bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.