bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family history of breast cancer in non-BRCA male breast cancer: A case-control study.
Authors: Calip Gregory Sampang , Exten Katherine Rebecca , Rauscher Garth H , Brown Krystal , Bernhisel Ryan , Kidd John , Saam Jennifer , Lancaster Johnathan , Hoskins Kent 
Published: September 2018

e13032 Background: Approximately 85% of male breast cancer (MBC) patients test negative for a BRCA mutation, and the role of genetic predisposition is unclear. Cancer risk counseling for unaffected relatives of BRCA-negative MBC patients relies on accurate cancer risk estimates, but there is limited data on the risk of breast cancer (BC) for relatives of these men. We characterized the association between MBC and family history of BC in patients who test negative for BRCA mutations in order to facilitate cancer risk counseling and to explore the possibility of unidentified MBC susceptibility alleles. Methods: We performed a case-control study of patients who had full length sequencing and large-rearrangement analysis for germline mutations in BRCA1/2 or the mismatch repair (MMR) genes at a commercial laboratory from 2006-2012. Cases were MBC patients who tested negative for a BRCA1/2 mutation (n = 3,647); controls were male colon cancer patients who tested negative for mutations in MMR genes (n = 4,269). Information on family history of BC was ascertained from test request forms completed by the ordering healthcare provider at the time of testing. Unconditional multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between family history of BC in first- (FDR) and second-degree relatives (SDR) and MBC with adjustment for potential confounders (age, ethnicity, year of testing). Results: Compared to controls, MBC cases had higher odds of BC in a FDR or SDR (OR = 4.7; 95% CI 4.1, 5.3). Associations were strongest for family history of BC in 1 female FDR (OR = 3.9; 95% CI: 3.3, 4.6), ≥2 female FDR (OR = 7.5; 95% CI 5.0, 11.4), BC in a FDR < 45 years old (for cases diagnosed < 45, OR = 6.9; 95% CI 3.9, 12.4), a male FDR or SDR with BC (OR = 17.9; 95% CI 7.6, 42.1), and both a male and female FDR or SDR with BC (OR = 15.7; 95%CI 4.4, 55.3). Conclusions: MBC patients who test negative for a BRCA mutation have significantly higher odds of reporting family members affected by breast cancer, particularly with affected FDR < 45 years old, multiple affected relatives, and male relatives with BC. This data can guide risk counseling in MBC families, and suggests the existence of unidentified MBC susceptibility alleles.
Ultrasound-guided mammotome for diagnosis and minimally invasive excision of mammary clustered calcifications.
Authors: Hu Wei 
Published: September 2018

e13034 Background: To validate the ultrasound-guided vacuum-assisted breast biopsy system (Mammotome) for diagnosis and minimally invasive excision of calcification in breast. Methods: In 20 patients, breast calcification lesions diagnosed by mammography were excised by ultrasound-guided Mammotome system with 8-gauge probe. The samples were taken mammography and followed by pathological examination. Results: All lesions were removed accurately and thoroughly with satisfactory cosmetic outcomes. No clinically significant hematoma developed. Each mass was resected through 9.15±2.70 cores on average over a mean of 11.65±3.88 minutes. Two cases of them were histologically diagnosed as ductal carcinoma in situ and 8 cases were fibroadenoma and 10 cases were adenosis. Conclusions: Ultrasound-guided Mammotome system can profit to diagnose and treat breast calcification lesions which is ultrasound positive. Ultrasound detection rate of microcalcifications is up to the instrument resolution and the operator's experience and patience.
Influence of insulin therapy for type 2 diabetes mellitus on cancer incidence.
Authors: Cho Oyeon , Oh Young-Taek , Chun Mison , Noh O Kyu , Heo Jaesung 
Published: September 2018

e13036 Background: This study aimed to investigate the influence of insulin therapy for type 2 diabetes mellitus (T2D) on cancer development. Methods: We evaluated 4780 patients with T2D, treated at our institution, from 1994-2006, after excluding patients with 1) preexisting cancer or cancer within 1 year after T2D registration, 2) renal transplantation, and 3) follow-up period of < 5 years. The following information was collected from the patients’ electronic medical records: age; sex; registered date of T2D and cancer; last visit; use of metformin, insulin, and medications for microvascular complications; and start date of using insulin in the first year after cohort entrance. Insulin users were stratified according to insulin start date and complication as follows: < 3 months with (462 patients) or without complications (526 patients), ≥3 months with complications (852 patients) or without complications (1249 patients). The standardized incidence ratio (SIR) was calculated using the expected age-standardized incidence rate in Korea. The adjusted hazard ratio (AHR) of insulin was estimated for evaluation of all-year cancer risk and time interval of 3 years from cohort entrance. Results: SIR was > 1 in all cancer types except laryngeal and esophageal cancers. The median follow-up was 12 years (interquartile range: 9–15 years), and 679 events occurred. Insulin users had a significantly higher risk of all-time cancer. The patients with insulin use for ≥3 months without complications had a continuously increasing cancer risk 2–3, 4–6, 7–9, 10–12, and 13–15 years from cohort start (AHR [95% confidence interval {CI}]: 2.2 [0.91–5.3], P= 0.081; 2.39 [1.07–5.32], P= 0.0335; 1.98 [1.35–2.9], P= 0.0005; 2.41 [1.52–3.81], P= 0.0002; and 1.6 [0.6–2.83], P= 0.1077, respectively), while the rest did not. This was significantly associated with stomach, colorectal, lung, liver, pancreatic, and bladder cancers (AHR [95% CI]: 6.09 [2.58–14.4], P= 00001; 2.49 [1.22–5.07], P= 01188; 3.36 [1.18–9.51], P= 0.02265; 14.8 [1.97–110], P= 0.0088; 14.6 [1.88–113], P= 0.0103; and 10.4 [2.38–45.6], P= 0.00186, respectively). Conclusions: Incidences of gastrointestinal, lung, and bladder cancers could be increased in new insulin users without complications.
Risk factors associated with mortality among women with breast cancer in Haiti.
Authors: Bernard Joseph , Pascal Garvey Rama , Raymond Sarah Cassandra , DeGennaro Vincent 
Published: September 2018

e13069 Background: According to recent estimations of GLOBOCAN 2012, breast cancer is the 2ndmost common cancer among Haitian women. This study aims to describe the epidemiology of breast cancer at a Haitian hospital and to determine the factors associated with mortality. Methods: A retrospective chart review was conducted on women treated for breast cancer at the Innovating Health International Cancer Center, in Port-au-Prince, Haiti. All charts with complete information from 2014 and 2015 were included. Charts were reviewed to collect key variables related to breast cancer. Odds ratios were calculated and Mantel-Haenszel Chi-square test was used to identify the factors associated with mortality. Results: Among the 289 charts reviewed, 275 were selected for this study. The mean age is 51.82 years-old [20 - 100]. 81.1% of the patients had stage III or IV breast cancer at their first consultation. 92% of the women were diagnosed with invasive ductal carcinoma. Of the 165 cases tested for hormone receptor status, 54.5% were ER-positive, 31.5% were triple negative and 12.1% were HER2-enriched. The mortality rate is 24.4%. The odds of dying from breast cancer was significantly higher among women who had their menarche before 15 years old [Odds Ratio (OR) = 4.2; P = 0.02], stage III or IV breast cancer (OR = 3.7; P = 0.01), triple-negative or HER2-positive breast cancer (OR = 2.5; P = 0.01). Mortality was significantly lower among women who benefited from hormone therapy (OR = 0.22; P < 0.01). Conclusions: Breast cancer is often diagnosed at late stages in Haiti, which increases mortality. Women with ER-positive breast cancer survive significantly more than those with HER2-positive or triple-negative breast cancer, mainly due to the availability of hormone therapy and the absence of trastuzumab. A national awareness and screening program has to be implemented to educate Haitian women on breast cancer and increase early diagnosis. As an essential medicine in oncology according to the World Health Organization (WHO), biosimilar trastuzumab needs to be available to increase the survival of patients with HER2-positive breast cancer.
Association of body mass index (BMI) and stage in patients with non-small cell lung cancer harboring KRAS mutations.
Authors: Bhatt Ananta , Mueller Catherine , Gui Jiang , Dragnev Konstantin H. , Tafe Laura J. 
Published: September 2018

e13071 Background: Body mass index (BMI) is inversely associated with lung cancer risk, particularly in former or current smokers. KRAS mutant non-small cell lung cancer (NSCLC) has been shown to be highly associated with smoking status. Therefore, we sought to investigate the association of BMI and stage in a cohort of patients with KRAS mutant NSCLC. Methods: Patients with KRAS mutant lung cancer who underwent tumor genotyping using next generation sequencing testing were identified. BMI( kg/m2 ) was categorized as: Underweight ( < 18.5), normal weight (18.5 – 24.9), overweight (25-29.9) and obese (≥30). Chi-square and t-tests were performed to test association between stage (I vs. II+) and BMI (4 categories), and stage and BMI as a continuous variable, respectively. Results: From 5/2013 to 9/2016, 201 patients with KRAS mutant NSLC were identified. Of these, 178 (88.6%) were current or former/ever smokers (SM) and 23 (11.4%) were never smokers (NS). In the SM group, 114 were female and 64 male with a median age at diagnosis of 66.5 years (range 45-93). In the NS group, 15 were female and 8 male with a median age at diagnosis of 71.5 years (range 51-92) (age for NS vs. SM p = 0.0439). Fifty-two (25.9%) patients presented with stage I disease, 149 (74.1%) presented with advanced (stage II-IV) disease. There was no significance in the BMI at diagnosis of SM vs. NS or by sex. There was a difference (p = 0.0430) in the BMI between patients with stage I disease (mean 28.6) and patients with stage II or greater disease (mean 26.6). This was also seen in SM with stage I vs. II+ disease (p = 0.0417); however, this was no longer significant in SM when broken out by sex or in NS alone. Conclusions: We identified a significant difference in BMI in patients with KRAS mutant NSCLC with stage I vs. advance stage disease, with a higher BMI associated with early stage disease at diagnosis. The lower BMI in patients with more advanced stage may be a confounding variable explained by comorbidities, and the lung cancer itself. It is unlikely that treatment effects were a factor as the KRAS testing was done prior to initiating therapy. Further studies looking at BMI and survival analysis in patients with mutant KRAS NSCLC are warranted.
Complementary and alternative medicine use and hormonal therapy initiation in women with hormone receptor-positive breast cancer: The BQUAL study.
Authors: Greenlee Heather , Neugut Alfred I. , Shi Zaixing , Hillyer Grace , Buono Donna , Mandelblatt Jeanne S. , Roh Janise M. , Ergas Isaac J. , Kwan Marilyn L. , Lee Marion , Tsai Wei-Yann , Lamerato Lois E. , Kushi Lawrence H. , Hershman Dawn L. 
Published: September 2018

e13097 Background: Use of complementary and alternative medicine (CAM) has been associated with initiation of breast cancer chemotherapy.We examined the association of CAM use with initiation of hormonal therapy in women with hormone receptor-positive (HR+) breast cancer. Methods: In aprospective cohort study designed to examine predictors of breast cancer treatment initiation and adherence, 699 women with non-metastatic stage I-III breast cancer and aged < 70 years were recruited from Kaiser Permanente Northern California during 2006-2010. Baseline interviews assessed current use of five CAM modalities (dietary supplements: vitamins/minerals, herbs/botanicals, other natural products; mind/body therapies: mind-body self-practice, mind-body practitioner-based). Based on electronic pharmacy records, hormonal therapy initiation was defined as ≥2 prescriptions of ≥30 pills of any hormonal therapy drug within 1 year after diagnosis. Multivariable logistic regression analysis examined a priori hypotheses testing whether current CAM use was associated with hormonal therapy initiation, adjusted for demographic, tumor characteristics, and cancer treatment. Results: Of the 699 participants,552 were diagnosed with HR+ breast cancer. Among the 552 women with HR+ breast cancer, 494 (89%) used at least 1 modality of CAM, 414 (76%) used dietary supplements, and 391 (71%) used mind/body therapies. Within 1 year after diagnosis, 481 (87%) participants initiated hormonal therapy. The rate of initiation was comparable between CAM users and non-users (87% vs. 86%). In multivariable analyses, baseline overall CAM use was not associated with initiation of hormonal therapy. However, vitamins/minerals users were more likely to initiate hormonal therapy compared to non-users (OR = 1.87, 95% CI: 1.04, 3.51). Conclusions: CAM use was high among early stage HR+ breast cancer patients. Overall, use of CAM was not associated with hormonal therapy initiation. Current use of vitamins/minerals was associated with higher initiation rate of hormonal chemotherapy.
Incorporation of NCCN guideline information in NGS-based cancer testing panel design.
Authors: Leamon John 
Published: September 2018

e13099 Background: NGS has revolutionized medical genomics. However, challenges remain in data analysis and interpretation due to the sheer volume of sequencing data produced. As such, optimized panel design is essential to effectively reduce data analysis burden while ensuring inclusion of critical variants. Ideally a panel should target biomarkers of clinical actionability, such as inclusion an active clinical trial or in the NCCN guideline. As information constantly evolves it is difficult if not impossible for any individual laboratory to capture and reflect real-time view in their panel design. Here we present an objective process for biomarker panel design utilizing a comprehensive database to identify key variants with clinical actionability. Methods: QIAGEN has built a bioinformatics database that comprehensively captures relevant scientific and clinical literature, curated through automated and manual processes. This database covers critical information including the NCCN guideline used by laboratories to interpret their sequencing results. We used this database to design an NGS biomarker panel focused on hotspot mutations clinically associated with clear clinical evidence in breast, lung, colon, breast/ovarian, melanoma cancers. Coverage of key variants is then compared with alternative commercial panels. Results: Comparative analysis indicated the QIAGEN panel covered substantially more relevant variants than either of the other ones. Over 100 variants are unique to the QIAGEN Panel. One such example is a point mutation in ERBB2 (S301F) which occurs in Non-Small Cell Lung Cancer (NSCLC) and is referenced in the NCCN guideline. Such finding would be missed if a sample harboring this mutation is tested with alternative panels. Conclusions: This study supports the value of utilizing comprehensive mutational databases in gene panel design. Specifically, the QIAGEN gene panel designed using this approach compared favorably against alternative commercial panels, employing fewer amplicons to provide superior coverage of variants with known actionability. These results demonstrate that optimal panel design permits improves the effectiveness and efficiency of NGS biomarker testing.
Durable complete responses observed in IDH1 mutated high grade glioma at first recurrence undergoing treatment with Toca 511 and Toca FC.
Authors: Cloughesy Timothy Francis , Ostertag Derek , Landolfi Joseph C. , Walbert Tobias , Vogelbaum Michael A. , Elder J. Bradley , Bloomfield Steven , Carter Bob , Chen Clark , Kalkanis Steven N. , Kesari Santosh , Lai Albert , Lee Ian , Liau Linda M. , Mikkelsen Tom , Nghiemphu Phioanh Leia , Piccioni David Eric , Jolly Douglas J. , Gruber Harry E. , Das Asha 
Published: September 2018

e13504 Background: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to cell division requirements for virus integration into the genome and defects in innate and adaptive immune responses found in cancers that support virus replication. Toca 511 spreads through cancer cells and stably delivers the gene for an optimized yeast cytosine deaminase that converts the prodrug Toca FC (an investigational, extended-release formulation of 5-fluorocytosine) into 5-fluorouracil (5-FU). 5-FU kills infected cancer cells that are dividing, diffuses and kills surrounding cancer cells as well as myeloid derived suppressor cells and tumor associated macrophages, thus reestablishing immunity to tumor. Methods: In this phase 1 trial (NCT01470794), ascending doses of Toca 511 were injected into the resection bed of patients with recurrent high grade glioma undergoing resection, followed by oral administration of courses of Toca FC 5-7 weeks after Toca 511 injection. Additional cohorts included combination of Toca 511 & Toca FC with bevacizumab or lomustine. Results: Objective responses (ORs) are observed in IDH1 wildtype (wt) and mutant (mt) phenotypes, including 3 complete responses (CRs) (2 IDH1 mt and 1 IDH1 wt) and 2 partial responses (2 IDH1 wt) for patients treated with Toca 511 & Toca FC, and 1 CR (1 IDH1 mt) for a patient treated with Toca 511 & Toca FC and bevacizumab. ORs are observed 6-19 months after Toca 511 injection and are consistent with an immunologic mechanism. Median time to initial response is 9.2 months; median duration of response (mDOR) is 25.2 months. Excluding the combination cohorts, mDOR is 26.7 months. All responders are alive 21.2+ to 42.6+ months, suggesting a correlation of OR and OS. An additional radiologic CR is observed in 1 IDH1 mt patient at 1st recurrence who received intravenous Toca 511 plus injection into the resection bed. All 4 IDH1 mt patients treated at 1st recurrence had CRs. Conclusions: There may be an association between ORs and IDH1 mutation with Toca 511 & Toca FC treatment. Updated clinical benefit, molecular profiles and tumor mutational load are reported. Clinical trial information: NCT01470794.
A potential role of pemetrexed (PMTX) for the treatment (Tx) of thymidylate synthase (TS) negative primary brain tumors and systemic malignancies with CNS metastasis.
Authors: Kim Lyndon J. , Evans James J , Judy Kevin D. , Farrell Christopher , Andrews David W. 
Published: September 2018

e13519 Background: Fluoropyrimidne analogue Capecitabine, a TS inhibitor, can cross blood brain barrier and has been used for the Tx of breast cancer with brain metastasis (mets). An antifolate Methotrexate (MTX), which also inhibits TS, has been used for the Tx of PCNSL secondary to it's excellent CNS penetration. MTX analogue, PMTX inhibits purine synthesis via TS and DHFR, and pyrimidine synthesis via GARFT, thus, making it a viable Tx option for CNS malignancies. Methods: We have treated 40 pts with previously heavily treated recurrent primary and systemic malignancies with CNS mets based on the molecular profiling. 26/40 pts were found to have TS negative expression (5/12 GBM, 5/5 AA, 1/1 Gr II Astrocytoma (A), 5/7 meningioma, 1/3 PCNSL, 1/2 Esthesioneuroblastoma, 1/1 chordoma, and 7/9 brain mets) and 10/26 TS negative pts were treated with PMTX. MRI was performed every 2-3 mo for tumor response. Results: Total pts: 10. M:F 6:4. Age: 48-88 yo. Median age: 61.9 yo. Tx period: 7/14–1/17. 1/1 GBM pt: stable disease (SD) x 4 mo. 1/2 AA pts: SD x 4 mo, 1/2 pts: tumor progression. 1 Gr. II A pt, SD x 7 mo. 2/2 meningioma pts: SD x 2 and 4 mo. Both pts also received concurrent cisplatin (also ERCC1 negative). 3/3 pts: squamous cell Ca of skin with skull base/brain mets responded x 24 mo, 24 mo and 3 mo respectively (1 PR and 2 SD), 2 pts: still receiving Tx. 1 pt: 26 mo reponder, died of nontumor related issue. 1/1 chordoma pt: SD x 11 mo. Toxicities: very mild except 2 pts (Gr. 3-4) who also received cisplatin. Conclusions: TS negative expression is commonly found in most of secondary malignancies with brain mets and in non-GBM primary brain tumors. PMTX appears to have a favorable efficacy for the Tx of TS negative primary and systemic malignancies with CNS mets. Albeit small cohort, overall response was 90% (PR:1, SD:8). Tx was particularly effective for squamous cell ca with brain mets and responses were durable in all spectrum. Due to favorable tolerance and response, especially in the elderly pts with squamous cell with brain mets, PMTX could be an excellent Tx option for TS negative CNS malignancies. PMTX trial for TS negative CNS malignancies should be considered.
Association of clinical phenotype and treatment history with survival in adult brainstem glioblastoma.
Authors: Nam Jooyeon , Harrison Rebecca A. , Weathers Shiao-Pei S. , Pillainayagam Clement , De Groot John Frederick , Kamiya-Matsuoka Carlos , Loghin Monica Elena , Penas-Prado Marta , Yung W. K. Alfred , Li Jing , Ferguson Sherise D. , O'Brien Barbara Jane 
Published: September 2018

e13539 Background: Brainstem gliomas are rare, comprising 1-2% of malignant primary brain tumors. Brainstem glioblastoma (bGBM) often poses a therapeutic challenge due to scarcity of evidence guiding treatment, and the high rate of neurologic morbidity. We examined bGBM cases at MD Anderson Cancer Center (MDACC) to characterize the salient clinical features of bGBM, and the impact of therapy on patient survival. Methods: Adult patients with pathologically-confirmed bGBM (N = 34) treated at MDACC between June 2005 and June 2015 were identified from the neurosurgical database. Patients’ clinical, radiographic, and treatment data were extracted from the medical record. Descriptive statistics and Kaplan-Meier analyses were performed. Results: Mean age was 52.5 years (SD = 12.1) and median KPS was 80 (SD = 14.2) at time of diagnosis. Initial surgical intervention included biopsy (82.4%) and resection (17.6%). Most patients were treated with concurrent chemoradiation (N = 18, 52.9%) or sequential radiation followed by chemotherapy (N = 8, 23.5%), and the remainder had no documented post-operative anti-tumor therapy. At the time of this analysis, 82.4% of the cohort had died. Median progression free survival (PFS) was 5.8 months (SD = 6.7) and overall survival (OS) was 8.9 months (SD = 19.6). On univariate analysis, gait abnormality (p = .02), incoordination (p = .002), dysphagia (p = .04), or facial numbness (p = .01) at presentation was associated with shorter OS. KPS of ≥70 at diagnosis was significantly associated with better OS (15.6 vs 3 months, p = .001), and the patients with good functional status were more likely to receive concurrent chemoradiation. Bevacizumab was given as concurrent or adjuvant treatment in 2 and 3 cases, respectively, and did not affect OS (p = .82). Conclusions: This retrospective analysis demonstrates a significant and complex relationship between presenting clinical features, functional status and variable treatments in bGBM and survival outcomes. This evidence contributes to our understanding of bGBM, and highlights areas for further study in this malignant condition.