bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of clinical history (CH) for Lynch syndrome (LS) risk assessment: An economic decision analysis.
Authors: Sadeghi Sarmad , Barzi Afsaneh , Kattan Michael W. , Meropol Neal J. 
Published: March 2020

1514 Background: Previous studies comparing screening strategies (STs) for LS concluded that immunohistochemistry (IHC)-based STs are most cost effective. However, these analyses generally exclude clinical history (CH)-based criteria due to concerns for reliability, e.g. Amsterdam (Ams), Bethesda (Beth), MMRpro (Mpro), MMRpredict (Mpre) and PREMM (PRE). We conducted a comprehensive comparison of all STs. Methods: Using assumptions from published reports we performed a cost effectiveness analysis (CEA) with a societal viewpoint using TreeAge software. 20 STs for proband (Pd) and general population (GP) screening in a cohort of 100,000 assumed a 3% LS prevalence (Prev) in Pd and 0.23% in GP, 5 first degree relatives (FDRs) per LS diagnosis (Dx), 50% LS Prev in FDRs, and 90% genetic testing (GT) compliance in Pds and GP and 52% in FDRs. We used the number of LS Dxs as effectiveness measure (EM). Sensitivity, accuracy, and incremental cost effectiveness ratios (ICERs) were calculated. Results: The ST of Mpro followed by GT is highly sensitive and has an accuracy of .997. Assuming 1-1.4 life years saved per Dx based on prior studies, this strategy is also cost effective. Strategies with greater sensitivity were dominated or not cost effective. Table shows results in order of increasing cost per Dx. Conclusions: This comprehensive comparison suggests that Mpro is an appropriate first step in screening for LS in Pds, and its routine use may be considered as a quality measure in the management of colorectal cancer. IHC + BRAF, GT should be reserved for Pds where CH is incomplete. [Table: see text]
PTEN germline mutations in patients first tested for other hereditary cancer syndromes: Would use of risk assessment tools have reduced health care costs?
Authors: Mester Jessica , Moore Rebekah , Eng Charis 
Published: March 2020

1516 Background: PTEN Hamartoma Tumor Syndrome (PHTS) includes patients with Cowden (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) with germline PTEN mutation. Breast, colon, endometrial cancer and GI polyposis are associated, creating overlap with Hereditary Breast and Ovarian Cancer (HBOC), Lynch (LS) and adenomatous polyposis syndromes (APS). We reviewed our PHTS patient series to find how often testing criteria for these syndromes were met or testing was pursued before PTEN. Methods: Patients were prospectively recruited by relaxed International Cowden Consortium criteria or presence of known germline PTEN mutation; mutations were identified by mutation scanning or MLPA analysis and confirmed by sequencing or quantitative PCR, respectively. Families were excluded if diagnosed with CS or BRRS before 1998, family history was unavailable, or proband was <18 yrs. Pedigree, genetic testing reports, and medical records were reviewed to determine if patients met HBOC testing criteria, Amsterdam II or Bethesda 2004 criteria, or had adenomatous polyps. Risk assessment was conducted for BRCA1/2 via the BRCAPRO, Myriad II, and Penn II models; for MLH1/MSH2/MSH6 via the PREMM1,2,6 and MMRPro models; and for PTEN via the Cleveland Clinic (CC) PTEN Risk Calculator. Results: 115 PTEN mutation-positive adult probands were identified among 3,405 patients. 53 (46.1%) met testing criteria for HBOC or LS and 34 (29.6%) underwent previous testing for HBOC, LS or APS. Average risk for BRCA1/2 and MLH1/MSH2/MSH6 mutations in tested patients were 7.5-16.9% and 33.1-41.4%, respectively; whereas PTEN mutation risks were 35.9% and 79.7%. No patient tested for APS (average PTEN mutation risk 73%) had >5 adenomas. An estimated $89,700 was spent on negative analyses for HBOC, LS and APS among patients ultimately found to have germline PTEN mutations. Conclusions: PHTS should be part of the differential diagnosis for patients referred for question of HBOC, LS or APS. Pathology review is key for patients with polyposis. Using the CC PTEN risk calculator enables clinicians to understand when PTEN mutation risk is high, allowing testing to proceed in a step-wise and cost-saving manner.
Alcohol and breast cancer risk in postmenopausal women: The PLCO experience.
Authors: Falk Roni , Maas Paige , Schairer Catherine , Buys Saundra S. , Chatterjee Nilanjan , Lee Theresa , Ziegler Regina G , Isaacs Claudine 
Published: March 2020

1521 Background: Moderate alcohol consumption is an established breast cancer (BC) risk factor. Invasive BC is a heterogeneous disease comprised of several histological subtypes with distinct biological features that suggest etiologic differences. Several studies show the alcohol link may be stronger for estrogen receptor-positive tumors (ER+/PR+ and ER+/PR-) and for lobular BC. Few have evaluated the role of alcohol consumption by BC histology and hormone receptor status combined. Methods: We evaluated the risk of BC by baseline alcohol consumption in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort (54649 participants, 1786 incident invasive breast cancers) by histology and hormone receptor status. Histologic subtype-specific associations were evaluated using a recently developed Cox proportional hazards model to calculate multivariate hazards ratios (HR) and 95% confidence intervals (CI). Results: 1444 ductal (81%), 233 lobular (13%) and 109 mixed ductal lobular (6%) cases were identified. The majority were ER+/PR+ (ductal: 959 ER+/PR+, 136 ER+/PR-, 229 ER-/PR-; lobular: 179 ER+/PR+, 37 ER+/PR-, 6 ER-/PR-; mixed ductal/lobular: 88 ER+/PR+, 6 ER+/PR-, 5 ER-/PR-). For ductal and lobular BC, risks for alcohol consumption were modestly elevated; compared to never drinkers, women consuming 7-14 drinks/week had a 40% increase in HR in both histologic subtypes. Risks for mixed ductal lobular cancer were significantly higher, particularly for women consuming 7-14 drinks per week (HR=3.0; 95% CI=1.5, 6.1). For all histologies combined, alcohol risks were confined to ER+/PR+ cancers with HR=1. 6 (95% CI=1.3, 2.1) for women consuming 7-14 drinks/ week; p trend=0.0005. Similarly, for each histologic subtype, the risk for alcohol consumption was limited to ER+/PR+ tumors, and notably, very few cases with pure lobular or mixed ductal lobular cancer were either ER+/PR- or ER-/PR-. Conclusions: Moderate alcohol consumption is associated with risk of ER+/PR+ BC in each of the predominant histologic subtypes, but not with hormone receptor-negative cancer. Unlike other studies, we did not find a link between alcohol consumption and ER+/PR- BC.
Cancer screening in France: 3rd edition of the EDIFICE survey.
Authors: Viguier Jérôme , Eisinger Francois , Coscas Yvan , Morere Jean F. , Blay Jean-Yves , Roussel Claire , Pivot Xavier B. 
Published: March 2020

1568 Background: The EDIFICE survey program started in 2005 and was aimed at providing a better understanding of the participation of the French population in cancer screening programs and assess the evolution over time. The EDIFICE 3 survey was conducted in 2011, following EDIFICE 1 (2005) and EDIFICE 2 (2008), and focused on colorectal, breast and prostate cancer. Methods: This third nationwide observational study, EDIFICE 3, was conducted by phone interviews among a representative sample of 1603 subjects aged between 40 and 75 years, using the quota method. The analysis focused on the target population of the national screening programs for breast and colorectal cancer (50-74 years). The same population was analysed for prostate cancer screening behaviours. Results: For breast cancer, the rate of women attending at least one screening test was 93%/94%/95% in 2005/2008/2011 respectively. A mammography had been performed as recommended within the last two years for 75%/83%/83% among them. We observed an increase in timing compliance between 2005 and 2011, significant for women aged 65-74. For colorectal cancer, the rate of subjects attending at least one screening test was 25%/38%/59%. A fecal test or colonoscopy had been performed according to the recommended timing for NA/30%/51% among them. Colorectal cancer screening has increased significantly in all age groups, especially between 65 and 69 years, and for both genders. For prostate cancer, the rate of men having performed at least one screening test (PSA and/or rectal examination) was 36%/49%/50%.This rate have significantly decreased in men aged 50-59 between 2008 and 2011(44% vs 37%, p<0.05). Conclusions: For National Programs, the attendance rate remains high for breast cancer screening and is improving for colorectal cancer screening. However, the European guideline objective rate of participation for colorectal cancer screening has not yet been reached. Despite the absence of recommendations, prostate cancer screening is frequently carried out and stable overall.
Association of a history of autoimmunity or hypersensitivity with overall survival in breast cancer.
Authors: Olsson Hakan Lars , Kogler Ulrika , Einefors Rickard , Ellberg Carolina 
Published: March 2020

1594 Background: Antibody therapy of malignant melanoma with ipilimumab is associated with the development of an autoimmune disease. The aim was to investigate if preexisting autoimmune disorders or hypersensitivities, similar to the side effects of immunotherapy in malignant melanoma, gave a better overall survival for breast cancer (BC) patients, compared with patients without these disorders. Methods: A consecutive clinical material consisting of 1,705 breast cancer patients diagnosed between 1980 and 2010 was used. The patients were grouped according to preexisting autoimmune disease or hypersensitivities. The remaining BC patients were used as a reference group. All analyses were adjusted for age at diagnosis, T, N, M-status of the tumor, and ever-use of HRT simultaneously. A p value of less than 0.05 was considered significant. Results: One hundred and twenty-five (7.3%) patients had a history of autoimmunity and 72 (4.2%) patients had a history of hypersensitivity prior to BC diagnosis. Our main finding was that BC patients with a preexisting autoimmune disease or hypersensitivities with ER-negative tumors had a longer overall survival compared to patients without, HR 0.55, 95% CI 0.31-0.97. The risk was specifically low in BC patients with hypersensitivity and ER-negative tumors, HR 0.39, 95% CI 0.16-0.96. The risk was nonsignificantly lower in the autoimmune group, HR 0.78, 95% CI 0.37-1.61. Stratifying both on ER-status and menopausal status, similar results were seen in premenopausal BC patients with hypersensitivity. Postmenopausal BC patients with an ER-negative tumor and an autoimmune disease had a longer nonsignificant overall survival, HR 0.3, 95% CI 0.07-1.26. Conclusions: BC patients with an ER-negative tumor and/or diagnosed before menopause had a longer overall survival when previously diagnosed with hypersensitivity. For BC patients with an autoimmune disease, the prognostic benefit was seen when diagnosed postmenopausally with an ER-negative BC. Preexisting or induced autoimmunity or hypersensitivity may prolong life in breast cancer especially in young patients and those with ER-negative tumors.
Long-term survival and prognostic factors in neuroendocrine tumors: Results from a large multicenter study.
Authors: Faggiano Antongiulio , Grimaldi Franco , Manzoni Marco , Davi Maria Vittoria , Ferone Diego , Giuffrida Dario , Roiter Ignazio , Fanciulli Giuseppe , Papini Enrico , Martini Chiara , Franchi Giulia Maria , Fasola Giampiero , Albertelli Manuela , Crinò Lucio , Colao Annamaria , Ferolla Piero 
Published: March 2020

1604 Background: The clinical behavior of neuroendocrine tumors (NET) is highly variable, but the only data available in literature on large series are mainly based on retrospective register data collected in 3-5 decades, focusing on short-term follow-up. These are clearly insufficient due to the frequent evolution in classification criteria, diagnostic techniques and the scarcity of clinical data. Methods: Data from a total of 1659 NET patient were collected from 12 Italian referral centers. A specific software was developed for the study. Only patients with histological diagnosis revised according to the WHO Classification in active long term follow-up in the period 1990-2010 were included in the study. Patients with incomplete diagnostic work-up, without clinical data or lost at follow-up were excluded. Cumulative survival were analyzed according to site of origin, histotype, grading, ki67 score, secreting pattern (functioning or not functioning) and staging. Results: At 2 yr cumulative survival do not differ between pancreatic (pNET 94.9%), gastrointestinal (GINET 94.4%) and lung NET (TNET 94.6%), functioning (93.5 %) and non functioning (93.9%), while was significantly different between T1N0M0 (98%), T1N1M0 (92.9%), T1N1M1 (90.2%) and grading (G1 98%, G2 96.8%, G3 84.1%). At 5, 10 and 15 yr, cumulative survival were respectively 90.9, 77.1, 62.7% for pNET, 88.7, 83.5, 62.7% for GINET 90.3, 80.2, 67.9% for TNET. 88.4, 77.0, 59.0% in functioning and 89.8, 79.1, 64.6% in not functioning. 96.1, 89.5 and 77.0% for T1N0M0, 88.2, 83.5, 70.4 for T1N1M0 and 82.0, 55.8 and 43.9 for T1N1M1, 93.1, 82.3, 75.4% for G1, 87.8, 64.8, 48.6% for G2, 81.4, 75.2, 40.1% for G3. Conclusions: Brief (2y) and very long term (15y) survival do not significantly differ between different site of NET origin. Functioning tumors have the same survival rate at 2 y but lower at 15 y. Staging and grading appear as the most significant prognostic factors particularly at 10 and 15 y. Long-term cumulative survival in NET results significantly higher than in historical series, probably due to the anticipation of the diagnosis and the availability of new therapeutic strategies.
Survival of elderly Medicare patients after standard chemotherapy for advanced lung and gastrointestinal cancers in the real world.
Authors: Lamont Elizabeth B. , He Yulei , Lan Lan , Joffe Steven 
Published: March 2020

1605 Background: Elderly cancer patients are under-represented on clinical trials that determine standards of treatment, thus survival of such patients following standard treatment in the real world is not known. We describe unadjusted survivals for site, stage, and treatment-specific cohorts of elderly Medicare cancer patients who were treated in usual care settings. Methods: From SEER-Medicare data, we identified elderly Medicare patients with advanced lung or GI cancers who received specific standard chemotherapy regimens within six months of diagnosis. Of the 108,386 patients with the cancer sites and stages of interest, 39% (42,570/108,386) received some form of chemotherapy within six months of diagnosis. Only 32% (13,689/42,570) received one of the specific standard regimens we studied. Results: Median survival times and interquartile ranges (IQRs) varied according to cancer site, stage, and treatment. For 598 stage IV CRC patients on FOLFOX, the median survival was 19.4 mos (IQR 9.3-43.0); this is comparable to PRIME Study patients (19.7 mos). For 130 stage IV CRC patients on FOLFIRI, the median survival was 16.1 mos (IQR 5.6-30.0), which is lower than BICC-C Study patients (23.1 mos). For 3,815 advanced pancreatic cancer patients on gemcitabine, the median survival was 4.3 mos (IQR 2.0-8.7), which is slightly lower than CALGB 80303 patients (5.8 mos). For 8,040 stage IV NSC lung cancer patients on carboplatin and paclitaxel, the median survival was 7.0 mos (IQR 3.2-14.2); this is comparable to ECOG 1594 patients (7.8 mos). For 1,104 extensive stage SCLC patients on cisplatin and VP16, the median survival was 8.5 mos (IQR 4.7-12.9), which is slightly lower than CALGB 9732 patients (10.0 mos). Conclusions: The observed survival of cancer site, stage, and treatment-specific cohorts of elderly Medicare patients with advanced lung or GI cancers who were treated in real world settings with standard chemotherapy was, in general, similar to that of patients treated with nominally identical regimens on trials. Further analyses should explore the shorter survival for elderly Medicare patients with stage IV CRC treated with FOLFIRI in the usual care setting compared to patients treated on trials.
Impact of obesity and overweight in the prognosis of women diagnosed with non metastatic breast cancer in a Mexican cohort.
Authors: Aguilar José Luis , Martinez Itzel Anahi , Villarreal-Garza Cynthia Mayte , Lara Gisell Anaid , Medina Fernando Lara , Alvarado Miranda Alberto , De La Garza Jaime G. , Mohar Alejandro , Meneses Abelardo , Herrera Gomez Angel , Olvera-Caraza Daniela , Granados-Garcia Martin , Arrieta Oscar 
Published: March 2020

1607 Background: Mexico positions right up at the top with U.S. in worldwide rankings of the most obese countries. In addition, breast cancer (BrCa) is the main type of cancer among women in this country. Studies have shown inconsistent results regarding obesity as a prognostic factor for worse outcome. Methods: Our aim is to identify if overweight and obesity confer poor prognosis in non-metastasic BrCa patients (pts). We identified 1799 Hispanic women with newly diagnosed BrCa who attended the National Cancer Institute in Mexico from 2004-2008 and compared clinical and pathological features and overall survival (OS) between pts with a body mass index (BMI) > or ≤ than 25. Results: The median age at diagnosis was 51 years. A BMI>25 was found in 71% of pts. Postmenopausal women comprised 52%, and had a greater proportion of cases with a BMI>25 than premenopausal pts (75% vs. 67%, p<0.0001). Pts with BMI>25 presented with more advanced TNM stages and nodal involvement than their counterparts (73% vs. 67%, p=0.005 and 76% vs. 71%, p=0.017; respectively). Overall prevalence of hormone-receptor (HR), triple-negative (TN) and HER2 positive disease was 62%, 23%, and 27%, respectively. Differences according to receptor status between pre and postmenopausal pts and BMI are shown in table. There was no difference in disease-free survival and OS according to overweight and obesity in the overall population, but when menopausal status was considered, premenopausal pts with BMI>25 had a worse OS compared to pts with BMI<25 (HR 1.6, p=0.037). This difference was not seen in the postmenopausal group. Conclusions: Obesity may influence BrCa outcomes via several hormonal and inflammatory mechanisms. In this study, overweight and obesity confer a poor prognosis in premenopausal patients, possibly related to excess estrogen availability and higher prevalence of TN BrCa. Therefore, overweight and obesity deserve additional attention to assess possible causal relationships that potentially could be modified to improve outcomes in premenopausal patients. [Table: see text]
Bevacizumab for recurrent WHO grade III anaplastic glioma (AG).
Authors: Delios Anna Maria , Brennan Cameron W , Huse Jason T. , Colevas Kara , Omuro Antonio Marcilio Padula 
Published: March 2020

2028 Background: Salvage treatment with bevacizumab (BEV) has been increasingly used in grade III AG, but limited data are available, with conflicting results reported. Because of differences in molecular characteristics, angiogenesis mechanisms, growth rate and chemosensitivity, results observed in glioblastoma (GBM) treated with BEV may not apply to AG, and may differ between anaplastic astrocytomas (AA) and oligodendrogliomas (AO). Methods: IRB approved retrospective review of all pts with recurrent WHO grade III AG treated with BEV at MSKCC. Response and progression were determined by RANO criteria. Results: BEV was given to 39 pts with recurrent grade III AG (AA: 26; AO: 10; anaplastic oligoastrocytoma [AOA]: 3); median (med) age: 49 (range 20-75); med KPS: 80 (60-100). MGMT promoter methylation was determined in 17 pts (methylated 8, unmethylated 9). Amongst AO/AOA, 1p/19q co-deletion was present in 6 and absent in 5. IDH1/ IDH2 mutations were present in 3/5 tested tumors. Med time from diagnosis of AG to BEV treatment was 11.5m (3 – 112.5). The med number of previous recurrences was 1 (range 1-4). BEV was given as single agent to 16 pts and combined with a cytotoxic agent in 23. Objective response rate (ORR) was 41% (complete response: 5; partial: 11). The med progression-free survival (PFS) was 4.8m (6-m PFS: 35% [95% CI 20-50]). The med overall survival (OS) was 11.5 m (1y-OS: 45% [95% CI 29-61]). In pts achieving ORR, med OS was 13 m vs 4 m in pts with stable/progressive disease (P=0.02). Pts at first recurrence fared better than pts with more than one recurrence (med PFS: 6 vs 3.4 months, P=0.04). AO/AOA tended to fare worse than AA (med PFS 3 vs 5.5 m, P=0.07). There were no differences in PFS (P=0.8) or OS (P=0.4) between single agent vs BEV + cytotoxic agent. Toxicity included one grade 4 brain hemorrhage. Conclusions: In this relatively large series, BEV was associated with higher ORR and PFS as compared to historical controls, although improvements in those endpoints were of a lower magnitude than in GBM. While ORR predicted OS, improvements in OS were not apparent; results in AO were particularly disappointing. The use of BEV in this population requires reappraisal in a randomized study with adequate stratification for histology and number of previous recurrences.
Association of breast cancer in men with exposure to 5-α reductase inhibitors: A RADAR report.
Authors: Belknap Steven M , Godinez-Puig Victoria , Brannigan Robert E , Lin Simon M , Cashy John , Chowdhary Rajesh , Postelnick Michael J , Fotis Michael A , Irwig Michael , Khan Seema Ahsan , Gradishar William John , Garg Vishvas , Shen Xian , Raisch Dennis W , Nardone Beatrice , Rosen Steven T. , Edwards Beatrice J. , McKoy June M , Yarnold Paul R , West Dennis P. 
Published: March 2020

2532 Background: Breast cancers in men (BCM) account for <1% of all breast cancers. Dihydrotestosterone (DHT) inhibits proliferation of normal and neoplastic mammary tissue and constrains the effect of estrogens. Finasteride (F) and dutasteride (D) are 5-α reductase inhibitors (5-αRIs) that reduce systemic and local dihydrotestosterone and cause gynecomastia in 1–3% of men. The package inserts for F and D state, “the relationship between long-term use of (finasteride/dutasteride) and male breast neoplasia is currently unknown.” F and D are marketed for treatment of symptomatic benign-prostatic hyperplasia. F is marketed for treatment of androgenetic alopecia. Methods: To detect disproportionality in the FDA MedWatch dataset, we calculated the empiric Bayes geometric mean (EBGM) for association of BCM with F or D. We also calculated the attributable risk of BCM exposed to F or D among men at an urban academic hospital (Northwestern Memorial Hospital) and at a rural healthcare system (Marshfield Clinic). Results: In the MedWatch dataset, we identified 33 reports of F-associated BCM and 5 reports of D-associated BCM. For F–associated BCM, the EBGM was 58.95 (95% CI 24.47-81.76; p=0.0001). For D-associated BCM, the EBGM was 15.79 (95% CI 4.57-35.49; p=0.0001). The mean age for BCM after 5-αRI exposure was 70±11 years; 11/38 (29%) had gynecomastia. There were 38 cases of BCM associated with 5-αRI in the combined Northwestern and Marshfield cohort (see table below). Conclusions: We found a highly significant association between BCM and 5-αRI exposure in each of 6 separate analyses (3 sources X 2 drugs), with an estimated 1 extra BCM per 564 men exposed to 5-αRIs. We now plan to assess BRCA status and other risk factors. Given that 5-αRIs are marketed for control of lower urinary tract symptoms or for cosmetic purposes, it is not immediately obvious that use of finasteride or dutasteride for their labeled indications would provide any net benefit. [Table: see text]