase the use of NAT from beyond LABC to higher-risk EBC. This is likely due to limited pathway dissemination, but other factors contributing to this should be evaluated. pCR rates by cancer phenotype were similar to those found in the literature.
Thymidylate synthase expression as a predictive factor for response and progression-free survival in metastatic breast cancer patients.
Authors: Seki Hirohito , Jinno Hiromitsu , Hayashida Tetsu , Takahashi Maiko , Kaneda Munehisa , Suzuki Keiichi , Hara Hidenori , Osaku Masayoshi , Yamada Yoshinori , Asamuna Humiki , Kitagawa Yuko 
Published: February 2017

132 Background: S-1, an oral fluoropyrimidine formulation that combines tegafur, 5-chloro-2,4-dihydroxypryidine, and potassium oxonate in a molar ratio of 1:0.4:1 has been widely used against solid cancers including gastric, colorectal, pancreatic, lung and breast cancer. In a phase II study, the response rate (RR) was 41.7% and the median survival was 872 days among taxane-pretreated patients with metastatic breast cancer (MBC). However, the predictive factor of S-1 in patients with MBC has not been determined yet. The purpose of this study is to investigate the correlation between 5-FU-related enzyme and clinical efficacy of S-1 in patients with MBC. Methods: Forty-eight patients with MBC were treated with S-1 twice daily at a dose of 80 mg/m2 for 4 weeks, followed by a 2-week rest interval. Laser-captured microdissection was performed from the formalin-fixed, paraffin-embedded tumor sections at surgery and the expression of 5-FU-related enzyme including thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) was evaluated by RT-PCR. Results: The median age was 58 years. ER, PgR, HER2 was positive in 57, 28, and 14% of the entire patients, respectively. The median number of pretreated chemotherapy regimens was 2 (range 0-6). The sites of metastatic disease were the viceral in 25 patients, bone in 9 patients and soft tissue in 17 patients. The overall response rate (RR) was 22.9% (11/48) and clinical benefit rate was 41.7% (20/48). The median time to tumor progresssion (TTP) was 14.3 months (range 6.0 – 22.7). ER, PgR and HER2 status was not significantly correlated with RR. TS expression was significantly associated with clinical efficacy of S-1. Moreover, it is notable that triple negative breast cancer (TNBC) revealed lower TS expression than luminal type (TNBC vs luminal type = 80% (8/10) vs 36.4% (4/11), P= 0.054, OR 0.143, 95% CI 0.020-1.032). According to the correlation between metastatic sites and RR, better RR was noted for soft tissue metastases (soft tissue vs visceral = 25% (5/20) vs 84% (5/6), OR 15.0 (95%CI 1.40–161.05). Conclusions: This study demonstrated that TS is a significant predicitve factor of S-1 in patients with MBC.
Long-term outcome from RTOG 9517: A phase I/II study of accelerated partial breast irradiation (APBI) with mulitcatheter brachytherapy (MCT) following lumpectomy for early-stage breast cancer.
Authors: White Julia R. , Winter Kathryn A. , Kuske Robert R. , Bolton John S. , Arthur Douglas W. , Scroggins Troy , Rabinovitch Rachel , Kelly Tracy R. , Toonkel Leonard M. , Vicini Frank A. , McCormick Beryl 
Published: February 2017

147 Background: Comparison of APBI to whole breast irradiation post lumpectomy for breast conservation is ongoing in phase III trials. However, APBI has gained acceptance in clinical practice despite relatively limited long-term data. RTOG 9517 studied MCT, one of the earliest methods of APBI, and can uniquely provide long-term cancer outcomes. Methods: Eligibility was stage I/II unifocal breast cancer <3cm, invasive non-lobular histology without EIC, negative surgical margins, and 0-3 positive axillary nodes; no extracapsular extension. The target volume was the lumpectomy cavity plus a 2 cm radial and 1 cm ant/post margin. Low Dose Rate (LDR), 45 Gy in 3.5-5 day, or High Dose Rate (HDR) 34 Gy in 10 BID fractions over 5 days was delivered. A rapid dosimetry review was done to assure dose delivery per protocol. Systemic therapy was per physician’s discretion. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on ipsilateral breast failure (IBF), contralateral breast cancer events (CBE), regional (RF) and distant failure (DF) (cumulative incidence) disease-free (DFS), relapse-free (RFS), and overall survival (OS), (Kaplan-Meier). Results: The median follow up is 12.1 years (yr). 100 patients were accrued from 1997-2000; 98 were evaluable; 65 HDR and 33 LDR MCT. Median age was 62; 88% had T1 tumors; 12% T2; 81% p N0, 19% pN1; 77% ER and/or PR +; 19% ER - and PR -; 33 % received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 6 IBF for a 10 yr rate of 6.2%; 2 IBF were outside the APBI field. There were 5 total RF for a 10 yr rate of 5.2%, respectively. There have been 5 CBE for a 10 yr rate of 4.2%. Failure patterns were: 4 isolated IBF, 1 isolated RF, 8 DF only, 1 IBF+RF, 1 IBF+RF+DF, 1 RF+CBE, 1 RF+DF, 3 CBE, and 1 CBE+DF (21 total failures). Eleven patients have developed DF; 8 have died of breast cancer, 22 have died from other causes. The 10 yr DFS, RFS and OS are 69.8%, 71.9%, and 78.0%, respectively. Conclusions: This multi-institutional phase II trial studying MCT-APBI continues to report durable local regional cancer control rates with long term follow-up. Supported by NCI U10 grants CA21661 and CA37422.
Trade-offs associated with axillary lymph node dissection: Implications of the eligibility versus enrollment in ACOSOG Z0011.
Authors: Krishnan Monica Shalini , Recht Abram , Bellon Jennifer Ruth , Punglia Rinaa Sujata 
Published: February 2017

151 Background: Results from ACOSOG Z0011 suggest that axillary lymph node dissection (ALND) may not be necessary for patients following positive sentinel lymph node biopsy (SLNB). Concerns have been raised regarding the generalizability of this trial, given the low-risk patient population. It is uncertain whether a subgroup who would have been eligible for ACOSOG Z0011 but were not adequately represented in the study may still benefit from ALND. Methods: We constructed a decision analysis using a Monte Carlo model to simulate axillary recurrence (ALR) risk, lymphedema, and quality of life of women age 45, 55, and 75 y/o with stage II cancers following breast conserving surgery (BCS) with positive SLNB who were then treated with either ALND and whole-breast radiation (BRT) or BRT alone. Women were divided into two risk groups: those with a risk of residual nodal involvement of 30-60% (high risk); and those with a risk less than 30% (low risk, similar to the Z0011 patients). Probabilities and utilities for health states were derived from previous studies. Results: BRT alone resulted in improved quality-adjusted life expectancy (QALE) in the low-risk group, while ALND with BRT resulted in improved QALE in the high-risk group. Overall survival (OS) was similar at 5 years with both treatment strategies in both groups but was superior with ALND at 20 years in the high risk group (Table). Differences in outcomes decreased with increasing age. In the low-risk group, sensitivity analysis showed BRT alone is preferred unless the ALR risk with BRT is greater than 1.6% or the lymphedema risk with ALND is less than 10%. In the high-risk group, ALND with BRT is the preferred strategy unless the ALR risk with BRT is less than 2.3%. Conclusions: Patients who would have been eligible for ACOSOG Z0011 but are at higher risk of having residual nodal disease following BCS and positive SLNB may benefit from ALND plus BRT rather than BRT alone. [Table: see text]
Surgical techniques, biomaterials, and patient variables that impact peri-operative nipple necrosis in nipple-sparing mastectomy.
Authors: Gould Daniel J. , Hunt Kelly , Liu Jun , Kuerer Henry Mark , Crosby Melissa , Kronowitz Steven J. 
Published: February 2017

152 Background: Nipple sparing mastectomy is for treatment of early stage breast cancer and risk reduction in patients at high risk for breast cancer. A high rate of nipple loss after NSM (10% to 30%) has slowed incorporation of NSM into clinical practice. No study has evaluated whether clinical and technical factors contribute to nipple loss by decreasing blood supply to the nipple areola complex (NAC). The objective here was to determine the impact of patient variables and surgical factors on survival of the nipple following NSM and to compare rates of complications of NSM to those of SSM. Methods: We evaluated 233 cases of immediate breast reconstruction following mastectomy at MD Anderson Cancer Center between September 2003 and May 2011. 113 NSM procedures were randomly matched to 120 SSMs based on stage, comorbidities, and age. The NSM group was analyzed for variables that correlated with partial or total nipple loss. Results: In the NSM group, the complication rate was 28%, compared to 27% in SSM (p > 0.99). The nipple loss rate in NSM was 20%. In SSM, axillary node dissection increased complications compared to sentinel lymph node biopsy (p = 0.01). Body mass index, breast ptosis, breast cancer pathology, distance of the lesion to the NAC and use of neoadjuvant chemo or radiation therapy had no effect on nipple loss. Vascular comorbidities and smoking lead to increased nipple loss, with borderline p values (p = 0.09 and p = 0.08, respectively). When compared to A- and B-cup breasts, larger breasts had higher nipple loss (6% and 34%, respectively; p=0.003). Surgical incision location did not affect nipple loss, neither did number of prior NSM procedures performed by the breast surgeon (p = 0.86). Axillary lymphadenectomy (p = 0.13), separate axillary incision (p = 0.25), type of breast reconstruction (p = 0.23), and application of bioprosthetic sling (p = 0.27) may have impacted nipple loss if a larger sample size was studied. Conclusions: Patient variables and surgical technique can alter the rate of nipple loss with NSM. This study helps to define patient populations that may be at risk for necrosis and informs surgeon’s as to the best techniques for reconstruction to decrease the occurrence of nipple loss.