bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relapse-free survial and target identification to enhance response with neoadjuvant and adjuvant dabrafenib + trametinib (D+T) treatment compared to standard-of-care (SOC) surgery in patients (pts) with high-risk resectable BRAF-mutant metastatic melanoma.
Authors: Wargo Jennifer Ann , Amaria Rodabe Navroze , Prieto Peter A. , Andrews Miles Cameron , Tetzlaff Michael T. , Futreal Phillip Andrew , Hwu Patrick , Hwu Wen-Jen , Glitza Isabella Claudia , Tawbi Hussein Abdul-Hassan , Cormier Janice N. , Lee Jeffrey Edwin , Patel Sapna Pradyuman , Simpson Lauren , Burton Elizabeth M. , Bassett Roland L. , Ross Merrick I. , Gershenwald Jeffrey E. , Davies Michael A. , Woodman Scott Eric 
Published: September 2018

9587 Background: Targeted and immune therapies have dramatically improved outcomes in stage IV metastatic melanoma pts. These agents are now being tested in earlier-stage disease. SOC surgery for high-risk resectable melanoma (AJCC stage IIIB/IIIC), with or without adjuvant therapy, is associated with a high risk of relapse (~70%). We hypothesized that neoadjuvant (neo) + adjuvant treatment with D+T improves RFS in these pts. Longitudinally collected biospecimens from pts receiving this treatment were analyzed to identify candidate strategies to further improve outcomes. Methods: A prospective single-institution randomized clinical trial (NCT02231775) was conducted in BRAF-mutant pts with resectable Stage IIIB/C or oligometastatic stage IV melanoma. Pts were randomized 1:2 to SOC (Arm A) versus neo + adjuvant D+T (Arm B; 8 wks neo + 44 wks adjuvant). The primary endpoint was RFS. Tumor biopsies were collected at baseline, week 3, and at surgery for molecular and immune profiling (whole exome sequencing, gene expression profiling, IHC, flow cytometry). Results: 21 of a planned 84 patients were enrolled (Arm A = 7, Arm B = 14). Arms were well balanced for standard prognostic factors, and toxicity was manageable. RECIST response rate with neo D+T was 77%, and the pathologic complete response rate (pCR) was 58%. First interim analysis revealed significantly improved RFS in the D+T arm over SOC (HR 62.5, p < 0.0001), leading to early closure to enrollment. Pts with a pCR at surgery had significantly improved RFS versus pts without pCR (p = 0.04) on neo D+T. Tumor profiling revealed incomplete MAPK pathway blockade and higher levels of CD8+ T cells expressing immunomodulators Tim-3 and Lag-3 in pts who did not achieve a pCR. Conclusions: Neo + adjuvant D+T is associated with a high pCR rate and markedly improved RFS over SOC in pts with high-risk resectable BRAF-mutant metastatic melanoma. pCR at surgery is associated with improved RFS. Tumor analyses reveal candidate targets for testing in future trials to enhance responses to neo D+T. Clinical trial information: NCT02231775.
Financial toxicity and cancer-related distress among melanoma survivors.
Authors: Buzaglo Joanne S , Miller Melissa F , Zaleta Alexandra K , Johnson Jamese , Gupta Niraj K. 
Published: September 2018

9588 Background: Melanoma survivors are at risk for significant financial burden due to cancer care and out of pocket costs. We explored 1) the financial impact of melanoma and its relationship to cancer-related distress, and 2) survivors’ experiences discussing financial burden with their health care team. Methods: Of 110 melanoma survivors enrolled in the Cancer Support Community’s online Cancer Experience Registry, 56 completed questions about financial impact of cancer and cost of care communication. Participants rated concern (0 = not at all; 4 = very seriously) about 27 items encompassing psychological, emotional, physical and practical concerns; items were summed into a total distress score (mean = 33, SD = 21, range 0-88). Financial impact and overall distress were examined via regression analysis. Results: Participants were 71% female, 89% Caucasian, median age 54, and median time since diagnosis 2.5 years. Total annual income: 34% < $60K; 46% $60K+; 20% not reported. 24% spent $101-250/month on melanoma out of pocket costs; 20% spent $251-500; and 24% spent ≥$500. The top concern was health insurance/money worries (69% moderately to very seriously concerned). Due to medical costs, 57% depleted their savings, 20% borrowed against or used retirement money, 20% used pharmaceutical assistance programs, 13% skipped medicine dosages at least sometimes, and 17% postponed filling prescriptions. Only 28% reported that their health care team spoke to them about cost of care, and 28% were asked about financial distress; 42% desired financial assistance. Financial impact was associated with an increase in overall distress for those with income < $60K (p < .05; interaction p < 0.05). Conclusions: Substantial proportions of melanoma survivors experience financial burden that can impact quality of life, particularly lower income individuals. Although oncologists are encouraged to discuss treatment costs, most patients report they have not had these discussions with providers. These results support the development/evaluation of interventions to enhance doctor-patient communication, and financial counseling to minimize financial burden of melanoma and the risks it can confer for quality of life, course of cancer care, and health outcomes.
Whole genome and RNA sequencing reveal the distinct genomic landscape of acral melanoma.
Authors: Kong Yan , Chi Zhihong , Si Lu , Sheng Xinan , Cui Chuanliang , Dai Jie , Ma Meng , Wu Xiaowen , Tang Huan , Yu Jiayi , Yan Junya , Yu Huan , Xu Tianxiao , Guo Jun 
Published: September 2018

9589 Background: Acral melanoma is a common subtype of melanoma in Asians with extremely poor prognosis, and therapy strategy has not been clearly established for acral melanoma. The aim of this study is to perform genomic and RNA profiling of acral melanoma to obtain the comprehensive genomic view of this subtype of melanoma. Methods: Genomic DNA was extracted with Qiagen DNeasy Blood or Tissue Kit . DNA libraries were prepared using a CancerPROTM-P88 BOX library Prep kit and sequencing was performed using the Illumina HiSeq X10. RNA was isolated with Qiagen RNeasy mini-spin column. cDNA was synthesized from total RNA using the SuperScript III first-strand synthesis system . RNA libraries were prepared using the NEBNext Ultra II Directional RNA Library Prep Kit and sequencing was performed using the Illumina HiSeq X10. Results: To obtain a comprehensive genomic and functional genomic view of acral melanoma, we sequenced the genomes of 14 acral melanoma and transcriptomes of 11 of these melanoma samples. We found a new mutation in the V28 codon of BRAF in three patients. Furthermore, we identified recurrent non-synonymous single nucleotide variants in previously described oncogene NRAS, as well as in genes encoding keratin associated proteins (KRTAP4-7, KRTAP4-5) and mucin (MUC2, MUC21). Notably, a recurrent noncoding hotspot mutation was discovered in 4 of 11 cases. By analyzing the RNA sequencing data, we found significant divergence on transcriptome between patients with or without ulcer. In total, we identified 201 genes were significantly up-regulated and 386 genes significantly down-regulated in acral melanoma patients with ulcer. Differentially expressed genes were enriched in pathways associated with cancers, melanogenesis, cell death signaling, skin diseases, etc. Conclusions: Our study reveals potentially different driver mutations and distinct transcriptome in acral melanoma patients compared with cutaneous melanoma patients and sheds lights to the further personalized medicine for acral melanoma patients.
Adherence to tamoxifen in Mexican young women with breast cancer.
Authors: Villarreal-Garza Cynthia Mayte , Martinez-Cannon Bertha Alejandra , Castro-Sanchez Andrea , Platas Alejandra , Fonseca Alan , Vega Yoatzin , Barragan-Carrillo Regina , Mohar Alejandro , Bargallo-Rocha Enrique , Bojoquez-Velazquez Karen 
Published: September 2018

e12003 Background: Young age has been associated with significantly increased risk of breast cancer (BC) death among women with luminal BC. One contributing factor might be the low rate of tamoxifen (TMX) adherence previously reported in this young group. Given that in Mexico a disproportionate rate of BC is diagnosed among YW, information regarding TMX adherence is particularly relevant. Our study's aim was to report TMX adherence in Mexican YW and its associated determinants. Methods: Consecutive patients ≤40y at diagnosis at the National Cancer Institute in Mexico City, under TMX treatment, completed a multiple-choice survey regarding the use and attitudes about hormonal therapy and adherence. Data of TMX disposal was collected from the pharmacy’s records, and the medication possession ratio (MPR) was calculated; an MPR ≥80% was considered adherent. Results: 135 YW with a median age at diagnosis of 35.7y (24-40) were included. 77% were undergraduate, 28% unpaired and 33% childless. Median follow-up was 26 months. 95% of patients reported a regular TMX intake: 70% did not miss any doses, while 25% missed 1-6 doses a month. Only 45% considered that the information received regarding TMX therapy was sufficient and for 37% was incomprehensive. 43% thought TMX significantly reduced their recurrence-risk and 60% strongly believed that they needed to be on TMX treatment. 73% of women reported adverse effects, being menopausal symptoms the most frequent, but only 27% were worried about the treatment long-term effects. From the 99 patients with a pharmacy record, 73% had an MPR > 80%. No significant factor was statistically associated with TMX adherence. Conclusions: Although Mexican YW and pharmacy data surprisingly sustained higher rates of TMX adherence compared to previous data, still a significant proportion of patients were non-adherent. Two-thirds of our patients reported having adverse effects, which might contribute to late TMX discontinuation. Since the newer recommendations of double hormonal blockade could lead to higher withdrawal rates of endocrine therapy in YW, adherence should be emphasized and closely monitored. Accordingly, hormonal treatment adherence should be a key component in the medical assessment of young luminal BC patients.
Ki 67 analysis and prognostic factors in women with luminal breast cancer.
Authors: Vissotto Eduardo De Figueiredo , da Costa Alexandre Andre Balieiro Anastácio , Boente Leonardo de Azevedo , Ricardo Eliza Dalsasso , Costa Felipe D'Almeida 
Published: September 2018

e12024 Background: After screening became available for most women, breast cancer is diagnosed mainly in early stage. The decision to offer adjuvant chemotherapy to patients with luminal breast cancer is not easy and the knowledge of prognostic factors is mandatory. Ki 67 plays an important role in this context, especially in patients who do not have access to genetic signatures. Nevertheless, data available about the optimal cutoff of Ki 67 to predict luminal B subtype is still controversial. Methods: We evaluated Ki 67 and other clinical-pathological factors of women with non-metastatic hormone-positive breast cancer in a major oncologic hospital. The objective was to determine the impact of Ki 67 on the disease free survival (DFS) and the optimal cutoff. This is a retrospective cohort of patients of the AC Camargo Cancer Center between January 2007 and January 2009 selected by a random sample of convenience. Ki 67 analysis was performed through tissue-microarray (TMA). Log rank test and Cox regression were used to test the prognostic value of each variable for DFS. The optimal Ki 67 cutoff was defined plotting a curve for the hazard ratios for each Ki67 cutoff point tested and their 95% confidence intervals. Results: We evaluated 195 patients with a median follow up of 58 months. The optimal cutoff of Ki 67 was 23% for DFS (HR 3,78; CI 95% 1,3 – 10,76; p 0,012). The cutoffs of 20%, 30%, 40% and 50% were also statistically significant. The kappa concordance index between TMA and whole tissue sections was 0,567 (CI 95% 0,268-0,866; p = 0,003). Other poor prognosis factors on the surgical samples were higher histologic grade, presence of vascular-lymphatic invasion and mythotic index superior to 10 mytoses per high powerfield. On the biopsy samples, inflammatory infiltrate absent or low was found to be a poor prognostic factor Conclusions: Analysis of Ki 67 in women with non-metastatic hormone-positive breast cancer is a prognostic factor for DFS, with different cutoffs. This may suggest that Ki 67 should be considered as a continuous variable rather than a dichotomized value. Analysis of others clinical-pathological factors are still important for therapeutical decision.
A comparison of genomic assays in determining risk of late recurrence and benefit of extended endocrine therapy (EET).
Authors: Raque Kathleen , Rico Lina Marie , Yu Eddy , Carter W. Bradford , Frazier Thomas G. 
Published: September 2018

e12045 Background: Breast cancer patients who are ER positive, lymph node negative have the best overall prognosis. However 50% of recurrences occur after 5 years. The Breast Cancer Index (BCI) is a gene expression-based biomarker that provides an individual risk of distant recurrence and benefit of EET based on a continuous risk model. (1) The BCI may help with clinical decisions regarding EET since prolonged therapy may have an increase in side effects including uterine cancer, DVT, myalgias and bone loss. The OncotypeDX is a 21 gene assay that predicts recurrence with a recurrence score. A recent study by Wolmark et al. evaluated the use of quantitative Estrogen Receptor Index (ESRI) combined with RS and found that RS was prognostic in patients with higher quantitative ESRI, suggesting EET be used for patients with intermediate and high RS with ESR1 expression > 9.1. (2) Methods: 20 patients, ER positive, node negative who had the BCI and ONC-DX performed were evaluated in this retrospective IRB approved review. Results: Using ESRI alone 85% of patients would be recommended to continue an additional 5 years of EET. Using BCI this number was reduced to 35%. Conclusions: Comparing both the risk of recurrence and benefit of ETT, ESRI and BCI were concordant only 37.5% of the time. The cost of extended adjuvant therapy with Anastrazole ($190/mos x 60 mos = $11,400) or Tamoxifen ($50/mos x 60 mos = $ 3,000) would have resulted in a cost savings of $79,800 (Anastrazole) or $21,000 (Tamoxifen) for this small group of patients. Utilization of the BCI (cost $ 3416.00) may be a cost effective and accurate genomic approach in determining the use of EET and avoiding concomitant side effects.
Early breast cancer in elderly patients: Characteristics, therapy, and long-term outcome.
Authors: Gal Omer , Ishai Yael , Hendler Daniel , Neiman Victoria , Zoref Dalia , Brenner Baruch , Yerushalmi Rinat 
Published: September 2018

e12046 Background: The number of older adults diagnosed with breast cancer and the number of breast cancer survivors is on the rise. The majority of women with breast cancer are diagnosed with an early stage (non-metastatic) potentially curable disease. However, data regarding breast cancer characteristics, treatment, and survival for elderly women are sparse. Methods: We retrospectively reviewed all women with invasive, non-metastatic breast cancer treated in our tertiary medical cancer center from January 2004 to December 2007. Patients were divided into 2 groups: those aged 65-75 years and those aged >75 years. Data on tumor characteristics, treatment modalities, and outcome were retrieved from the patient computerized medical files and compared between the groups. Results: The study group comprised 390 patients. Of them, 252 were aged 65-75 years, and 138 were aged >75 years. Patients were followed for a median of 10.6 years.Tumor characteristics were similar in both groups, although older patients had larger tumors at diagnosis. Patients aged >75 years underwent more mastectomies, but were less likely to receive axillary surgery or adjuvant systemic therapy. When grouped according to subtype (luminal, Her-2+, triple-negative), an independent effect on recurrence rate and overall survival (OS) for both age and subtype was observed with the worst outcome in the women with triple-negative disease aged >75 years, and best outcome in the women with Her-2 positive aged 65-75 years (p=0.16 for recurrence, p <0.001 for OS). The median OS for the follow-up period was 10.3 years for women aged 65-75 years and 8.0 years for women aged >75 years. The disease-free survival rate after 8 years of follow-up was 88% for the younger women and 85% for those aged >75 years (p=0.27). Conclusions: The current study reveals the physicians' approach in treating breast cancer in the elderly age groups. It demonstrates the impact of both age and tumor subtype on recurrence rates and OS. Triple-negative disease had the worst outcome in both age groups. Physicians should be aware of the impact of the different breast subtypes on outcome in the older patients subgroup and consider treatment based on the individual patient comorbidities and life expectancy.
Incidence of esophageal and head and neck cancers among breast cancer survivors in the United States.
Authors: Dollar Krista , Tyker Albina , Simpson Matthew , Adjei Boakye Eric , Dombrowski John J. , Varvares Mark A , Osazuwa-Peters Nosayaba 
Published: September 2018

e12054 Background: Late sequelae of breast cancer therapies potentially impact morbidity and mortality with increasing numbers of survivors. Radiation exposure has been linked to increased incidence of second primary cancers (SPC). However, to date, there is limited literature describing incidence of head and neck (HN) and esophageal cancers in patients with an index breast cancer (BC). This study aimed to describe the incidence of esophageal and HN cancers following breast cancer diagnosis. Methods: Standardized incidence ratios (SIRs) were calculated using the Surveillance, Epidemiology, and End Results (SEER) 9 database for BC patients diagnosed from 1973-2013. SIRs compared incidence of HN and esophageal cancer after an initial BC diagnosis to the general population. HN included oral cavity, pharynx, and larynx. BC patients were grouped into those who received radiotherapy for their breast cancer (n = 216,045) and those who did not (n = 289,596). SIRs were calculated in 5-year intervals. SEER does not contain information on chemotherapy. Results: Less than 1% of BC patients developed HN (0.3%) or esophageal cancers (0.1%), irrespective of radiation treatment. However, among patients with an index BC who received radiation therapy, there was significant but small increased incidence of HN and esophageal cancers five to nine years following treatment (HN SIR: 1.22; 95% CI, 1.04-1.43 and esophagus SIR: 1.44; 95% CI, 1.09-1.87). Esophageal cancer incidence continued to increase through 15 years of follow-up, however incidence of HN was not significant beyond ten years after the index BC diagnosis and radiation treatment. Conclusions: Compared to the general population, breast cancer patients have elevated incidence of HN and esophageal cancers detected five to nine years after receiving radiation treatment, but only the incidence of second primary esophageal cancer remains elevated at 15 years. These findings warrant further investigations of breast cancer radiation and future malignancies.
Bone health management in early breast cancer patients: An Italian osteoncology center experience.
Authors: Recine Federica , Bongiovanni Alberto , Fausti Valentina , Mercatali Laura , Riva Nada , Calpona Sebastiano , Faedi Marina , De Vita Alessandro , Liverani Chiara , Spadazzi Chiara , Miserocchi Giacomo , Foca Flavia , Vespignani Roberto , Rocca Andrea , Amadori Dino , Ibrahim Toni 
Published: September 2018

e12055 Background: Bone health evaluation is important for the optimal management of early stage breast cancer (BC) both in post and pre-menopausal setting. Adjuvant endocrine therapy (ET), including luteinizing hormone-releasing hormone (LHRH) analogues with tamoxifen (TAM) and aromatase inhibitors (AI), may affect bone health resulting in a reduction of the bone mineral density (BMD), leading to an increased risk of bone fractures. The objective of this observational study performed at an Italian Osteoncology Center was to evaluate the prevalence of vertebral fractures in pre and post women with BC treated with adjuvant ET. Methods: Data on patients (pts) with early BC were collected from 2011 to 2016 in a single Institution. We investigated the prevalence of vertebral fractures in pre and post pts treated with ET and other potential independent risk factors associated to bone fractures. To evaluate association with bone fractures and clinical factors, univariate logistic models were carried out. P-value of less than 0.05 was considered significant. Results: A total of 1,165 women with early pre and post-menopausal BC were evaluated; for 702 (60.2%) pts treated with ET was available a X-Ray of the spine and they were included in the analysis. The median age was 61 year-old (31-86 y). A total of 124 were pre-menopausal and 578 were post-menopausal pts. Frequency of bone fractures was 17.6% in post-menopausal and, among them, the major risk of bone fractures was associated with AI treatment (OR:4.37, p:0.005); in pre-menopausal pts bone fractures incidence was 6.4% and the major risk was associated to LHRH+AI treatment (OR:2.18, p:0.307). Higher risk of bone fractures was associated with presence of back-pain (OR:1.81, p:0.006), a lower BMD (OR:2.91, p: < 0.001 for pts with BMD≤2.5) and lower level of Vitamin D (OR:2.06, p:0.030 for pts with ≤10) in univariate analysis. Further analysis are ongoing. Conclusions: This Italian experience confirms the importance of bone health evaluation in order to prevent bone fractures in the management of pre and post-menopausal early BC treated with ET.