bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiofrequency ablation for early-stage breast cancer: results from 5 years of follow-up in a prospective multicenter study.
Authors: Kinoshita Takayuki , Yamamoto Naohito , Fujisawa Tomomi , Takahashi Masato , Aogi Kenjiro , Hojo Takashi , Tsuda Hitoshi , Yoshida Masayuki 
Published: September 2018

e12098 Background: Given the increasing number of early-stage breast cancers detected by screening mammography, we aim to establish RFA as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase 1 study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Building on these results, we designed a Phase 2 clinical trial to investigate the efficacy of a non-surgical RFA procedure. Methods: From Nov. 2009 to Nov. 2012, 58 patients with early-stage breast cancer received non-surgical RFA therapy. Patients had localized solitary N0 tumors with a maximum diameter of 1 cm. They underwent RFA and sentinel lymph node biopsy under general anesthesia and adjuvant therapy and breast irradiation. Follow-up evaluation for residual tumor at 3, 6, and 12 months after RFA included clinical breast examination, diagnostic imagings (ultrasound, magnetic resonance, and mammography), and vacuum-assisted biopsy. Surgical resection was recommended for patients with suspected residual disease or incomplete ablation. The primary endpoint was the frequency of adverse events. Secondary endpoints included the complete ablation rate and ipsilateral breast relapse-free rate. The diagnostic performance of the follow-up examinations and cosmetic outcomes were evaluated for exploratory purposes. Results: The follow-up period ranged from 450 to 2552 days (median, 1832 days). The 57 patients completed the non-surgical RFA procedure and underwent diagnostic imaging and needle biopsy after 3 months. Seven patients with suspected incomplete ablation underwent surgical resection; incomplete ablation was confirmed in 5 (8.6%, 2 with invasive and 3 with non-invasive ductal carcinoma). During subsequent follow-up, 1 patient each was diagnosed with contralateral breast cancer and brain tumor. No ipsilateral breast tumor relapse or distant recurrence was documented. Cosmetic results were excellent in 94% of patients. Conclusions: RFA is a promising alternative to surgery for treating localized, early-stage breast cancers. Clinical trial information: UMIN000008675.
Features of p53 expression in residual tumors in Russian women after neoadjuvant chemotherapy of breast cancer stage T1-3N0-1.
Authors: Kolyadina Irina Vladimirovna , Poddubnaya Irina , Pavlikova Olga , Komov Dmitrii , Andreeva Yulia , Frank Georgii , Vishnevskaya Yana V 
Published: September 2018

e12121 Background: Residual tumor is an important prognostic factor after neoadjuvant therapy, however, p53 expression in the residual breast tumors poorly understood. Methods: In our study included 164 Russian women (24-76, median age - 47) with breast cancer stage T1-3N0-1 treated in RCRC from 2004 to 2016. Biological subtype of primary tumor was luminal A (8,1%), luminal B HER2-negative (43,6%), luminal HER2+ (15,4%), triple negative (22,8%) and non-luminal HER2+ (10,1%). After neoadjuvant chemotherapy by anthracycline ± taxanes (in HER2+ cancer ± trastuzumab) patients had radical surgery. We analyzed pathological response after neoadjuvant therapy and features of p53 expression in residual tumors. Results: The rate of pCR was 23% for all women, and was a very various for biological type (luminal A – 0%, HER2- luminal B - 11%, HER2+ luminal - 38%, triple negative – 35% and HER2+ non-luminal - 50%), p=0,003. In 15% cases pathological response was a very similar to pCR, in 62% - was low. In analyze of 38 residual tumors we found p53 low expression (<10% stained cells) in 66% cases and high (>10% stained cells) - in 34%. We did not find any correlation between p53 rate in residual tumors and stage, Ki67 and PR-status (p>0,05). But p53 expression strongly correlated with age, tumor grade and biological type (p<0,05). So, high rate of p53 was found more often in women <45 years (50%) vs women 45-59 years (15,4%) and patients 60 years older (20%), p=0,04. All G1-tumors was p53-negative, p53 high expression was seen in 29% of G2 tumors and 80% - G3, p=0,04. The high rate of p53 residual tumor was seen in luminal A subtype in 0%, HER2- luminal B – 30%, HER2+ luminal – 75%, triple negative -50%, HER2+ non-luminal - 100%, p=0,01. Conclusions: High expression of p53 in the residual tumors after neoadjuvant chemotherapy is associated with younger age and unfavorable biological characteristics that may be a very important for the further prognosis in breast cancer.
Neutropenic complications with neo/adjuvant adriamycin and cyclophosphamide in early stage breast cancer patients: A prospective study at the McGill University health center.
Authors: Saleh Ramy , Elkrief Arielle , Afshar Elmira , Azoulay Laurent , Meterissian Sarkis H. , Bouganim Nathaniel 
Published: September 2018

e12127 Background: We prospectively investigated the incidence of neutropenic complications (NC) with neo/adjuvant AC (doxorubicin and cyclophosphamide) chemotherapy (CTX) among early-stage breast cancer (ESBC) patients. NC was defined as febrile neutropenia (FN), dose delay/reduction or need of granulocyte colony-stimulating factors (G-CSF) to proceed with CTX. Methods: This was a single-center, observational, prospective cohort study conducted at the McGill University Health Center. All ESBC patients who received AC regimen as neo/adjuvant CTX between February 2016 and February 2017 were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of predictors of NC were estimated using Cox-proportional hazards models. Results: A total of 118 patients, corresponding to 409 cycles of AC were analyzed. Most patients underwent Q3week cycles (83.1%). Median age was 52 years old (IQR 43-61). Prophylactic G-CSF was given to 20 dose-dense patients and 10 Q3weeks patients. In patients not receiving prophylactic G-CSF, 57 (65.5%) manifested at least one episode of NC (corresponding to an incidence rate of 26.4%/cycle of CTX [95% CI: 20.0%-34.2%]), of which 9 developed FN requiring hospital admission. In the final prediction model, body mass index < 25 kg/m2(HR: 2.36, 95% CI: 1.16-4.78) and increasing glucose levels (HR: 1.56, 95% CI: 1.14-2.14) were significantly associated with NC. Baseline absolute neutrophil count (ANC) was protective. Conclusions: The incidence of NC in our prospective study is significantly higher than previously reported in retrospective studies (26.4% vs. 12%). Normal BMI and high glucose were associated with the highest risk of NC. More importantly, 65% of ESBC on AC will require G-CSF during their treatment due to a NC episode. [Table: see text]
Duration of neoadjuvant endocrine therapy and breast cancer outcomes.
Authors: Mougalian Sarah Schellhorn , Soulos Pamela R. , Lannin Donald R. , Pusztai Lajos , Gross Cary Philip , Killelea Brigid K. 
Published: September 2018

e12129 Background: Interest in the use of neoadjuvant endocrine therapy (NET) has increased over the past decade, and recent studies have demonstrated similar response rates compared to neoadjuvant chemotherapy. We examined the associations between duration of NET and type of surgery and change from clinical stage to pathologic stage. Methods: We used the National Cancer Data Base to identify women diagnosed with stage II-III, ER and/or PR positive breast cancer who received endocrine therapy from 2004-2014 and underwent surgery. We classified patients according to timing and duration of NET. We performed logistic regression to examine the impact of NET duration on likelihood of 1) receiving breast conserving surgery (BCS) versus mastectomy and 2) being downstaged. Downstaging was defined as pathologic stage lower than clinical stage and upstaging as pathologic stage higher than clinical stage. Results: In our sample of 159,676 patients, 6584 received NET (4.1%). NET was more frequently used in older women with multiple comorbid conditions, larger tumors, and higher nodal stage. The highest rates of NET were in academic/research or integrated network cancer programs. Of patients who underwent NET, 26.5% received it for ≤3 months, 41.0% for 3-6 months, 27.7% for 6-12 months, and 4.9% for 12-24 months. Patients who received NET for 3-6, 6-12, and 12-24 months were all significantly more likely to receive BCS versus mastectomy than patients who did not receive NET (Table). Patients who underwent NET compared to adjuvant endocrine therapy were more likely to be downstaged (Table). Conclusions: The most common duration of NET was 3-6 months, but >26% of patients received NET for less than 3 months. Longer durations of NET were strongly associated with BCS and downstaging. Further research is needed to determine the population of patients mostly likely to benefit from NET and the optimal length of treatment. [Table: see text]
Discrepancy of pathologic complete response and outcome between breast tumor and axillary node in HER2 positive breast cancer after neoadjuvant chemotherapy.
Authors: Chen Shin-Cheh , Chang Hsien-Kun , Lin Yung-Chang , Shen Shih Che , Kuo Wen-Lin , Yu Chi-Chang , Chou Hsu-Huan , Huang Yi-Ting , Ueng Shir-Hwa 
Published: September 2018

e12503 Background: The pathologic complete response (pCR) rate in primary tumor and axillary node after different chemotherapy regimens of neoadjuvant chemotherapy (NAC) in HER2 positive breast cancer (BC) is unknown, the impact of pCR on disease free survival (DFS) and overall survival (OS) is still controversial. Methods: A cohort of 350 HER2 positive BC (296 cytologically proved axillary node metastasis) received NAC with different regimens, antracyclin with taxotere (AT), docetaxel with transtuzumab (DT) and docetaxel with transtuzumab and pertuzumab( DTP) between 2005 and 2016 in a large medical center were analyzed retrospectively. The impact of pCR rates of breast and axillary node on DFS and OS were analyzed. Results: Of 350 women with HER2 positive BC received NAC, median age was 50 years(18~93), median tumor size was 4.3 cm, the pCR rates of breast and axillary node were 16.2% and 28.7% ( P= 0.018) in patients received AT( n= 130) , 47.6% and 66.9% ( P= 0.00028 ) in patients received DT( n= 191) ,65.5% and 77.8% ( P= 0.372 ) in patients received DTP( n= 29), respectively. The 5-year DFS were 79.3% and 66.0% ( p= 0.0023), 5-year OS were 89.5% and 76.6% ( P= 0.0201) in patients with breast pCR and non-pCR, respectively. The 5-year DFS were 75.7% and 58.4% ( P= 0.00037), 5-year OS were 85.7% and 72.6% ( P= 0.0024) in axillary pCR and non-pCR patients, respectively. The 5-year DFS were 79.3% and 75.7% ( P= 0.430), and 5-year OS were 89.5% and 85.7% ( P= 0.695) in breast and axillary pCR, respectively . The 5-year DFS in breast pCR whom received targeted therapy (DT and DTP groups) was significantly better than whom not received targeted therapy (AT groups), 85.3% and 65.0% ( P= 0.039), respectively Conclusions: Higher pCR rate in axillary node than breast was found in this cohort. Either pCR in axillary node or breast was associated with improved DFS and OS, but no difference of DFS and OS between breast and axillary pCR . The 5-year DFS in breast pCR received targeted therapy were significantly better than breast pCR patients received chemotherapy alone.
Effects of erybuline/capecitabine (EC) treatment in very elderly women (VEW) with MBC.
Authors: Russo Antonio , Bazan Viviana , Carreca Ignazio Ugo , Cicero Giuseppe , Carreca Anna Paola 
Published: September 2018

e12508 Background: Eribuline mesylate, is widely prescribed for MBC pts alone or in combination with Capecitabine in patients pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&T). Elderly Patients (EP) develop rapid and sometimes fatal toxicity during treatments due to pharmacokinetic features of these drugs.A combination schedule (E+C) to evaluate its suitability for VEW with MBC patients ,was used in this study. Methods: Treatment plan: E 0.96 mg/sqm IV on d1 every 21d - C 900 mg/sqm bid d1-14 every 28d (Dose-adjustement if necessary was according to Kintzel-Dorr’s formula for elderly), schedule administration continued until progression or intolerable toxicity . Eligibility criteria: histologically confirmed diagnosis of BC, 1 or more measurable lesion,(bone or visceral ) not brain mts, age > 75 years, failure of previous treatment with A or T , Comprehensive Geriatric Assessment evaluation (CGA) permissive for chemotherapy, adequate renal (CCl evaluation), bone marrow and liver function. Charlson's Score Comorbidity Scale was also considered. Evaluations tools: Clinical Benefit (CB) as Stable Disease + Objective Response Rates according to ESMO CB scale v.2a, Toxicity Profile using CTCAE v3.0 Criteria and Quality of Life (QoL) score through EORTC QLQ-C30 questionnaires V.3. Results: From 2014 jan to 2016 dec ,39 metastatic VEW, mean age 83.5 were treated and 37 are still under maintenance therapy (2 pts discontinued treatment for personal reasons). A total of 659 cycles were delivered to the 37 pts without any G4 toxicity. No delay in therapy delivery was needed. QoL score shows no worsening with improvement in about 79% after treatment in comparison with baseline. Clinical Benefit was evaluated about 80%. Conclusions: A further period of monitoring allowed to confirm our previous report in this setting with this combination schedule. It appears more fit with comorbidity or frailty than other chemotherapy regimens for MBC. The analysis of preliminary data shows a non-inferiority vs other usual treatments ,more suitability for very elderly women. An enlarged polycentric study is ongoing in order to confirm these outcomes.
Cerebellar metastases as the only brain metastatic site and correlation with molecular characteristics of primary breast cancer.
Authors: Tomasevic Zorica , Tomasevic Zoran , Grujicic Danica , Kovac Zeljko , Milovanovic Zorka , Minic Ivana , Kolarevic Daniela 
Published: September 2018

e12509 Background: Contrary to well recognized higher incidence of brain metastases (BM) in HER2 3+ and triple negative (TN) BC, correlation with BC molecular subtypes and cerebellar metastases is not well explored. Methods: From January 2007 to Jun 2016, 269 patients with BCBM have been prospectively registered at the Institute for Oncology and Radiology of Serbia. We analyzed metastases localization within brain, and identified 28 patients with cerebellar metastases. Correlation with molecular subtype of primary BC, median time to cerebellar metastases development, treatment and survival were also analyzed Results: 28 patients (10.4%) of median 47 years (29-63) had cerebellar metastases as the only brain metastatic site confirmed by CT/MRI. Median time to cerebellar BM was 21 months (range 0-141). Cerebellum was the first distant metastatic site in 20/28 patients (71.4%), and 8 (28. 5%) patients had inoperable BC and/or distant metastases before cerebellar metastases development. Molecular subtype of primary BC was known for 27/28 pts (96.4%): 21 pts (77.7%) had HER2 3+BC; 14 (52%) had ER/PR negative BC and there were no TNBC. Fifteen patients (53.5%) were treated with brain surgery + postoperative WBRT, 4 (14%) with gamma knife, while remaining 9 pts (32%) underwent WBRT only. Patients with good performance (PS 0-2) also received various systemic treatments +/- trastuzumab/ lapatinib. Mean survival upon cerebellar metastases was 19.2 months (median 9, range 2-123+ months); 39% patients were alive after 12 months; 21% after 24 months; 14% after 36 months. One patient (3.6%) is alive without relapse/progression 123 months+ after cerebellar metastases extirpation; trastuzumab is ongoing through all that period. Conclusions: Majority of analyzed patients with cerebellar metastases had HER2 3+ BC (77.7%). It is also interesting that none of patients within this group had TNBC Therefore, it seems reasonable to speculate that some still unrecognized BC and/or cerebellar soil characteristic, contribute to HER2 3+ BC predilection to cerebellum in this rare patient subgroup.
Development of a breast and lung cancer research panel to target therapeutically relevant copy number and gene fusion variants from blood.
Authors: Bagai Varun , Schageman Jeoffrey , Brinza Dumitru , Li Yanchun , Gu Jian , Bramlett Kelli 
Published: September 2018

e12518 Background: With recent advances in next-generation sequencing (NGS) technologies, it is now possible to detect somatic mutations with allele frequencies in blood samples as low as 0.1% from circulating tumor DNA. A natural extension to this achievement is adding the ability to simultaneously detect copy number variants and gene fusions. A panel such as this addresses a full repertoire of variant classes found to be linked with certain tumors and would enable researchers additional tools to profile cancer samples more dynamically thus enriching current diagnostic tool sets. Here, we present progress on such an approach and apply current NGS technology to achieve our goals. Methods: Samples were sequecned using the Ion S5™ system. Results: Using control samples, we can reproducibly demonstrate detection of ERBB2 (HER2/neu) gene amplifications with high statistical significance and as low as a 2 fold difference versus non-amplified loci in titration experiments. In addition, this ERBB2 gene amplification was detected in the context of a validated breast cancer somatic mutation panel in which no negative impact was exhibited and mutation detection specificity and sensitivity were both greater than 90%. Lastly, we developed an additional panel to detect gene fusions relevant to lung cancer. Using the titration approach above, the EML4-ALK fusion variant was shown to have a limit of detection near 1% with no negative impact on detection sensitivity and specificity when combined with the validated lung cfDNA somatic mutation panel. Conclusions: From the outcomes of these experiments, we have shown the ability to reproducibly and simultaneously detect copy number and gene fusion variants as well as somatic mutations at very low limits of detection in a cell free DNA background derived from blood samples.
Pre-clinical analysis of the CDK4/6 inhibitor palbociclib in HER2-positive breast cancer.
Authors: ElChaarani Bilal , Stires Hillary , Pohlmann Paula Raffin , Riggins Rebecca 
Published: September 2018

e12520 Background: There has been substantial progress in treatment of metastatic HER2+ breast cancer, unfortunately, treatment progression of the disease is universal. Palbociclib is an oral cyclin-dependent kinase (CDK) 4/6 inhibitor that is FDA approved in combination with endocrine therapy for treatment of patients with ER+ metastatic breast cancer. Here we present pre-clinical studies in HER2+ breast cancer cell lines investigating whether addition of palbociclib to the combination of trastuzumab and pertuzumab (TP) is an effective therapy, and whether we could identify predictive biomarkers for palbociclib in this setting. Methods: Crystal violet assays to measure growth of BT-474 (HER2+, ER+), SKBr3 (HER2+, ER-) and MDA-MB-361 (HER2+, ER+ but resistant to TP) were performed in the presence and absence of TP (5 µg/ml each) with increasing concentrations of palbociclib (25-500 µg/ml). Western blots were performed in the presence and absence of TP with and without palbociclib to demonstrate efficacy of TP (blocking phosphorylation of HER2), palbociclib (blocking phosphorylation of Rb), and expression of NIMA-related kinase 2 (NEK2), an established downstream target of CDK4 in HER2+ breast cancer cells. Results: We found growth inhibition in response to palbociclib as single agent in a dose-dependent manner in BT-474, SKBr3, and MDA-MB-361 cells (P < 0.05). Treatment with TP prevented growth in BT-474 and SKBr3 cells to such a great extent that an additive effect between TP and palbociclib was not detectable. However, treatment with palbociclib maintained a dose-dependent decrease in growth in the presence of TP in MDA-MB-361 cells (P < 0.05). Western blots showed decreased expression of pHER2 in response to TP in BT-474 and SKBr3, but not in MDA-MB-361. Treatment with palbociclib decreased pRB in BT474, SKBr3, and MDA-MB-361 with or without TP. NEK2 expression, however, was not affected in any of these cell lines. Conclusions: Palbociclib has an inhibitory effect in resistant and non-resistant HER2-positive cell lines suggesting palbociclib represents an alternate targeting pathway for growth inhibition. Our initial work did not show reliable biomarkers to predict palbociclib effects.
Safety of trastuzumab in women with HER2+ breast cancer.
Authors: Nowsheen Somaira , Aziz Khaled , Park Jae Yoon , Villarraga Hector R. , Herrmann Joerg , Ruddy Kathryn Jean 
Published: September 2018

e12522 Background: Trastuzumab is widely used in management of HER2+ breast cancer patients. A known adverse effect of trastuzumab use is cardiac dysfunction, which can often be reversed with cessation of therapy. Our objectives were to 1) assess if trastuzumab can be safely administered to breast cancer patients with reduced cardiac function and 2) identify patient characteristics that predict susceptibility to trastuzumab-induced cardiac dysfunction. Methods: A retrospective analysis was performed on female patients seen at Mayo Clinic for HER2+ breast cancer and treated with trastuzumab for localized or metastatic disease between January 1, 2000 and August 31, 2015. Eligibility criteria included documentation of and results from at least one echocardiogram prior to and at least one after trastuzumab initiation. Left ventricular (LV) ejection fraction (EF) of 53% or more was considered normal. Any LVEF reduction of 10% or more was considered significant. Among patients with normal EF, age strata of < 45, 45-60, and > 60 at time of trastuzumab initiation were used to assess risk factors for clinically diagnosed cardiac dysfunction (defined as EF < 53 or abnormal strain and physical symptoms of heart failure (HF)). Results: We identified 335 women (mean age 53.3, with 25.3% age < 45, 44.5% age 45-60, and 30.1% age > 60) who had normal LVEF (median EF 64, range: 53-75) and 23 women (mean age 53.4, with 30.4% age < 45, 43.5% age 45-60, and 26.1% age > 60) who had low LVEF at baseline (median EF 52, range: 25-52). Approximately a third (34.3%) of women with normal LVEF prior to initiation of therapy had at least one subsequent echocardiogram showing a drop of 10% or a low LVEF ( < 53). Approximately a quarter (26%) of women with low LVEF at baseline had a 10% drop in LVEF. HF incidence increased with age. Predictive factors for trastuzumab-induced cardiac dysfunction were obesity and history of coronary artery disease (CAD) across all age strata, and chest irradiation (IR) for those aged 45-60 only. Conclusions: Our results suggest that trastuzumab can be administered in women with reduced cardiac function at no greater risk than in those with preserved cardiac function. Some women with no obesity, history of CAD, or history of chest IR may not need echocardiograms during trastuzumab therapy.