bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of sentinel node biopsy in patients with locally advanced breast cancer after neoadjuvant therapy: A pilot study.
Authors: Tibau Martorell Ariadna , Duch Joan , Quintana Maria Jesus , Lopez Vilaro Laura , Ojeda Belen , Alonso M Carmen , Ramon y Cajal Teresa , Lerma Enrique , Moral Antonio , Capdevila Enric , Pineda Rosa , Sabate Josep Maria , Estorch Montserrat , Barnadas Agust 
Published: March 2020

1120 Background: Sentinel lymph node biopsy (SLNB) is a widely used staging method for patients with early breast cancer. Neoadjuvant Therapy (NT) modifies the anatomical conditions in the breast and axilla, and thus reliability of SLNB after NT remains controversial. The aim of this study is to prospectively evaluate the feasibility and accuracy of this procedure in this particular group of patients. Methods: Between December 2007-2011, 69 patients (mean age 56 years) with locally advanced breast cancer (LABC) were prospectively studied. Patients were T1-4, N0-1, M0. Prior to surgery, 61 patients received chemotherapy (CT) (adryamicin/cyclophosphamide followed by docetaxel) and 8 patients endocrine therapy (ET). Thirty nine patients were initially node-negative (cN0) and 30 patients had clinical/ultrasound node-positive confirmed by cytology (cN1) at presentation. All patients were clinical and ultrasound node-negative after NT. The study contained two groups of patients: group A (validation) included the first 29, associated with an axillary lymph node dissection (ALND) after NT, in order to validate the study, and group B included the last 40, only associated with an ALND when SLNB was positive or not found. Results: Whole SLNB identification rate was 89.9%, and no significant differences were found between patients initially cN0 (92%; 36/39) and initially cN1 (87%; 26/30). Four of 7 patients in whom SLNB was not found had residual nodal metastasis after NT (3 of them were initially cN1). Sentinel lymph nodes were successfully identified in 87% (7/8) of patients after ET and in 90% (55/61) of patients after CT. There was one false negative (FN) case after CT in group A (9% of overall false negative rate, initially cN0) and there were no FN cases after ET. Positive SLNB were higher in initially cN1 group (53%; 16/30) than in initially cN0 group (18%; 7/39). Conclusions: SLNB after NT (CT or ET) is safe and feasible in patients with LABC, not only in initially cN0 but also in initially cN1. It accurately predicts the status of the axilla and avoids unnecessary ALND.
Association of pathologic complete response following neoadjuvant chemotherapy with survival among young women with breast cancer.
Authors: Greenup Rachel Adams , Bardia Aditya , Buckley Julliette M , Niemierko Andrzej , Camp Melissa , Coopey Suzanne , Gadd Michele , Schapira Lidia , Taghian Alphonse G. , Smith Barbara L. , Specht Michelle Connolly 
Published: March 2020

1122 Background: Neoadjuvant chemotherapy is increasingly being used in the treatment of breast cancer, yet data on efficacy and significance of pathologic complete response (pCR) is limited among young women. We sought to determine whether timing of chemotherapy impacted disease-free (DFS) or overall survival (OS), and whether pCR is associated with improved prognosis among young women with breast cancer. Methods: We performed an IRB-approved review of women ≤40 years old who received treatment for stage I-III breast cancer during 1996-2008 at our institution. DFS and OS were determined through use of state tumor registry, death certificate data, and Social Security Master Death Index. Tumor biology was categorized as hormone receptor positive (HR+), HER-2+, or triple negative (TN) breast cancer. pCR was defined as lack of invasive cancer in the breast and axilla on final pathologic review. Cox regression analyses were conducted to evaluate the hazard ratios (HRs) of the association between chemotherapy and outcomes. Results: 370 women ≤40 years old (median age = 36.5, range: 22-40) were treated with systemic therapy for stage I-III breast cancer. 54.7% of tumors were HR+, 20.9% were HER-2+, and 24.4% were TN. After adjusting for stage, there was no difference in DFS or OS among women who received neoadjuvant versus adjuvant chemotherapy (p=0.6 and 0.5 respectively). pCR following neoadjuvant chemotherapy was higher among HER-2+ (50%) and TN (28.6%) tumors when compared to HR+ tumors (17.6%). Among women who received neoadjuvant chemotherapy, 10-year DFS and OS rates were significantly higher when pCR was achieved when compared to lack of pCR (HR=0.20, p value=0.01 and HR=0.13, p=0.05). pCR with neoadjuvant chemotherapy trended towards higher 10-year DFS and OS when compared to women who received adjuvant chemotherapy (HR=0.30, p value=0.08 and HR=0.20, p=0.1). Conclusions: pCR after neo-adjuvant chemotherapy is associated with improved disease-free and overall survival in young women with breast cancer. Pathologic complete response may be a valuable surrogate marker for survival, and aid in the evaluation of therapeutic efficacy in young breast cancer patients.
Breast cancer surgery during pregnancy.
Authors: Surapaneni Rakesh , Jozefara Jolanta , Hendershott Karen , Hunter Krystal , Cardonick Elyce 
Published: March 2020

1127 Background: There is limited literature on breast surgery during pregnancy. We present prospective registry data on 88 breast cancer patients who underwent breast cancer surgery during pregnancy. Methods: The Cancer and Pregnancy Registry is a voluntary international registry that prospectively collects the clinical course, treatment, and disease outcome of women diagnosed with cancer during pregnancy and the perinatal and neonatal outcomes of their children. Results: We identified 88 patients who were diagnosed with breast cancer and had surgery while pregnant. 59 patients (67%) underwent Mastectomy while29 patients (32%) underwent breast conserving surgery (BCS). Out of 43 patients who underwent BCS as their first surgery 13 patients (30.23%) required subsequent mastectomy during pregnancy. 15 patients (34.88%) from the BCS group and 4 patients (8.69%) from the Mastectomy group had positive margins. There was no significant difference between patients who underwent mastectomy vs BCS based on Age (34.67 vs 34.72 P: 0.97), gestational age at surgery (14.05 vs 16.06 P: 0.23) or ER positivity (47.5% vs 46.4% P: 0.93). 2 patients had neo-adjuvant chemotherapy. 17 patients (19.31%) had sentinel lymph node biopsy. 37 patients (42%) had a pregnancy complication. There was no difference in the rate of complication based on mastectomy vs BCS(45.8% vs 34.5% P: 0.31). There was only 1 patient (from mastectomy group) that delivered within 2 weeks of surgery. Of the 17 patients (19.3%) with spontaneous preterm delivery, there was no difference between Mastectomy and BCS group (22% vs 13.2% P: 0.41). Of the 25 patients (28.4%) with birth complications, there was no significant difference between mastectomy vs BCS (30.5% vs 24.1% P: 0.53). There was also no difference in mean birth weight between the groups (2598 grams vs 2672.3 grams P: 0.57). Conclusions: The data supports the safety of breast cancer surgery during pregnancy. In addition, there were no identified adverse effects in patients who underwent BCS as opposed to mastectomy. Of note, only 19% of patients underwent sentinel node biopsy which is considered the standard of care in early breast cancer patients regardless of pregnancy status.
Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric cancer patients.
Authors: Walker Dana Marie , Li Yimei , Huang Yuan-Shung , Seif Alix Eden , Kavcic Marko , Torp Kari , Fisher Brian , Aplenc Richard 
Published: March 2020

1504 Background: Dexrazoxane (DXZ) is an effective cardioprotectant in children with leukemia and solid tumors. However, the potential risk of secondary acute myeloid leukemia (AML) limits DXZ use. We compared the incidence of secondary AML in pediatric cancer patients with and without DXZ exposure to estimate the risk of DXZ-associated secondary AML. Methods: We conducted a retrospective cohort study of anthracycline exposed pediatric cancer patients (excluding de novo AML) hospitalized from January 1999 to March 2011 in 43 freestanding children’s hospitals in the Pediatric Health Information System (PHIS) database. Secondary AML was defined as an ICD9 code for AML that occurred at least 90 days after first anthracycline exposure. Proportions of patients with secondary AML were compared between patients with and without an exposure to DXZ after the initial anthracycline exposure. Results: During the study period of interest, 15,532 pediatric cancer patients were exposed to anthracycline, of which 1404 (9.04%) subsequently received DXZ. Secondary AML was identified in 235 (1.51%) patients. Patients ≥ 10 years of age, black patients, patients in New England and the Midatlantic regions, and those with bone tumors were significantly more likely to have received DXZ. The unadjusted incidence of secondary AML in the DXZ exposed and unexposed patients did not differ significantly (1.21% v. 1.54%, p=0.3308). After adjusting for these variations in demographics, the incidence of secondary AML still did not significantly differ between DXZ exposed and unexposed patients (p=0.6224). Conclusions: Our findings suggest that DXZ exposure does not lead to an increased risk of secondary AML in children. These data are important given the conflicting results from individual clinical trials about the risk of DXZ-associated secondary AML. While subject to well-known limitations of administrative database analyses, these data represent the largest cohort of DXZ exposed patients with available data on the occurrence of secondary AML. Additional multivariate analyses of chemotherapeutic covariates and time to secondary AML are ongoing.
Sensitivity of clinical BRCA1 testing compared with linkage analysis.
Authors: Shah Payal D. , Garber Judy Ellen , Stopfer Jill , Powers Jacquelyn , Nathanson Katherine L. , Domchek Susan M. 
Published: March 2020

1506 Background: Specific clinical interventions in BRCA mutation carriers reduces the risk of breast and ovarian cancers and may improve survival; thus,identification of mutation carriers is important. The sensitivity of current BRCA mutation testing is unclear as a “gold standard” test is lacking. We assessed the BRCA1 mutation detection rate with current comprehensive clinical testing using linkage analysis as the comparator. Methods: 26 families with linkage analyses results available were included in this analysis. BRCAPRO, BOADICEA, and other risk estimation models were applied. Maximum-likelihood linkage analyses were performed to compute two-point and multipoint LOD scores using previously described BRCA1 –linked genetic markers; scores were classified as linked, not linked, or suggestive. At least one individual from each family underwent comprehensive testing. Results: Of 26 families analyzed, 9 demonstrated linkage and 4 demonstrated suggestive linkage to BRCA1. Of these 13 families, 12 were found to have BRCA1 mutations: a detection rate of 92.3%. In 3 of these 12 families, genetic mutation testing performed prior to large genomic rearrangement (LGR) testing was negative, demonstrating an improved detection rate with LGR testing which in this series was 23%. The 12 families with higher LOD scores and positive mutation testing had high mean prior probabilities by all models. Families which were not linked and who tested negative for mutations had lower mean prior probabilities. In one family, disease demonstrated linkage with a two-point LOD score of 1.59 and multipoint LOD of 0.85 and all risk estimation models yielded high prior probabilities. Despite this, mutation testing was negative by full sequencing and MLPA analysis. Conclusions: When evaluated in a sample of families from high-risk clinics, current comprehensive testing compares well to linkage data. The inclusion of LGR testing has improved the mutation detection capability of clinical testing; however, some mutations may still be missed. Negative mutation testing results should be interpreted in the context of family history and prior probability during counseling. Despite recent advances, further improvements in genetic testing are warranted.
Use of PTEN protein dosage to predict for underlying germ-line PTEN mutations among patients presenting with thyroid cancer and Cowden-like phenotypes.
Authors: Ngeow Joanne Y. Y. , He Xin , Mester Jessica , Radhakrishnan Deepa , Lei Junying , Romigh Todd , Milas Mira , Eng Charis 
Published: March 2020

1508 Background: Thyroid cancer is a major component of Cowden Syndrome (CS), a heritable syndrome characterized also by breast, uterine and kidney cancers. CS patients with an underlying germline PTEN mutation have a 70-fold increased risk of developing epithelial thyroid cancer. In contrast, <1% of sporadic epithelial thyroid cancer harbor a germline PTEN mutation. Thus, cost-efficient markers capable of shortlisting thyroid cancers for CS genetic testing would be clinically useful. Here, we analyzed the relationship of patient PTEN protein levels in predicting the presence of germline PTEN mutations. Methods: We conducted a 5-year, multi-center prospective study of 2792 CS and CS-like patients, all of whom had comprehensive PTEN analysis done. Analysis of PTEN and downstream proteins by immunoblotting was performed on total protein lysates from patient-derived lymphoblast lines. We compared PTEN protein expression levels between patients with pathogenic PTEN mutations (PTENmut+), and those with variants of unknown significance (VUS) or wildtype PTEN. PTEN immunohistochemistry (IHC) was performed on available thyroid samples. Results: Of 2792 CS/CS-like patients, 722 had thyroid cancer. PTEN germline pathogenic mutations were present in 36/722 (5%) patients. PTENmut+ cases presented at an earlier age (35 vs 42 years; p=0.02). PTEN frameshift and truncation mutations accounted for 55% of mutations. 95% (19/20) of PTENmut+ patients had blood-PTEN protein levels in the lowest quartile as compared to 27% (90/330) of PTEN wildtype/PTEN VUS patients (p<0.001). Low blood-PTEN levels predicted for PTENmut+ cases with a 99.6 % NPV (95%CI 97.7- 99.9) and a positive test likelihood ratio of 3.5 (95%CI 2.8-4.3). Affected thyroid tissues (n=22) from PTENmut+ cases showed loss of PTEN protein by IHC, correlating with patient blood PTEN levels (r2=0.30, p=0.016). Conclusions: Our study shows that PTEN protein dosage could serve as a molecular correlate predicting for germline PTEN mutation in CS and CS-like presentations of thyroid cancer. The clinical utility of PTEN IHC in identifying thyroid cancer patients for germline PTEN testing should be further explored.
Meta-analysis of cancer risk among users of insulin glargine.
Authors: Koechlin Alice , Boniol Mathieu , Robertson Chris , Bolli Geremia , Rosenstock Julio , Boyle Peter 
Published: March 2020

1510 Background: The association between diabetes, its risk factors and treatments, and cancer risk and death is now high on the clinical and research agenda. Methods: All data regarding cancer risk and use of insulin glargine has been assembled and meta-analyses performed using state-of-the-art statistical methodology. Glargine is the most studied insulin in this regard. A random effects model was employed with tests for heterogeneity (I2) and publication bias. These meta-analyses are based on reports from epidemiological studies involving a total of 907,008 diabetic subjects and 2,597,602 person-years of observation. Results: Based on independent estimates from 14 studies, the Summary Relative Risk (SRR) for all forms of cancer was (SRR=0.90, 95% CI (0.82, 0.98)) and for breast cancer SRR=1.14 (95% CI (1.00, 1.29)). For new users of glargine, from 7 studies, the SRR for breast cancer was SRR=1.20 (95% CI (0.90, 1.58)). Based on independent estimates for 9 studies, for colorectal cancer the SRR was 0.73 (95% CI (0.59, 0.91)) and for prostate cancer SRR=1.16 (95% CI (1.03, 1.30)). Overall, the risk of developing cancer among users of insulin glargine is reduced compared to the risk of users of other insulins. Similarly, the risk of colorectal cancer is reduced among users of glargine. While above unity, the risks of breast cancer and prostate cancer are increased marginally. Potential limitations to this meta-analysis include that the comparison group was not the same in all studies but this could also be seen as a strength. This is not likely to invalidate the findings of this analysis nor would the fact that different adjustments were made in the individual studies. Conclusions: The current evidence gives no support to the hypothesis that insulin glargine is associated with an increased risk of cancer as compared to other insulins and should give reassurance to physicians and their patients. Given the short exposure time possible to glargine (less than 5 years maximum), it is not biologically plausible to have a causal link to common forms of cancer.
Next-generation sequencing to identify candidate gene for hereditary mixed polyposis syndrome.
Authors: Gornick Michele Caroline , Li Jun , Xu Jishu , Gruber Stephen B. 
Published: March 2020

1515 Background: Rare monogenic disorders are often due to mutations that are highly penetrant, extremely rare, and strongly disrupt normal biology. Hereditary mixed polyposis syndrome (HMPS, OMIM ID %601228), is characterized by a mixture of atypical juvenile polyps, hyperplasic polyps, sessile serrated adenomas and an increased risk of colorectal cancer. Polyps appear to be inherited in an autosomal dominant fashion. The putative susceptibility locus initially mapped to 15q13-14, however, the genetic basis of this syndrome is not well understood, and no mutation or associated variants have been identified. Methods: Germline DNA from four individuals from a family with clinically and pathologically confirmed HMPS was subjected to massively parallel sequencing (Illumina GAII). Affected individuals had an average of 30x coverage of their exome and 10x coverage of their genome. Sequence calls were filtered using the criteria of ≥ 4x coverage, quality score over depth ≤ 50, depth of coverage ≤ 360, allele balance ≤ 0.75, number or MAPQ zero reads at locus < 4. Common variants were filtered out by excluding variants found in dbSNP (build131), 1000 Genomes Project, the Exome Variant Server or 80 unaffected controls sequenced by hybrid capture and whole exome sequencing. Polyphen2 and SIFT were used to predict pathogenicity of the novel, shared variants, and validated by Sanger sequencing. Expression levels of novel variants were examined in available tumor samples using qRT-PCR. Results: From the 32 previously unidentified nonsense, missense or splice site variants shared by the family members whose whole genomes were sequenced, only 5 (4 missense, 1 nonsense) were predicted to be damaging, leading to a small subset of novel candidate genes including ZNF426, which may be responsible for HMPS within this family. Conclusions: HMPS extremely difficult to accurately diagnosis and the genetic basis is unknown. Using next-generation sequencing we were able to detect previously unidentified low frequency allelic variants including a novel candidate locus.
Cost-effectiveness of the 21-gene recurrence score assay in the setting of multifactorial decision making for chemotherapy in early-stage breast cancer.
Authors: Reed Shelby D. , Dinan Michaela A , Schulman Kevin A. , Lyman Gary H. 
Published: March 2020

1525 Background: The objective of this study was to incorporate evidence from two recently-published studies to reevaluate the cost-effectiveness of the 21-gene Recurrence Score (RS) assay (Oncotype DX) in the context of multifactorial decision making to guide the use of chemotherapy for node-negative, estrogen receptor–positive breast cancer in the United States from the societal and healthcare system perspectives. Methods: We developed a decision-analytic model to first cross-classify hypothetical patients by clinicopathologic characteristics according to the Adjuvant! using risk groups and RS risk groups. We generated estimates of long-term costs, survival, and quality-adjusted survival for the RS-guided and non–RS-guided strategies using a probabilistic state transition model. In addition to costs for the 21-gene assay, we assigned attributable costs for chemotherapy, hormonal therapy, monitoring for disease recurrence, and distant recurrence. For the societal perspective, we also considered incremental patient time costs. Costs and survival were discounted at 3% annually. Results: With the RS-guided strategy, 40.4% of patients were expected to receive chemotherapy relative to 47.3% in the non–RS-guided strategy. Targeted use of chemotherapy in the RS-guided strategy was expected to increase survival by 0.19 years (95% CI, 0.09 to 0.32) and 0.16 QALYs (95% CI, 0.08 to 0.28). Lifetime direct medical costs were expected to be $2692 (95% CI, 1546 to 3821) higher with the RS-guided strategy. The incremental cost-effectiveness ratios (ICERs) were $14,059 per life-year saved (95% CI, $6840-$28,912) and $16,677 per QALY (95% CI, $7613-$37,219). When incorporating lower indirect costs of $950 per patient, the ICERs were $9095 per life-year saved (95% CI, dominant-$23,397) and $10,788 per QALY (95% CI, $6840-$30,265). In probabilistic sensitivity analysis, more than 99% of the ICERs were less than $50,000 per life-year saved and per QALY. Conclusions: Our updated cost-effectiveness estimates are supportive of the economic value of the 21-gene RS assay in the setting of node-negative, estrogen receptor–positive breast cancer.
Outcomes from an electronic medical record (EMR)-based standardized tobacco assessment and cessation program in a NCI-designated comprehensive cancer center.
Authors: Warren Graham Walter , Zevon Michael , Hyland Andrew , Hysert Pat , Reed Robert , Long Mary Ann , Houston Teresa , Mahoney Martin , Demmy Todd L. , Cummings K. Michael 
Published: March 2020

1529 Background: Tobacco assessment and cessation is advocated by ASCO and national clinical oncology guidelines, but there is little information on large scale clinically efficient models to assess tobacco use and provide cessation in a structured evidence based manner. Automation through the electronic medical record (EMR) could reduce subjective interpretation by clinicians and assist in increasing data tracking accuracy to enhance meaningful use initiatives. Methods: A standard set of evidence based tobacco assessment questions were incorporated into an annotated fixed-variable response system in the EMR delivered by nursing at initial consult and at follow-up. A logic based EMR referral system was developed to determine patient eligibility for mandatory automated referral to a dedicated tobacco cessation service. An evidence based institutional clinical cessation program was developed to provide cessation support to referred patients. The evidence based screening and referral algorithms will be presented. Results: Over 13 months, 677 patients were referred and 529 patients were successfully contacted to date for cessation support. In the 529 patients, 21 (3.9%) were inappropriate referrals (never smokers or long term former smokers), 48 patients (9.1%) did not want to enroll, but wanted to discuss cessation at a later date. Notably, only 18 patients (3.4%) refused any intervention. In a total of 415 patients enrolled in the cessation program, 104 patients (25.1%) were thinking about quitting (contemplation), 134 patients (32.3%) were preparing to quit, 169 patients (40.7%) were quitting (action phase), and 8 patients (1.9%) have relapsed. Tobacco assessments and automated referrals through the EMR took a median of 4 minutes to complete. Conclusions: A large volume of patients were screened and referred to a dedicated cessation program with low patient refusal for intervention without impeding physician workflow. These data suggest that this nursing driven EMR based assessment is a highly efficient clinical model for tobacco assessment and cessation.