bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urgent cancer genetic counseling and testing for young, premenopausal women with breast cancer (BC): Impact on surgical decision-making for contralateral risk-reducing mastectomy.
Authors: Mai Phuong L. , Dettwyler Shenin , Johnson Ronald , McAuliffe Priscilla F. , Steiman Jennifer G. , Thull Darcy , Diego Emilia 
Published: May 2020

1533 Background: In women newly diagnosed with unilateral breast cancer (BC), contralateral risk-reducing mastectomy (CRRM) to decrease risk for additional primary BC is an appropriate option for some individuals, such as those with significantly increased risk due to a pathogenic variant (PV) in a breast cancer predisposition gene. Genetic testing at the time of BC diagnosis for young women has become more available and could aid in the decision-making process. We evaluated the trends for CRRM in a cohort of women diagnosed with BC at age ≤45 years who were seen in a multidisciplinary clinic where genetic counseling and testing is offered to each patient. Methods: A single institution, prospectively maintained database of patients seen in a BC multidisciplinary clinic between November 2014 and June 2019 was reviewed. Patients were included if they had non-metastatic, unilateral BC diagnosed ≤45 years of age, and underwent genetic testing at the time of BC diagnosis. Associations between surgical treatment (lumpectomy, mastectomy, or mastectomy with CRRM) and age at diagnosis, BC stage, family history, and genetic testing results were evaluated. Results: 184 patients were included in the analysis. The prevalence of a PV in a breast cancer predisposition gene was 15.8% (29/184; 1 in ATM, 12 in BRCA1, 8 in BRCA2, 5 in CH EK2, 2 in NBN, and 1 in NF1). 69% of the PV were in BRCA1 and BRCA2. 126 (68.4%) tested negative, and 29 (15.8%) had a variant of uncertain significance (VUS) in various genes. Overall, 63 patients (34.2%) elected to have CRRM. Of the 29 patients with a PV, 24 (82.8%) had CRRM. Women who chose CRRM were younger, more likely to test positive for a PV in a breast cancer predisposition gene, and more likely to have a significant family history of breast and/or ovarian cancer. Among the 155 patients who tested negative or had a VUS, there was no statistically significant association between CRRM and age (p = 0.58), test result (negative vs. VUS. p = 0.12), or family history (p = 0.32). Conclusions: For young women with BC seen in a multidisciplinary clinic, a younger age, significant family history, and positive genetic testing result were found to be associated with the decision to undergo CRRM. Among those without a genetic predisposition, having a VUS result was not associated with choosing CRRM. Incorporation of genetic services in the initial evaluation of young patients newly diagnosed with BC could add relevant information in surgical decision making and promote risk-appropriate management.
Heterozygous germline ATM mutations in breast cancer: A single academic center experience.
Authors: Konde Anish S , Ivan Kristina , Klavanian Jeannie , Rangarajan Tara , Jaiyesimi Ishmael A. , Zakalik Dana 
Published: May 2020

1537 Background: Heterozygous germline ATM mutation carriers have an increased risk of developing breast, pancreas, and other cancers. The clinical and pathologic characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing (MGPT) between 2013-2019 and identified to harbor ATM mutations were included in the study. We evaluated demographics, pathology, and surgical management of our ATM mutation carriers with breast cancer. Results: At total of 319 individuals were identified to have variants in ATM, of which 114 were pathogenic/likely pathogenic. The majority of patients were female (82%) and Caucasian (88%). A total of 56 patients (49%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 39). Nine individuals had more than one primary malignancy. The mean age at breast cancer diagnosis was 52, with a range of 25-82. The majority of patients had invasive ductal carcinoma (74%), grade 2 or 3 (90%), and ER and /or PR positive (87%). Of those with known HER2 status, 24% were positive. Thirty-nine percent of patients were lymph node positive, and 42% had lymphovascular invasion. The most common stage at diagnosis was 2 (53%). Of the 39 mutation carriers with breast cancer, 16 (42%) received radiation therapy, and 16 underwent bilateral mastectomy. Of 114 ATM positive patients, there were 55 distinct variants. Sixteen (14%) individuals had a mutation in additional cancer predisposition genes. One variant, c.5015delG, was identified in ten patients in a large, consanguineous Iraqi family with an extensive history of pancreatic and other cancers. Eight individuals were identified to have the known high-penetrance variant, c.7271T > G. Conclusions: Our study describes the clinical and pathological characteristics of ATM mutations carriers with breast cancer. The majority of patients had intermediate to high grade disease, hormone receptor positive, with a suggestion of a higher rate of HER2 positivity and lymph node involvement. Additional studies are needed to elucidate the unique characteristics of ATM-associated breast cancer, which may have implications for personalized management.
First year outcomes of an initiative to increase BRCA testing among NCCN guideline-eligible breast cancer patients within a large community OCM practice.
Authors: Waterhouse David Michael , Guinigundo Andrew , Brown Aimee , Davies Dan , Jones Lauren , Mendenhall Molly 
Published: May 2020

1540 Background: Pathogenic variants in BRCA1/BRCA2 can affect a breast CA pts care: preventative interventions, surgical decisions, medical treatments, screening, and family counseling. National data suggests significant non-adherence to NCCN testing guidelines, with only 1/3 of eligible pts referred for genetic services. In 2018, OHC (Cincinnati) launched an APP-centric genetics program. Specially trained APPs carry out genetic counseling and order NCCN-compliant testing. Early data suggested a significant deficit in physician-driven referrals. From 1/01/18 - 07/31/18, 138 new breast pts were estimated to be NCCN guideline-eligible. Only 28 (20%) pts received genetic services. Methods: In 2019, the OHC genetics team implemented a standardized screening process for every new breast CA pt. An EMR template (iKnowMed G2) that included NCCN guidelines was created for initial breast CA consultation and Oncology Care Model (OCM) treatment planning. All pts, not just OCM pts, are subject to OCM treatment planning. This automated screening method ensured all breast CA pts were screened, drastically increasing compliance. Through integration of genetics screening into the templates, pts meeting NCCN criteria for testing are reflexively referred for genetic counseling. With USON/McKesson, integrated data fields were developed in the EMR to automate data collection. Results: From 01/01/19 – 12/31/19, 717 new breast CA pts were seen at OHC. 676/717 (94%) were screened. Of those screened, 279 new breast CA pts met NCCN criteria for BRCA testing. 140 (50%) eligible new pts had appts with the genetics team. Another 50 (18%) had confirmed testing outside of OHC. 57 (20%) refused appts and/or testing. 32 (11%) did not have appts, representing screen fails. Referrals in non-breast CA pts also increased by 127%; 604 (2019) vs 264 (2018) suggesting a halo effect. Analyses suggest the program to be economically viable, with a financial growth rate of 127%. Conclusions: EMR templates embedded with the NCCN guidelines for reflex genetics referral can appropriately increase the utilization of genetic services. Breast genetics screening and resultant appt/testing rates increased significantly 2019 vs 2018. Success in BRCA testing in breast CA will lead to expansion to other cancers and genes. Implementation of structured EMR genetics data fields can automate data collection and measure compliance. Integration of genetics screening into universal OCM treatment planning is feasible, economically viable and scalable.
Relationship between CYP2D6 genotype, tamoxifen metabolites, and adverse events, tumor biomarkers and breast cancer recurrence in a low-dose phase III trial in noninvasive disease.
Authors: De Censi Andrea , Johansson Harriet Ann , Helland Thomas , Puntoni Matteo , Buttiron Webber Tania , Macis Debora , Aristarco Valentina , Briata Irene Maria , Serrano Davide , D'Amico Mauro , Bifulco Ersilia , Hustad Steinar , Søiland Håvard , Bonanni Bernardo , Mellgren Gunnar 
Published: May 2020

1553 Background: Low dose tamoxifen (T, 5 mg/d) given for 3 years halved recurrence in 500 women with non-invasive disease (DeCensi et al. JCO 2019). Retrospective studies with 20 mg/d have shown an association between low levels of endoxifen (9-16 nM) or Z-4OHtam (3.26 nM) and recurrence, but recent prospective studies have not confirmed these findings. We measured CYP2D6 genotype and 8 metabolite levels to determine their associations with adverse events, tumor biomarkers (IGF-I, SHBG, C-reactive protein, CRP) and breast cancer recurrence. Methods: CYP2D6 genotyping was performed in the T arm (n = 183) as previously described (Johansson H et al. BCRT 2016). T and metabolites were measured at 1 (n = 169) and 3 y (n = 152) as previously described (Helland T et al. BCR 2017). We tested linear relationships between metabolite levels and biomarkers, adjusting for age, BMI, treatment compliance and baseline biomarker levels. Cumulative incidence of recurrence according to endoxifen levels was calculated by the Cox model. Results: Endoxifen concentrations were associated to CYP2D6 metabolizer status (p < 0.001). Median (IQR) endoxifen levels were 8.4 (5.2-11.3) and 8.8 (5.8-11.5) at 1 and 3 y, with only 42% and 47% of subjects reaching 9 nM. Median endoxifen levels were related to pill count (5.5, 7.1 and 9.0 nM/L for medication possession rate < 83.3%, 83.4-99.9%, 100%, respectively). There was no difference in metabolite levels and menopausal symptoms. There was an inverse relationship between endoxifen and endometrial thickness at 3 y (p = 0.04), and between endoxifen or tamoxifen levels and IGF-I levels at 3 y (p = 0.001). T levels were positively associated with SHBG levels in postmenopausal women (p-interaction = 0.04). Endoxifen, T and 4OHtam decreased CRP, with a greater effect in premenopausal women (p-interaction = 0.02). An increase in CRP after 3 years was associated with a HR of 4.37 (95% CI, 1.14-16.73, P = 0.03) of recurrence compared to women with no increase of CRP. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3-11.4) in patients who recurred vs 7.5 (5.1-10.2) in those who did not recur (p = 0.6), although this comparison was underpowered. Conclusions: T levels themselves may contribute to clinical activity by decreasing IGF-I and increasing SHBG. Elevated CRP is a predictive factor for recurrence which is down-regulated by T and metabolites. Endoxifen is below 9 nM in the majority of subjects treated with 5 mg/day, although this threshold was obtained in studies up to 20 years. Clinical trial information: NCT01357772.
Adoption of opportunistic salpingectomy for ovarian cancer prevention: Results from a nationwide sample of privately insured women.
Authors: Karia Pritesh S , Joshu Corinne E , Rosenshein Neil B. , Visvanathan Kala 
Published: May 2020

1561 Background: Recent evidence indicates that the Fallopian tube is the site of origin for many high-grade serous ovarian cancers, particularly in BRCA carriers. This has led to the emergence of opportunistic salpingectomy (OS) as a novel ovarian cancer prevention strategy. Despite limited data, some national societies now recommend OS for ovarian cancer prevention during benign hysterectomy or in place of tubal ligation for sterilization in average-risk women. We assessed patient characteristics associated with increased likelihood of OS and national trends in OS adoption before and after release of recommendations. Methods: Data from MarketScan were used to identify women who underwent hysterectomy, tubal ligation, and OS from 2010-2017. Rates of OS were compared and interrupted time series analysis with segmented Poisson regression was used to examine immediate and persistent changes in OS rates before and after recommendations. Rates were calculated quarterly and models were adjusted for age and seasonality. Results: A total of 309,574 tubal ligations, 13,574 OS for sterilization, 293,000 hysterectomies, 22,798 hysterectomies with OS were included. Quarterly rates of OS for sterilization and hysterectomy with OS were 3.13 and 4.82 per 100,000 women, respectively. About 92% of OS for sterilization and 56% of hysterectomy with OS were performed in women < 45 years. The most common indication for hysterectomy with OS was uterine fibroids (46%). About 8% of OS for sterilization and 10% of hysterectomy with OS were performed in women with a family history of breast or ovarian cancer. After adjusting for age and seasonality, there was a 250% immediate increase (RR: 3.50; 95% CI: 2.59-4.72) followed by a 14% (RR: 1.14; 95% CI: 1.10-1.18) persistent increase in the quarterly rate of OS for sterilization after versus before recommendation release. There was a 109% immediate increase (RR: 2.09; 95% CI: 1.15-3.81) in the quarterly rate of hysterectomy with OS after versus before recommendation release. No persistent change in the rate of hysterectomy with OS was observed. Significant declines in hysterectomy and tubal ligation rates were observed and these declines were temporally associated with the release of recommendations. Conclusions: OS for ovarian cancer prevention has rapidly diffused into clinical practice with the speed of adoption bolstered by recommendations from national societies. Future studies evaluating the overall efficacy and long-term complications of OS are needed to support its continued widespread use.
Dietary advanced glycation end products (AGEs) and breast cancer mortality in the women’s health initiative (WHI).
Authors: Peterson Lindsay Leuthen , Omofuma Omonefe , Turner David P , Merchant Anwar , Zhang Jiajia , Neuhouser Marian L. , Snetselaar Linda , Caan Bette Jane , Shadyab Aladdin H. , Saquib Nazmus , Thomson Cynthia A. , Uribarri Jaime , Steck Susan 
Published: May 2020

1570 Background: Breast cancer (BrCa) is the second leading cause of cancer death and constitutes about 14% of total cancer deaths among US women. Advanced glycation end-products (AGEs) are implicated in chronic diseases including cancer and cardiovascular diseases (CVD). AGEs are naturally found in animal products and processed foods, and preparing food at high temperatures increases AGE formation. Our goal was to assess the association between post-diagnosis dietary NƐ-carboxymethyl-lysine (CML)-AGE intake, a common measure of AGE, and mortality from all-causes, BrCa and CVD among participants with invasive BrCa in the Women’s Health Initiative (WHI). Methods: The WHI enrolled postmenopausal women aged 50 to 79 years from 1993-1998 into randomized controlled trials and a prospective observational study to examine causes of morbidity and mortality. In this analysis, we included 2,073 women diagnosed with invasive BrCa during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis, had energy intakes between ≥600 kcal/day and ≤5000 kcal/day, and had CML-AGE intake data available. Women were followed from BrCa diagnosis until death or censoring through March 2018. Cox proportional hazards regression models estimated the hazard ratios (HR) and 95% CIs of mortality risk from all-causes, BrCa and CVD by tertiles of dietary CML-AGE intake with adjustment for age, income, race/ethnicity, study arm, time from diagnosis to FFQ completion, education, physical activity, smoking, BMI, ER/PR status, diagnosis stage, postmenopausal hormone use, intake of energy, alcohol, fat, red and processed meats. Results: After a median 15.1 years of follow-up, 642 deaths were reported including 198 BrCa-specific and 129 CVD-specific deaths. The average time from BrCa diagnosis to FFQ completion was 1.5 years. Compared to the lowest tertile of CML-AGE intake, there was an increased risk in the highest tertile for all-cause mortality (HR: 1.51, 95% CI: 1.17-1.94), BrCa (HR: 1.86, 95% CI: 1.19-2.91) and CVD (HR: 2.14, 95% CI: 1.19-3.84) mortality. Conclusions: Higher dietary AGE intake after BrCa diagnosis in postmenopausal women was associated with increased risk of mortality from all-causes, BrCa and CVD. Exposure to AGEs could be modified through dietary counseling and evaluated in relation to reduced mortality risk after BrCa diagnosis.
Burden of genetic testing in an academic biobank by pathological and family history-based criteria in prostate cancer (PCa).
Authors: Ding James , Feld Emily , Le Anh , Sanchez Pauleen , Powers Jacquelyn , Doucette Abigail , Gabriel Peter Edward , McLaughlin Michael , Kember Rachel , Weaver Joellen , Judy Renae , Rader Daniel , Damrauer Scott , Lee Daniel , Narayan Vivek , Domchek Susan M. , Schwartz Lauren , Maxwell Kara Noelle 
Published: May 2020

1576 Background: Approximately 5% of localized PCa and 12% of metastatic PCa are associated with germline mutations in DNA repair genes. The National Comprehensive Cancer Network (NCCN) issued genetic testing guidelines to identify PCa patients (pts) likely to harbor a germline DNA repair mutation. The overall burden of this guideline-based, resource-intensive genetic testing is unknown. Using supervised phenotype-genotype information extraction algorithms, we determined the projected genetic testing burden at a single institution adhering to NCCN PCa genetic testing guidelines. Methods: A PCa cohort of 2127 pts was identified from the Penn Medicine BioBank via ICD 9/10 codes. Phenotypic data were extracted from the Penn Medicine Cancer Registry and electronic health record systems via natural language processing and manual chart review. Pts were classified based on 9 germline genetic testing criteria outlined in the NCCN PCa guidelines (Version 4.2019). Results: 895/2127 pts met at least 1 of the 9 NCCN genetic testing criteria, corresponding to a 42.1% overall genetic testing burden. 35.2% qualified for testing via high-risk localized PCa and 6.4% qualified via metastatic disease. Of the pts with localized PCa (n=2014), 15.1% qualified for genetic testing via high Gleason score, 5.1% via high-risk family history, 3.7% via PSA>20ng/mL, 8.7% via Ashkenazi Jewish descent, and 0.8% via intraductal/ductal histology. Conclusions: In this single-center PCa cohort, germline genetic testing was NCCN-guideline recommended for a larger proportion of pts than would otherwise be expected based on previously published reports. Future studies are needed to validate the sensitivity and specificity of these criteria for identifying germline mutations. Our study also highlights a need for novel methods to improve the efficiency of genetic testing for a large cohort. [Table: see text]
Diagnostic yield of germline genetic testing following tumor testing in prostate cancer patients.
Authors: Das Kingshuk , Lincoln Stephen E , Ngo Nhu , Pineda Alvarez Daniel Esteban , Yang Shan , Michalski Scott T. , Nielsen Sarah M. , Esplin Edward D. , Nussbaum Robert Luke 
Published: May 2020

1591 Background: NCCN guidelines recommend germline testing for patients with localized or advanced prostate cancer meeting family history or clinical/pathologic criteria. However, the guidelines for somatic molecular analysis generally consider advanced disease only, primarily to inform therapy. As the analytical and clinical specifications of both testing modalities differ accordingly, we examined the results of germline testing following prior somatic testing. Methods: We reviewed somatic and germline variants in an otherwise unselected consecutive series of patients who: (a) had a current or previous diagnosis of prostate cancer; (b) had undergone tumor sequencing; and (c) were referred for germline testing. Indications for germline testing included: potential germline origin of somatic test result, treatment or surgical planning, personal or family history, and patient concern. Results: 208 patients met study criteria of whom 81 (39%) harbored a pathogenic germline variant (PGV) in a cancer predisposition gene. Certain genes were more likely to harbor germline variants, and 98% (81) of PGVs were potentially actionable (Table). 9.6% of PGVs were not reported by somatic testing, reflecting analytical limitations of the somatic testing. Of note, 11 patients (14%) had PGVs identified after diagnosis of a subsequent primary malignancy. Conclusions: The high PGV rate of 39% was unexpected, given reported rates of 11.8% in patients with metastatic prostate cancer and 6% in high-risk localized disease (NCCN)--even considering potential clinician ascertainment bias. This finding, the potential clinical utility of 98% of PGVs identified, the significant proportion unreported by somatic testing, and the fraction of patients diagnosed with a PGV after a subsequent malignancy all suggest that germline testing is an underutilized tool in the care of prostate cancer patients and their families. [Table: see text]
Outcomes of lung cancer screening among cancer survivors: An NCCN institution experience.
Authors: Maller Bradley , Simmons Vani Nath , Byrne Margaret M , Tanvetyanon Tawee 
Published: May 2020

1595 Background: In 2013, the USPTF recommended low-dose CT (LDCT) screening for individuals at high risk of lung cancer based on data from the National Lung Screening Trial. However, the trial excluded participants with cancer diagnosis < 5 years except for non-melanoma skin cancer, making it unclear whether the data will be generalizable to cancer survivors. This population, while at increased risk of secondary lung cancer, may be prone to false positive results due to anatomic defects or recurrent cancers. Our NCCN institution serves a large number of cancer survivors. We evaluated the outcomes of LDCT screening and the adherence to annual screening among cancer survivors, compared with individuals without cancer history (IWC). Methods: Prospectively maintained database of LDCT screening participants was analyzed. Eligibility was per NCCN criteria and cancer survivors needing regular chest CT were not offered LDCT. Participants were asked to complete a self-administered questionnaire on risk factors. Positive result was defined as Lung-RADS ≥3, corresponding to nodule ≥6 mm. Adherence to LDCT screening was defined as having T1 screening, excluding those < 18 months from T0 at time of analysis. Predicted risk of lung cancer was calculated per PLCOm2012 model. Results: To date, 454 subjects have undergone LDCT screening. Positive results occurred in 60 subjects (13.2%) at T0; lung cancer was diagnosed in 10 subjects (2.2%); and other cancers were diagnosed in 5 subjects (1.1%). There were 152 cancer survivors, including survivors of breast (52), prostate (26), bladder or kidney (19), lung (14), and head and neck cancer (13). The median time from cancer treatment to LDCT screening was 6 years (range 0-55). Cancer survivors were older than IWC: median age 67.4 vs. 63.5 years ( p< 0.001) and more likely to be active smokers: 37.5% vs. 29.5%, ( p= 0.09). The median predicted risk of lung cancer at 6 year was 5.5% vs. 3.2%, ( p= 0.15). No significant difference in the screening outcomes was found between groups. Among cancer survivors (N = 152), positive screening occurred in 15 (9.9%); lung cancer was diagnosed in 1 (0.7%); and other cancers were diagnosed in 3 subjects (1.9%). Non-adherence to LDCT screening occurred in 31 out of 152 cancer survivors (20.4%), compared with 81 out of 262 (30.9%) IWC, ( p= 0.02). Conclusions: About one-third of LDCT screenings at this NCCN institution occurred among cancer survivors. We found no evidence of increased false positive results. However, a higher rate of adherence to annual screening was observed among cancer survivors than IWC.