bluuebunny/crossref_metadata_2025 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.
Safety and antitumor activity of weekly carboplatin plus paclitaxel in metastatic breast cancer: A ten years, single-institution, retrospective analysis.
Authors: Vernieri Claudio , Milano Monica , Mennitto Alessia , Maggi Claudia , Ferrari Benvenuto , Rinaldi Lucia , Mennitto Roberta , Stefanetti Claudia , Re Barbara , Mariani Gabriella , Capri Giuseppe , Bianchi Giulia Valeria , De Braud Filippo G.
Published: September 2018

e12556

Background: Safety and activity of weekly carboplatin plus paclitaxel in patients (pts) with metastatic breast cancer (mBC) are poorly known. Nevertheless, taxane-based chemotherapy (ChT) is the milestone in mBC treatment. In this retrospective analysis, we report the safety and clinical activity of this combination in a consecutive series of pts treated at IRCCS Fondazione Istituto Nazionale dei Tumori in Milan in the last decade. Methods: We collecteddata on mBC patients treated between January 2007 and December 2016 with carboplatin AUC 2 plus paclitaxel 80 mg/m2on days 1 and 8, every three weeks. Selection criteria were: ECOG 0-1; evaluable and/or measurable mBC; known estrogen and progesterone receptors (ER/PgR) status and HER2 expression levels. 274 pts fulfilled the selection criteria, and 265 pts were evaluable for response and survival. Response was assessed according to RECIST criteria. Results: The median number of administered cycles was 6 (range 1-17). 66.4% and 88.3% of pts had received taxanes or antracyclines, respectively, as an adjuvant treatment or in the metastatic setting. 97% of HER2+ pts received trastuzumab concomitant with ChT. Among patients with ER/PgR-positive tumors, 42.8% received different endocrine treatments as maintenance therapy after achieving the best response with ChT or due inacceptable toxicity. Hematological and gastrointestinal toxicities were the most frequent adverse events (AEs), and were severe in 19% and 1.2% of pts, respectively. In particular, G3-G4 neutropenia and febrile neutropenia occurred in 16.8 % and 1.9 % of pts, respectively. 10.2% of pts discontinued the treatment because of toxicity. The objective response rate was 44.8% in the overall population, with median progression free survival (mPFS) of 8.6 months and median overall survival (mOS) of 23.7 months. Conclusions: Weekly carboplatin plus paclitaxel is a well-tolerated and active regimen across all different molecular subgroups of mBC. [Table: see text]
Feasibility and preliminary results of A Lifestyle Intervention via Email (ALIVE) in minority breast cancer survivors.
Authors: Paxton Raheem , Hajek Richard , Newcomb Patricia , Taylor Wendell , Chang Shine , Courneya Kerry S. , Parra-Medina Deborah , Jones Lovell
Published: September 2018

e12573

Background: Prior data have indicated that minority breast cancer survivors are receptive to participating in lifestyle interventions delivered via email or the Web. In this study, we examined the feasibility and preliminary results of A Lifestyle Intervention via Email (ALIVE) in a sample of racial and ethnic minority cancer survivors. Methods: Survivors (Mean age = 52, 83% African American) were recruited and randomized to either a 3-month physical activity or a dietary condition. Descriptive statistics and mixed-effects models were computed to examine the behavioral and evaluation outcomes. Results: Forty-four of 71 survivors who participated in the baseline assessment completed the study. Survivors in the physical activity condition compared to the diet condition made greater improvements in leisure time physical activity (+272 vs. +120 Metabolic equivalent minutes per week; P < 0.01) and greater reductions in sedentary time (-304 vs. -59 minutes/week; P < 0.01). No significant time-by-group interactions were observed for our diet variables; however, positive trends among survivors in fruit and vegetables (+0.7 cup servings/day, P < 0.01) were observed in the dietary condition. Feasibility data from survivors indicated that most survivors would recommend ALIVE to other cancer survivors (97%), were satisfied with ALIVE (82%), and felt that ALIVE was effective (73%). Survivors expressed concerns about the automated calls and functionality of the ALIVE e-mails. Conclusions: ALIVE appears to be feasible for racial and ethnic minority cancer survivors and shows promising results for implementation in larger and ethnically diverse cohorts. Functionality changes are warranted to boost adherence rates. Clinical trial information: NCT02722850.
Efficacy and safety of eribulin in patients with metastatic breast cancer at early and late application: Real-life experience.
Authors: Manzyuk Valentina , Gorbunova Vera , Kovalenko Elena , Bolotina Larisa V , Semiglazova Tatiana , Ponomarenko Dmitry , Zhilyaeva Larisa , Mukhametshina Venera , Karabina Elena
Published: September 2018

e12579

Background: We sought to describe treatment patterns of eribulin and clinical outcomes associated with early and late use among anthracycline and taxane-pretreated patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between Jan1, 2014 and Jan 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 113 MBC patients were considered by 16 providers. A median age was 53 (44-58) yrs and ECOG status 0-1 were assessed. 57 (50,5%) pts were ER/PR-positive, 37 (32,7%) – triple-negative, 19 (16,8%) – HER2-positive (in combination with trastuzumab). Most of the pts (96,5%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of MBC treatment to 36 (32%) pts (early application), the 3rd and later lines (late application) – to 77 (68%) pts. Clinical response rate (ORR and SD ≥ 6 months) was 44% among early line treated patients (first and second-line combined) and 38% among late line eribulin treated patients. Median PFS was 4,89 months (95% CI 2,84-8,00) among early users and 3,96 months (95% CI 2,04-7,99) among later users. The effectiveness in early eribulin application group was higher, but difference was not statistically significant. Tolerability of the drug was good: withdrawn due to toxicity had 3,5%, dose reduction – 13, 3% of pts. The most common type of toxicity was hematological with neutropenia Gr II in 12 (10,6%) of pts and Gr III – in 8 (7,1%) of pts and 2 pts had febrile neutropenia. 6 (5,3%) pts experienced fatigue Gr II. Peripheral neuropathy Gr II was observed in 8 (7,1%) of pts. Conclusions: This is the first real-life description of clinical outcomes, for patients initiating eribulin therapy for MBC throughout the Russian Federation. Our experience with Eribulin in MBC patients confirms it efficacy and safety in early lines of treatment and intensively pretreated patients.
RNA-Seq to reveal mitochondrial gene fusions in breast cancer.
Authors: Agrawal Vartika , Cheung Yee Him , Keswarpu Payal , Somlo George , Abu-Khalaf Maysa , Sikov William M. , Varadan Vinay , Harris Lyndsay , Dimitrova Nevenka
Published: September 2018

e13019

Background: Several mitochondrial DNA (mtDNA) mutations have been identified in various types of human cancer. While gene fusions encoded by the nuclear genome have an important role in tumorigenesis, the contribution of the mitochondrial genome to this process is unclear. mtDNA has limited protective mechanisms compared to that for nuclear DNA (nDNA), and hence more susceptible to genomic aberrations. Methods: We sequenced RNA from pre and post treatment breast cancer samples obtained from neoadjuvant clinical trials BrUOG 211A/211B. Seventy-three of these samples were considered baseline and 61 were from post-treatment samples, 54 samples at both time points. Patients were given a run-in dose of bevacizumab (B), nab- paclitaxel (N) or trastuzumab (T), followed by combination biologic/chemotherapy (HER2- with B/carboplatin/N; HER2+ with T/carboplatin/N). RNA was derived from biopsy pairs obtained pre/post 10-day exposure to run-in monotherapy. We used TopHat-Fusion and deFuse for fusion detection. Results: On average, in each patient 4.6 mtDNA gene fusions were detected at the baseline and 4 in the post treatment samples. In this cohort we detected in total 385 mtDNA fusions across the baseline and 344 across the post-treatment samples. A number of fusions had recurrently shown drastic increase from baseline to post-treatment, such as MT-ATP6:MT-ND2 ( N = 9), MT-ND6:MT-CO2 ( N = 6), MT-ND6:MT-CO1 ( N = 10), and MT-ND4:MT-ATP6 ( N = 9). We observe that some mitochondrial genes such as MT-ND6 have as many as 7 gene partners. MT-ND6 appeared in fusions that were most abundant among both baseline and post-treatment samples with MT:ND4 ( N = 39), MT:ND2 ( N = 37) and MD:ATP6 ( N = 36). Interestingly, gene fusions MT-ND6:J01415.25, MT-CYB:MT-ND2 and MT-ND6:MT-ND1 were observed respectively in 9, 5 and 4 baseline samples but not in their post treatment equivalent. Conclusions: While several studies have examined the presence of mtDNA mutations in breast cancer, the role of mitochondrial gene fusions is unknown in cancer. In our breast cancer cohort we observed quite a high number of mitochondrial fusions, and some of them seem to be recurrent in multiple samples. This could potentially have clinical implications as knowledge of fusions in solid tumours gains.
Germline cancer susceptibility mutations in older women with breast cancer (BC).
Authors: Chavarri Guerra Yanin , Sand Sharon , Brown Sandra , Hendricks Carolyn B. , Hander Mary , Weeman Kisa , Nadesan Suhasini , Segota Zdenka E , Cheng Howard Ho Wing , Hurria Arti , Soto Perez De Celis Enrique , Nehoray Bita , Kuzmich Lily , Solomon Ilana , Rybak Christina , Blazer Kathleen Reilly , Van Tongeren Lily Ravel , Blankstein Kenneth Bruce , Weitzel Jeffrey N.
Published: September 2018

e13030

Background: Older women with BC are less likely to undergo genetic cancer risk assessment since a hallmark of hereditary BC is younger age at onset. Hence there are limited data regarding genetic risk assessment findings in older women with BC. We analyzed the clinical characteristics and germline variant profiles of women with history of BC referred for genetic counseling at age ≥ 65 years, enrolled in the Clinical Cancer Genomics Community Research Network registry. Methods: Women age ≥ 65 with a history of BC (invasive or ductal carcinoma in situ) who underwent genetic testing from 1997 to 2016 were included. The profile of those found to have BC-related pathogenic variants was analyzed. Demographic and clinical characteristics for those with and without germline variants were compared using Fisher’s test and x2statistics. Results: 1372 women age ≥ 65 with BC were identified. Genetic testing was performed in 75% (n = 1035), among whom 10.4% (n = 108) had a germline variant in a BC-associated gene. High risk gene variants accounted for 85.1% (n = 92): BRCA2 (41.6%, n = 45), BRCA1 (37%, n = 40), PALB2 (5.5%, n = 6) and TP53 ( < 1%, n = 1). Moderate risk gene variants were identified in 16.6% (n = 18): CHEK2 (13.8%, n = 15), ATM (1.8%, n = 2) and NF1 ( < 1%, n = 1). Mean age at BC diagnosis was 56.4 (range 29 - 84) for women with variants and 60.9 (range 20 - 90) for those without (p < .001). 25.9% of women with variants (n = 28) had their first BC diagnosed ≥ age 65, of which 60.7% (n = 17) were BRCA2 and 21.4% (n = 6) were BRCA1 mutations ( BRCA2 was significantly higher in women diagnosed with BC age ≥ 65 [p < .001]). There was no difference in the mean number of 1st, 2nd and 3rd degree relatives with BC (2.4 [range 0-10] vs 2.2 [range 0-15]) for women with and without variants, respectively, and no difference in stage at diagnosis (Stage I-II in 95% vs 89.5%, p = .4). Women with variants were less likely to have ER/PR positive tumors than those without (66% vs 81.6%, p = .01). Conclusions: BC related susceptibility variants, particularly in BRCA2, are found in a significant number of older women undergoing genetic testing for a first diagnosis of BC ≥ 65. Older women with a clinical suspicion of hereditary BC should not be excluded from genetic testing and counseling based on chronological age alone.
Association of atypia in ductal lavage and breast cancer risk.
Authors: De Censi Andrea , Cazzaniga Massimiliano , Casadio Chiara , Chiapparini Laura , Gandini Sara , Guerrieri-Gonzaga Aliana , Macis Debora , Veronesi Paolo , Bonanni Bernardo
Published: September 2018

e13040

Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment will greatly benefit from sampling cellular material from the target tissue. Ductal lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from and BC risk are lacking .We studied the prevalence of atypia in DL and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model > 1.66% or > 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimens and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 vs 11 in women with or without atypia (21% vs 10%; log-rank p = 0.05, Cox model adjusted for age p = 0.02). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL may predict the onset of BC in high-risk women. The reversal of atypia in DL as a surrogate biomarker of BC risk reduction warrants investigation.
Breast tumor location in BRCA mutation carriers and implications for prevention.
Authors: Hosseini Ava , Esserman Laura , Wallace Anne M. , Khoury Amal , Au Alfred , Mukhtar Rita ,   ASCO
Published: September 2018

e13048

Background: Although pathogenic mutations in the BRCA gene are known to confer a high risk of breast cancer, close to 65% of mutation carriers do not opt for prophylactic mastectomy. These women are managed with intense screening, which does not aid in prevention. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk (0.39-0.61 relative risk reduction), and can be modified to target specific areas of the breast. Given that most sporadic breast cancers involve the upper outer quadrant, we wondered if a majority of tumors in BRCA mutation carriers would also be confined to one quadrant, or if they would be equally distributed throughout the breast given the high baseline risk present. Identifying a particularly high risk area of the breast could potentially allow for the use of targeted cosmetic mammoplasty as a novel method of risk reduction. Methods: We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning > 1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squared test. Results: Mean age at breast cancer diagnosis was 44 years. Mean tumor size was 2.2 cm (0.1-7cm) with mean distance from the nipple of 4.8 cm (1-12 cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant (54%, with the other quadrants having 11-17% of tumors respectively) whether or not multicentric tumors were included in the analysis (p < 0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p = 0.021). Conclusions: More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that breast reduction mammoplasty targeting removal of the upper outer quadrant could significantly reduce breast cancer risk. For those women who choose not to have prophylactic mastectomies or are not yet ready, these data support an intermediate step to help decrease breast cancer risk, which warrants further study.
Short breast MRI screening trial in women at high-risk for breast cancer.
Authors: Scoggins Marion , Dogan Basak , Ma Jingfei , Wei Wei , Song Jong Bum , Candelaria Rosalind P , Litton Jennifer Keating , Arun Banu
Published: September 2018

e13049

Background: The American Cancer Society (ACS) recommends yearly breast MRI (BMRI) in addition to mammography for women with high breast cancer risk. However, standard BMRI protocols have a long acquisition time and consequently long interpretation time, which can reduce patient compliance and drive MRI cost. Therefore, we aimed to evaluate an American College of Radiology (ACR)-compliant short BMRI (SBMRI) protocol vis-à-vis compared with standard of care BMRI (SOC-BMRI) obtained in the same high-risk patient. To the best of our knowledge, a prospective study comparing both techniques does not exist. Our primary endpoint is to compare positive predictive value and cancer detection rate. Secondary endpoint is measuring and comparing patient experience between two techniques. As the study and accrual is ongoing and primary endpoint will be evaluated at the completion of accrual in a blinded fashion, here we report characteristics of patients who participated so far. Methods: This is a prospective HIPAA compliant and IRB approved trial. High risk women undergoing SOC-BMRI based on ACS screening guidelines signed an informed consent form to undergo an additional SBMRI within 7 days of the SOC-BMRI. Accrual target goal is 200 patients to give statistical power to estimate sensitivity and 95% confidence interval, with 10% or less expected to have breast cancer. Results: A total of 59 women were enrolled so far. Median age is 53 (range 26-72). Nine (15.3%) had BRCA1 or BRCA2 pathogenic mutations; 6 (10.2%) variant of uncertain significance (VUS). One (1.7%) had CDH1 pathogenic mutation, one (1.7%) had VUS in PALB2. Personal history of breast cancer was present in 2 (3.4%), atypical hyperplasia in 9 (15.3%), LCIS in 3 (5.1%), family history (FH) of breast cancer in 55 (93.2%). Hormone replacement therapy use was current in 2 (3.4%), past in 10 (16.9%). Use of raloxifene, tamoxifen, or aromatase inhibitors was current in 8 (13.6%), past in 5 (8.5%). Conclusions: In this BMRI study comparing SOC-BMRI versus SBMRI, the distribution of breast cancer risk factors reflects our routine cohort, with most patients screened based on FH of breast cancer. Clinical trial information: Primary ID 2015-0243 Secondary IDs NCI-2015-02031 Clinicaltrials.gov ID NCT02590458.
Body mass index, hyperglycemia, and stage of presentation at time of cancer diagnosis in Hispanic women.
Authors: Gonzalez Pagan Omayra J. , Rodriguez Joe J , Orengo Juan C , Di Marco Anna Maria
Published: September 2018

e13052

Background: Obesity prevalence among Hispanic communities is alarmingly high. The correlation between obesity and elevated blood glucose levels with increased cancer risk has remained controversial for several years. Thus, the main objectives of this study are: 1) to estimate the prevalence of obesity and overweight in a women cancer population; 2) to compare our findings with the general population; 3) to assess the stage at time of diagnosis by cancer site. Methods: An exploratory, cross-sectional study was conducted at one oncology women clinic located in Ponce, Puerto Rico. The medial records were selected by a Simple Random Sampling, all adult women with any type of cancer were included. Descriptive statistics were used to summarize patient demographics, morbidity, and clinical characteristics. Results: 216 medical records were reviewed. The distribution by age group was: 21-30 (n = 3 (1.4%); 31-35 (n = 35 (16.2%); 46-64 (n = 96(44.4%); ≥65 (n = 82(38%). The 50.5% (109) of the patients presented breast cancer, 24 (11.2%) uterine cancer and 17 (7.9%) colon cancer. FBS ≥ 126 was presented by 38 participants (19.6%). A BMI ≥ 30 was presented by 121 (56%) of the patients and 54 (25%) were overweight (81% of obesity and overweight). Obesity and overweight in women from Puerto Rico Behavioral Risk Surveillance System (PRBRFSS, 2014) presents a prevalence of 64% and Loren et al (2014) found a prevalence of 65.1% in women without cancer, comparing with our finding (81%) this difference is statistically significant (p < 0.05). A 26.9% (n = 58) of Hispanic women in our study presented diabetes vs 17.2% in the Hispanic women population (PRBRFSS, 2015) this difference is statistically significant (p < 0.05), controlling by cancer diagnosis. Analyzing stage (from I to IV) by breast cancer or not, we found a significant statistically difference (p < 0.001), 83.9% of breast cancer are stage I and II vs. 45.3% of no breast cancer. Conclusions: Our results suggest that a BMI ≥ 25 kg/m2 and diabetes are part of the profile of the Hispanic women with a diagnosis of a malignancy. Breast cancer is diagnosed at an earlier stage than any other malignancy, which could be explained by the amount of information available for breast cancer screening.
A single-center study of cancer and chemotherapy-induced kidney disease.
Authors: Mirza Abu-Sayeef , Mushtaq Sarah , Reddy Revati , Mousa Mina , Bohra Chandrashekar , Kongpakpaisarn Kullatham , Verma Sean , Mhaskar Rahul Suresh , Jaglal Michael Vishal , Bassil Claude
Published: September 2018

e13062

Background: It is clinically understood that chronic kidney disease (CKD) and cancer are interrelated. Yet, few studies measure how renal outcomes vary according to common malignancies and common therapeutic agents. We report the incidence and the nature of CKD among cancer patients from a single institution. Methods: A retrospective chart review of cancer patients managed in the onconephrology clinic at the Moffitt Cancer Center from 05/01/2015 to 07/31/2016 was conducted. Patients with acute or chronic kidney disease secondary to a malignancy or side effect of chemotherapy were included in this study. Renal function outcomes were recorded at three-month follow-up intervals from the 15-month duration. Results: Out of the total 88 patients with median age of 68 years, 63 patients were diagnosed with chronic kidney disease, whereas the remaining had acute kidney injury. Kidney cancer and multiple myeloma represented the largest proportion with 12 patients each. Patients with kidney cancer had a mean creatinine of (2.35, 1.74) mg/dl compared to patients without kidney cancer with creatinine (1.97, 1.07) mg/dl. Abdominal cancers had the highest proportion of chronic kidney disease (84.21%) whereas 81.48% of patients with genitourinary cancers had chronic kidney disease. Patients prescribed tyrosine kinase inhibitors had a lower average estimated glomerular filtration rate (28.37, 9.86) mL/min/1.73 m2 compared to other chemotherapeutic agents, though this was a weakly significant relationship (p-value = 0.07). Similar renal outcomes according to malignancy and chemotherapy are reported. Conclusions: This group of patients demonstrated the frequency of chronic kidney disease differs depending on the type of malignancy or chemotherapy. A multidisciplinary approach involving oncologists and nephrologists should be adopted to prevent further renal damage from cancer and its therapies.
Striking age differences of multiple myeloma (MM) diagnosis in patients of Indian and Pakistani descent in the United States compared to native countries.
Authors: Unnikrishnan Athira , Khan Abdullah Mohammad , Narayan Preeti , Norkin Maxim
Published: September 2018

e13070

Background: Several studies from India and Pakistan have reported a median younger age of MM diagnosis as compared that of western population. The exact reason for the younger age of myeloma diagnosis in this population is not well understood. Methods: We used the SEER database to analyze age of MM diagnosis in subjects of Indian and Pakistani descent in the United States and compared it to the published data of MM diagnosis in India and Pakistan. Patients with ICD—O-3 morphologic codes (9732/3) and race code 15/16/17 identifying Asian Indians and Pakistanis were identified in the SEER registry data (1973-2013). Data on year of diagnosis, race, sex and age were collected. Four published retrospective studies involving local Indians or Pakistanis patients identified using PUBMED. Average Median age and male to female ratio (M: F) was calculated in both groups and compared for any difference Results: 146 myeloma patients of either Indian or Pakistani descent were identified from the SEER registry. The median age of diagnosis was 67 years with a mean age of 66.1 years. The male to female ratio was 1.41. The retrospective studies analyzed had a total of 495 myeloma patients with median age at diagnosis of 56 years and male to female ratio of 2.01, suggesting that multiple myeloma presented almost a decade earlier in native Indian and Pakistani patients compared to their US counter parts. Conclusions: Subjects in India and Pakistan were significantly younger at the time of MM diagnosis as compared to subjects of Indian and Pakistani descent diagnosed with MM in the US suggesting an environmental factor involved with myeloma genesis in subjects living in India and Pakistan. [Table: see text]