bluuebunny/crossref_metadata_2025_split huggingface dataset:
Periareolar zigzag incision in breast conserving surgery.
Authors: Ko Beom Seok , Kim hee Jeong , Kim Jisun , Lee Sae Byul , Lee jong Won , Sohn Byung Ho , Kim Sung-Bae , Ahn Sei-Hyun 
Published: September 2018

e12093 Background: Breast conserving surgery (BCS) followed by radiation therapy is today standard therapy for early breast cancer. Avoiding scars on the breast is women’s desire. Numerous minimal approaches have evolved due to this concern. The periareolar incision is often used to remove relatively small tumors located near the nipple. But periareolar incision has a disadvantages include limited exposure of the surgical field. Periareolar zigzag incision has the advantage of not only good surgical field but also contributed to better surgical scars. The purpose of this study was to evaluate the usefulness of periaroar zigzag incision and oncological safety. Methods: We retrospectively reviewed breast cancer patients who performed breast conserving surgery with periareolar zigzag incision by one surgeon from January 2016 to December 2016. In this study, patients with bilateral breast cancer or other diseases who underwent cooperative surgery were excluded. Intraoperative frozen section margin was evaluated in all patients and additional resection was performed when positive margin was present. Final margin status was determined by examination of the permanent paraffin-embedded sections. Patients characteristics, tumor characteristics, operative time, size of specimen and the distance from the tumor to nipple were evaluated. Results: A total of 193 patients were reviewed. The median age of the patients was 50 years (range: 25-79 years), median tumor size was 1.7 cm (range: 0-8.8 cm), median tumor distance from the nipple was 3.0 cm (range: 0.5-8.0 cm) and median specimen sized was 5.0 cm (range: 2.0-15.0 cm). The median operation time was 70 minutes (range: 32-138 min) in patients without axillary dissection, and 91 minutes (range: 60-171 min) in patients who underwent axillary dissection. In 13 patients (6.7%), tumor was found in intraoperative frozen biopsy and re-excision was performed. There were no major complications associated with surgery. There were no reoperations due to bleeding or other reasons. Conclusions: In breast conservation surgery, the periareolar zigzag incision technique has good cosmetic effect and a enough operative field can be obtained, so it may be applied oncological safely even when relatively large tumors are removed.
Phase II study on radiofrequency ablation in stage 0 and I breast cancer without extensive intraductal components.
Authors: Imoto Shigeru , Nagamine Shinji , Ito Toshikazu , Tsuda Hitoshi , Tozaki Mitsuhiro , Morita Satoshi , Ueno Takayuki 
Published: September 2018

e12094 Background: We reported about a multi-center registration study on radiofrequency ablation (RFA) in early breast cancer (BC) (ASCO2012 #1119). Although various devices and ablation procedure were used, 5-year’s recurrence-free survival was 96% in 425 cases of T1BC treated with RFA alone. To validate complete pathological ablation in BC, we started a non-randomized phase II study in 2013 (UMIN000013836). Methods: Unilateral BC patients with stage 0 (TisN0M0) or I (T1N0M0 or T1N1miM0) were eligible. Tumor diameter of 2cm or less should be diagnosed by ultrasound and MR mammography. RFA was performed by Cool-tip RF ablation system (Covidien, USA). One month later, ablated tissue was collected by core needle biopsy or vacuum-assisted breast biopsy. Cell viability was determined by central review of independent pathologists using tumor specimens stained with hematoxylin–eosin and nicotinamide adenine dinucleotide (NADH) diaphorase. In case of complete ablation, breast irradiation and adjuvant therapy was planned. In case of incomplete ablation, partial mastectomy was recommended. The primary endpoint is complete ablation rate. The secondary endpoints are breast deformity after RFA, relapse-free survival and overall survival for 10 years. Two-step design consisting of 9 cases at 1st step and 20 cases at 2nd step was used for statistical evaluation. We expected complete ablation rate of 95% and 29 cases were needed to reject the null hypothesis that complete ablation rate would be less than 80% at lower threshold. Thus, 32 cases were required. Results: Thirty-six patients were enrolled between February 2013 and May 2016. The mean tumor size was 1.3 cm measured by MR mammography. Two patients were ineligible because of macrometastasis in a sentinel node. Of 34 eligible patients, one patient had viable cancer cells with NADH diaphorase staining in ablated specimens. Finally, complete ablation rate was 97%. As of January 2017, one patient, who refused adjuvant therapy and breast irradiation, had in-breast tumor recurrence adjacent to previously ablated lesion. Conclusions: Long-term follow-up should be needed, but RFA in early BC is a promising strategy instead of breast-conserving surgery. Clinical trial information: UMIN000013836.
Survival length differences in non-metastatic breast cancer patients with different chemo-radiation time intervals.
Authors: Al-Ward Ruaa , Al Shweiat Wajdi , Lakshmi Talasila , Grewal Sandeep Singh , Subbaiah Perla , Singla Smit , Smith Susan , Kakarala Radhika 
Published: September 2018

e12096 Background: Chemotherapy-radiotherapy time intervals (CRTI) in breast cancer vary based on recovery from chemotherapy side effects and preferences of physicians and patients. Our study aimed to determine the association of the time-interval between chemotherapy and radiation with prognosis (recurrence and survival duration) in non-metastatic breast cancer patients (stages I-III). Methods: We included female patients from Karmanos Cancer Center (KCC) database > 21 years, diagnosed with non-metastatic breast cancer from 2005-2015, who underwent surgery, chemotherapy and radiation. CRTI was divided into <24, 24-30 and >30 weeks. Cox regression analysis using age, race, stage, grade, ER/PR status and CRTI variables was done to determine the independent predictors of prognosis. Kaplan-Meier survival curves were used to demonstrate differences in survival time of CRTI groups. Results: We included 553 patients, majority were Caucasian (460 [83.5%]) with a mean age of 57.0 years (SD 11.9). Patients in the >30 weeks CRTI group were more likely to have stage III breast carcinoma when compared to <24 and 24-30 weeks groups (45.0% vs.12.4% vs. 27.8%, p-value <0.001). There were no significant differences in the local and distant recurrence rates among the 3 groups. Patients in <24 weeks CRTI group had a greater mean survival (118.7 vs. 109.2 vs.100.9 months; p-value 0.016) when compared to 24-30 and >30 weeks groups. Only clinical stage (stage 3 vs. 1 HR 3.60; 95% CI 1.89-7.02) and ER/PR status (negative vs. positive HR 1.74; 95% CI 1.02-2.94) were independent predictors of overall survival in multivariate analysis. CRTI was not significantly associated with survival in multivariate analysis (<24 weeks ref, 24-30 weeks HR 1.09; 95% CI 0.59-1.93, >30 weeks HR 1.48; 95% CI 0.82-2.59). However, patients in >30 weeks group were at greater risk of dying when compared to <24 weeks, even after controlling for stage. Conclusions: Our study showed a trend towards a worse outcome in patients with longer chemo-radiation interval, despite controlling for other variables in the multivariate analysis. The conclusions of this single center study need to be verified by further studies with larger sample size.
Survival prognostic value of obesity in localized triple negative breast cancer in Peruvian women.
Authors: De la Cruz Ku Gabriel Antonio , Enriquez Daniel , Morante Zaida , Eyzaguirre Eduardo , Luque Renato , Fernandez Margiory , Neciosup Silvia P. , Gomez Henry Leonidas 
Published: September 2018

e12100 Background: Obesity has been associated with development of TNBC, but its prognostic value on outcomes is still controversial. The aim of this study was to describe clinicopathological characteristics and compare Disease Free Survival (DFS) and Overall Survival (OS) according to obesity status. Methods: We performed a retrospective study on 1415 patients diagnosed with TNBC, admitted during the 2000-2014 period at the Instituto Nacional de Enfermedades Neoplasicas. We divided TNBC patients in two groups based on WHO classification: Non-obese (BMI: 18.5-29.9) and Obese women (BMI≥30). The survival differences were assessed with log-rank test and prognostic factors were then investigated by Cox regression analysis. Results: The median age was 49.5years (19-89years). Of all registered patients, 389 (27.5%) had obesity and 45% were premenopausal, however obese women were predominantly postmenopausal (55%, p < 0.001). Breast-ovarian cancer family background was present in 16.9%. T3-T4 tumors were 46.1% while 58.8% had nodal involvement. Neoadjuvant treatment was administered to more than a third patients (37.2%), and 430 out of 1415 had conservative surgery. With a median of follow-up of 5.1 years, there were 274 (18.9%) local and 402 (27.8%) distant recurrences registered without differences between groups. In obese women, 5-year DFS was 63%, while non-obese was 65% (HR: 1.10, 95%CI: 0.96-1.4, p = 0.35). 5-year OS, was 65 and 64% in obese and non-obese, respectively (HR: 0.93, 95%CI: 0.8-1.1, p = 0.43). Nevertheless, no significant impact was reached on outcomes at uni or multivariate analysis. In multivariate cox regression analysis, neoadjuvant chemotherapy was related to a better prognosis in DFS and OS; in addition, conservative surgery was a protector factor of OS. On the other hand, T4 and nodal involvement were statistically significant to worse DFS and OS; besides premenopausal status and family background affected the DFS and OS, respectively. Conclusions: In this population of TNBC patients, we did not find negative prognostic impact of obesity in terms of DFS and OS. Others potential factors are needed to be explored in futures studies.
Improving the effectiveness of neoadjuvant chemotherapy in patients with breast cancer with positive estrogen receptor (HR) and HER2 negative.
Authors: Morales Serafin , Gasol Cudós Ariadna , Cordoba Ortega Juan Felipe , Panades Siurana Maria Jose , Vilardell Felip , Iglesias Edelmiro , Salud Salvia Antonieta 
Published: September 2018

e12120 Background: The effect of pathologic complete response (pCR) after neoadjuvant chemotherapy is considered independent of the breast cancer subtype, but the pCR rate in HR positive/HER2 negative patients is smaller than other subtype so it is interpreted as pCR is not being prognostic in luminal breast cancer. In large series residual cancer burden (RCB) assessed by Symmans methods is prognostic in luminal patients if RCB-0 and RCB-I are combined. Methods: 166 patients (March 2000-august 2016) with neoadjuvant chemotherapy based treatment were retrospectively analysed in order to find if common clinicopathological factors could select patients with significative better response considered as pCR or RCB type 0 and I. Results: Median age was 53 years (29-82), median tumor size of 41 mm and 54% of tumors had initial nodal involvement. All patients were estrogen positive and 45% progesterone receptor negative with a median of ki67 expression of 32%. A total of 10% pCR rate was found and the response type RCB 0 and 1 according to Symmans method was 22%. In the univariate model we found and association with pCR and: progesterone receptor negative (p=0.017; OR 4,3), initial tumor size (p=0.026; OR 0,95) and Ki67 index > 30% (p=0.009; OR 5.3). An association with progesterona receptor negative (p=0.008; OR 3,1) was found with the the RCB type 0 and I response. Conclusions: Factors related to better response to neaodjuvant chemotherapy are progesterone receptor negative and level of Ki67 index. Considering this parameters we could found a high rate of response with 24% of pCR and 35% of RGB type 0 and I being the best rate of response in luminal patients.
Effect of neoadjuvant chemotherapy on immune checkpoint expression in breast cancer.
Authors: Stiff Andrew , McQuinn Christopher , Wesolowski Robert , Lustberg Maryam B. , Reinbolt Raquel E. , VanDeusen Jeffrey Bryan , Sardesai Sagar D. , Williams Nicole Olivia , Noonan Anne M. , Dewani Shabana Jaynul , Ramaswamy Bhuvaneswari , Carson William Edgar 
Published: September 2018

e12126 Background: Even with neo-adjuvant chemotherapy (NAC) many breast cancer (BC) patients (pts) relapse, especially triple negative pts. The incorporation of checkpoint inhibitors into NAC for BC is being tested in clinical trials. How NAC affects checkpoint receptor expression is not known. Such information could aid in the rational selection of checkpoints to target during NAC. We sought to characterize changes in the frequency of circulating CD4 and CD8 T cells expressing PD1, CTLA4, LAG3, TIM3, and OX40 over the course of NAC. Methods: In this prospective trial, expression of PD-1, CTLA-4, Lag3, Tim3 and Ox40 on circulating CD4 and CD8 T cells were measured by FACS analysis in pts with operable breast cancer (BC) prior and at the end of NAC. The primary objective was to explore the association between NAC and expression levels of the immune checkpoints. Results: 1, 20 and 3 pts had clinical stage I, II, IIIA, respectively. Median age was 48. 11, 6 and 7 pts were triple negative (TN), HER2+ and hormone receptor (HR)+, respectively. Complete pathologic response rate was 45.8%. Globally CD4 T cells expressing CTLA4, Lag3, Ox40 and PD1 decreased following NAC (all p < 0.01). Conversely, CD8 T cells expressing CTLA4, Lag3 and Ox40 significantly increased (all p < 0.01). More CD8 T cells from HER2+ pts expressed Lag3 prior to therapy compared to HR+ pts (p < 0.05) with a similar trend compared to TN pts. Prior to therapy more CD8 T cells from HER2+ and TN pts expressed Tim3 compared to HR+ pts (p < 0.05 for each). Post therapy more CD4 T cells from HER2+ pts expressed PD1 compared to HR+ and TN pts (p = 0.027 and 0.018 respectively). Clinical response did not predict change in checkpoint expression. An interaction analysis revealed that HER2+ disease predicted a drop in CTLA4 CD4 T cells and a drop in Lag3 CD4 and CD8 T cells over NAC (p < 0.05). Conclusions: This analysis identified changes in checkpoint receptor expression by CD4 and CD8 T cells in BC pts after NAC. Differences in checkpoint receptor expression were found between BC subgroups. This data provides a starting point for understanding checkpoint receptor expression changes with NAC, and could help guide the selection and timing of incorporating checkpoint inhibitors in BC.
Trastuzumab (T) detection in serum using signal amplification strategy for non-faradaic impedimetric sensing quartz crystal microbalance (QCM) based on peptide piezo-immunosensors and its role in breast cancer treatment.
Authors: Chisti Mohammad Muhsin , Liu Juan , Klamerus Justin Frank Antoni , Jaiyesimi Ishmael A. , Batool Syeda Hina , Zeng Xiangqun 
Published: September 2018

e12502 Background: Her2Neu (H) antigen, expressed on 20% of Breast cancers, is an established target for antibody therapy with T. Immunohistochemistry is still the most widely used technique to detect h level which is time consuming and does not reveal any details of interaction between the molecules. We have developed a new innovative biosensor based novel technique to study real time interaction of h antigens with T using QCM Piezo-immunosensor. This quantitative label free peptide based assay can be used to characterize cell surface antigen, to study antigen- antibody interactions and obtain understanding of mechanisms of resistance. Methods: A label free and reagent free peptide mimotope capacitive biosensor is developed for T quantification based on non-Faradaic readout. The low sensitivity issue of capacitive biosensor was overcome with two innovations: peptide mimotope mixed SAM biointerface and dilution of the testing buffer. Signal amplification was achieved through dilution of the PBS buffer to tune Cdl to dominate the overall capacitance change upon target binding. After 1000 times dilution, limit of detection is lowered 500 times (0.22 µg/mL) and the sensitivity increased 20 times (0.04192 (µg/mL)-1). Results: Binding was very specific. Signal amplification strategy is practical. Further applied to planar electrode for optimizing sensing, response time in less than 1 minute. Conclusions: This is the first report of T detection using electrochemical method based on non-Faradaic impedance. h antigen density and interactions of antigens will help physicians to determine the clinical efficacy and resistance mechanisms to targeted antibodies like T and ado-Trastuzumab.For the first time, we have established a low cost, highly sensitive, fast, synthetic, QCM assay which could be used as a basis for developing a new generation of affinity-based Immunosensor assays. This real time capability and its simplicity of operation are highly suitable for multipurpose studies on living cells including cell immobilization, cytotoxicity of drugs, and the cell action mechanisms
Efficacy and safety of the combination of pertuzumab (P) plus trastuzumab (T) plus docetaxel (D) for HER-2 positive metastatic breast cancer (MBC) in pretreated patients (pts) with trastuzumab in the neo/adjuvant setting: A real-life study.
Authors: Ricciardi Giuseppina , Ficorella Corrado , Iezzi Laura , Marchetti Paolo , Pizzuti Laura , Prestifilippo Angela , Schifano Silvia , Maimone Sergio , Adamo Vincenzo 
Published: September 2018

e12516 Background: The discovery of new anti-HER2 targeted therapies has significantly improved the outcomes in the metastatic setting. However, the population enrolled in clinical trials is not always representative of the clinical practice. Moreover, only 7% of breast cancers (BCs) present as metastatic disease at the first clinical observation. In most cases, metastatic disease is diagnosed in pts with a history of BC already treated in the neo/adjuvant setting. This latter subgroup is largely under-represented in clinical trials. The aim of this study was to assess in real-life the efficacy and safety of dual HER2 blockade as 1st line in Trastuzumab-pretreated pts in the neo/adjuvant setting. Methods: This is a multicenter, observational, retrospective study conducted in 6 Oncology Italian Centers. Primary end-points: progression free survival (PFS) and overall survival (OS). Secondary end-points: response rate and cardiac safety. PFS and OS curves were estimated using the Kaplan-Meier method. Tumor response was assessed according to RECIST 1.1 and safety with CTCAE v4.0. Results: We evaluated 35 HER2-positive MBC from November 2013 to December 2016, 60% with tumors Luminal B, 40% HER2-enriched. The most common metastatic sites were: lung (20%), lymph nodes (14.3%) and liver (11.4%). Median (m) age: 50 (range 20-71), mECOG PS 0 (range 0-1). At a m follow-up of 55.6 months (mos) (range 6-170), all pts were evaluable for efficacy and safety. The m number of cycles administrated was 6 (range 2-10). The mPFS was 12 mos (95% CI 2-38). The mOS was 15.2 mos (95% CI 2-36). 14.3% of pts had a complete response, 60% a partial response and 25.7% a stable disease. m baseline LVEF was 65%, final LVEF 61%. Conclusions: Our preliminary data confirmed the efficacy and no increase in cardiac toxicity of the combination Pertuzumab, Trastuzumab and Docetaxel in Trastuzumab-pretreated pts, mirroring the PFS data but not the OS reported in the Cleopatra study. A longer follow-up for OS is needed for a comprehensive evaluation of the antitumor activity of dual-HER2 blockade in Trastuzumab-pretreated pts.
Methylation signatures of circulating tumor DNA for hormone therapy response in ER+ breast cancer patients (pts).
Authors: Liu Xiao-ran , Liang Xu , Tie Jian , Shao Bin , Zhang Jia-yang , Chen Lingbo , Li Hui-ping , Che Jianwei , Gong Hao , Fu Yuan 
Published: September 2018

e12542 Background: ER+/PR+ breast cancer patients receiving hormone therapy have shown vary prognosis. To predict the effectiveness of hormone therapy in these patients, genome and transcriptome markers were attempted with very limited success. It has been shown that alterations of methylome are common and dynamic in breast cancer tissues. For instance, therapeutic intervention and disease status can modify of methylation profile of the certain genomic regions. Therefore, it offers an alternative method to identify relevant biomarkers and study the mechanism of different drug response. Methods: In this study, we utilize whole genome methylation sequencing (WGMS) method to profile the circulating tumor DNA (ctDNA) of ER+ breast cancer patients. Compared with traditional tissue samples, ctDNA offers unique advantages for convenient sample collection and more importantly monitoring the changes in near real time. Total 6 consecutive pts receive exemestane treatment from 2013 to 2016 were recruited at Peking University Cancer Hospital. ctDNA samples from these 6 pts were collected at baseline and time of progression during the course of exemestane treatment. Results: 2 out of 6 pts showed initial resistance to exemestane and the rest were responding, and one pts eventually developed resistance after 18 months. Through WGMS, we identified differentially methylated regions (DMRs) by dividing the samples into sub groups based on the disease progression (67.1Mb of DMRs) and drug response (24.8Mb of DMRs). ER+/PR+ breast cancer related genes were found in the DMRs, such as human estrogen receptor alpha gene (ESR1), which showed significantly correlation with drug response. Pts resistant to exemestane were found to have high methylation level of the ESR1. In addition, genes such as TGFBR2, CDH1, GSTP1, and MLH1 were also found differentially methylated. Conclusions: In summary, our data shows that the methylation status of some gene regions is varied among pts according to exemestane response. These DMRs may contribute to exemestane sensitivity, which are being further explored in subsequent studies with expanded number of patients.