bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-06-06: Frequency of mutations in multi-gene panel testing of 3,011 breast cancer patients
Authors: Zhou AY , van den Akker J , Zimmer A , McFadden W 
Published: February 2018

Abstract
Objectives:
Here, we describe the characteristics of 3,011 individuals with a self-reported diagnosis of breast cancer who received a multi-gene panel genetic test for hereditary cancer risk.
Methods:
These 3,011 patients were referred physician order for a multi-gene, next generation sequencing panel for hereditary cancer risk. Analysis was limited to 19 genes associated with hereditary breast and ovarian cancer (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, TP53). All patient demographic information was collected via a self-reported online health history questionnaire.
Results: In this cohort, the median reported age at breast cancer diagnosis was 49.3. Overall, 360 pathogenic or likely pathogenic variants were identified and reported. A total of 344 individuals were found to carry a single pathogenic mutation in one of the 19 genes analyzed, and 8 individuals were found to carry two concurrent pathogenic mutations in different genes. Notably, 173 of the 360 mutations identified were reported in the BRCA1 and BRCA2 genes (48.1%), yielding an overall BRCA1 and BRCA2 mutation carrier rate of 5.7%. Additionally, 12.2% of the cohort reported having bilateral breast cancer. The mutation carrier rate amongst these individuals was 15.0% (50/334), 60.8% of the mutations found in these individuals were in BRCA1 or BRCA2, and the average age at breast cancer diagnosis was 49.4 (43.3 amongst mutation carriers). In the entire cohort, a pathogenic mutation was identified in 15 of the 19 genes analyzed.
Conclusion:
In summary, the overall mutation carrier rate in this cohort for breast and ovarian cancer risk genes was 11.7% (352/3,011). Taken together, these data support the recommendation that all patients with breast cancer should undergo germline testing for hereditary cancer risk.
Citation Format: Zhou AY, van den Akker J, Zimmer A, McFadden W. Frequency of mutations in multi-gene panel testing of 3,011 breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-06.
Abstract P4-06-09: Addition of a remote genetic counselor to the breast specialist's team improves clinical decision-making
Authors: Rosen B , O'Leary E , Shan Y , Pat W , Peter B 
Published: February 2018

Abstract
Background: There is a shortage of trained genetic counselors (GC) and often long wait times for appointments, resulting in other specialists frequently ordering genetic testing. However, non-genetic specialists, including breast surgeons, find it difficult to stay current in genetics due to rapid advances in gene discovery, expanded panel offerings, and frequent changes to professional guidelines. We tested a novel model for hereditary cancer risk assessment where breast surgeons had “on demand” access to a remote laboratory-based genetic counselor for peer to peer consultation. In this study we sought to determine the impact this model has on breast surgeons' routinely ordering genetic testing including test identification, ordering patterns, and medical management.
Methods: An IRB approved multi-center prospective study involved 14 community-based breast cancer surgeons experienced with hereditary cancer risk assessment without a genetic counselor as part of their practice. Cases were all discussed with a remote Invitae GC to determine testing eligibility and selection. Physicians had the option to utilize remote GCs to discuss results or to refer to traditional genetic counseling services. Pre and post-test surveys were completed for each patient by the testing physician. To protect patient privacy, a unique case ID was used to link patient test data with identifying data.
Results: A total of 192 patients were evaluated with median age of 52. Risk assessment via BRCAPRO and the Hughes Risk model were performed on 98% of patients by the physicians. 65% of patients met NCCN guidelines for testing. Pathogenic mutations were found in 14% of patients. Breast surgeons changed their test selection 21% of the time after discussion with a GC. They called to discuss results in 47% of cases and medical management changes were incorporated in 15% of these cases based on discussion with a remote GC.
Conclusions: Remote GC provider support assisted physicians in facilitating customized test selection, aided in navigating challenging counseling cases, and impacted clinical management. This service may serve as a viable, effective model for 'on demand' genetic counseling support and may be a novel opportunity to expand genetic testing in a breast surgery setting.
Citation Format: Rosen B, O'Leary E, Shan Y, Pat W, Peter B. Addition of a remote genetic counselor to the breast specialist's team improves clinical decision-making [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-09.
Abstract P4-06-12: Different patterns of risk reducing decisions in affected or unaffected BRCA mutation carriers
Authors: Lee EG , Kang H , Park SJ , Han JH , Jung S-Y , Lee S , Kang H-S , Park B , Kong S-Y , Lim MC , Park S-Y , Lee ES 
Published: February 2018

Abstract
BACKGROUND
Risk-reducing (RR) management decreases the risk of breast cancer and BRCA related gynecologic cancer. However, there are fewer reports on the RR management in Asia compared to Western countries.The aim of this study is to identify risk reducing management patterns with BRCA1 or BRCA2 mutation carriers.
METHODS
The study group consisted of all consecutive 1104 breast cancer, ovarian patients and their families of high-risk patients who underwent BRCA gene testing in National Cancer Center, Korea from 2008 to 2016. A total 220 BRCA mutations (19.9%) were detected with 125(11.3%) of BRCA1 gene and 95 (8.6%) of BRCA2 gene.
RESULTS
Out of 220 BRCA mutations carriers, they were consisted of 83 breast cancers, 10 ovarian cancers, 7 both cancers, and 120 unaffected carriers. Among them, 42 were men and 178 were women. About 90 % (198/ 220) had the familial history of breast, ovarian or both malignancies (113 in BRCA1 and 85 in BRCA2 mutation (p=0.821)).
All 42 men chose surveillance. Among 178 female BRCA mutation carriers, 98(55.1%) underwent risk reducing management including 18(10.1%) of chemoprevention, and 80(49.9%) had risk-reducing surgeries (RRSs) (1 case of risk-reducing mastectomy, 76 of risk reducing bilateral salphingo-oophorectomy (RRSO), and 3 of both) and 80 (54.9%) chose only intensive surveillance for both of breast and ovary cancer.
In affected carriers with breast cancer, 59 (71.1%) underwent RR management (1 case of risk reducing mastectomy, 53 of RRSO, 3 of both surgery, and 2 of chemoprevention). There was no risk reducing management in affected carrier with ovarian cancer patients. In 78 unaffected women carriers, 39(50.0%) women received RR management (23(29.5%) cases of RRSO and 16(20.5%) cases of chemoprevention). The rates of RRSs have increased annually since the 2013 year, (prior to 2013 vs. since 2013, RRSs 28.6% (6 cases/21 carriers) vs. 37.2% (74/199), p&lt;0.01).
CONCLUSION
This study was conducted on the largest numbers of BRCA mutation carriers in Asian countries. RRSO is the more preferred management for affected carriers with breast cancer or unaffected carriers. The results might be explained by the severity of the illness and that RRSO was only reimbursed RR strategy from the Korean Government Insurance. Tailored genetic counseling and insurance policy may enhance overall levels of RR management.
Citation Format: Lee EG, Kang H, Park SJ, Han JH, Jung S-Y, Lee S, Kang H-S, Park B, Kong S-Y, Lim MC, Park S-Y, Lee ES. Different patterns of risk reducing decisions in affected or unaffected BRCA mutation carriers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-12.
Abstract P4-06-16: Frequency of pathogenic mutation in patients at high risk for hereditary breast cancer
Authors: Shin H-C , Yoo T-K , Lee H-B , Moon H-G , Noh D-Y , Han W 
Published: February 2018

Abstract
Background: Next-generation sequencing technology allows the simultaneous sequencing of multiple target genes. We developed a gene panel containing 64 genes which were associated with various hereditary cancers. This study was performed to evaluate the frequency of pathogenic mutations associated with hereditary cancer among Korean patients at high risk hereditary breast cancer using multi-gene sequencing panel.
Methods: A total of 252 breast cancer patients with high-risk hereditary cancer were included. Among them, 179 patients (71.0%) had multiple primary cancers including breast cancer, 27 patients (10.7%) were diagnosed with bilateral breast cancer at age 40 or younger. Thirty-five patients (13.9%) had breast cancer family history of more than 2 relatives. With the 64-gene panel, sequence variants were detected by next-generation sequencing technology.
Results: Sixty seven patients (26.8%) were found to have 77 germline pathogenic mutations, 12 in BRCA1, 13 in BRCA2, 9 in CDH1, 3 in FH, 5 in MSH2, 2 in MSH6, 4 in NAT1, 6 in PTCH1, 3 in RAD51, 7 in RET, 4 in SPINK1, 3 in TP53 and one each in ALK, BRIP1, CHEK2, MLH2, MUTYH, and PTEN. In 20 patients (4.0%), 2 (n=9) or 3 (n=1) pathogenic mutations were detected. In 227 patients with BRCA1/2 negative, CDH1 (n=7), RET (n=7), PTCH1 (n=5), and MSH2 (n=5) were the most prevalent pathogenic mutations.
Conclusions: The 64 gene panel detected germline pathogenic mutations in 26.8% of Korean breast cancer patients with feature of hereditary cancer. Mutations of BRCA1, BRCA2, CDH1, RET, and PTCH1 were the most prevalent variants.Mutation carriers were considered as high risk to develop malignancy and recommended to receive genetic counseling and intensive cancer screening.
Citation Format: Shin H-C, Yoo T-K, Lee H-B, Moon H-G, Noh D-Y, Han W. Frequency of pathogenic mutation in patients at high risk for hereditary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-16.
Abstract P4-07-01: Assessment of the hereditary component in 94 cancer predisposition genes to triple negative breast cancer
Authors: Ellsworth RE , Lovejoy LA , Shriver CD 
Published: February 2018

Abstract
Background: In women with triple negative breast cancer (TNBC) unselected for age or family history, 8-14% and 5% of patients harbor germline mutations in BRCA1 and BRCA2, respectively. Diagnosis of TNBC &lt;60 years of age is one of the NCCN criterion for genetic testing of BRCA1 and BRCA2. The contribution of germline mutations in other cancer predisposition genes to TNBC, is, however, not well-studied.
Methods: TNBC was classified as tumors with &lt;1% positively staining cells for ER and PR and HER2 = 0+, 1+ or 2+/not amplified. Genomic DNA was isolated from blood samples and targeted sequencing was performed using the TruSight Cancer panel (Illumina). Pathogenic mutations were identified using VariantStudio and classified as pathogenic, uncertain significance (VUS) or benign using ClinVar.
Results: 196 female patients diagnosed with TNBC 2001-2014 had genomic DNA available. Average age at diagnosis was 52.8 years (range 34.1-83.4 years). The majority of patients were of European (66%) or African (31%) American ancestry; 26% had a family history and 13% had died of disease with an average time to death of 2.81 years. Twenty-three (12%) of women with TNBC had pathogenic mutations in breast cancer genes BRCA1 (n=14), BRCA2 (n=5), PALB2 (n=1) and CHEK2 (n=3), two women had mutations in the colon cancer genes MUTYH, one had a mutation in the ovarian cancer gene BRIP1, and an additional three women had pathogenic mutations in cancer predisposition genes FANCD2, SDHB and XPC. An additional 42 women had VUS in 20 genes, including one in BRCA1 and 5 in BRCA2.
Discussion: Although the majority of pathogenic mutations in this cohort of women with TNBC were in the BRCA1 and BRCA2 genes (10%), panel testing allowed for the detection of mutations in other breast (2%), colon (1%), ovarian (1%) and other cancer (2%) predisposition genes. Panel testing thus identifies genes other than BRCA1/2 associated with increased risk of TNBC and may incidentally identify women who would benefit from enhanced surveillance for other cancers.
The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences or any other agency of the U.S. Government.
Citation Format: Ellsworth RE, Lovejoy LA, Shriver CD. Assessment of the hereditary component in 94 cancer predisposition genes to triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-07-01.
Abstract P4-10-18: Medismart-Oncosmart: A low-cost private initiative to improve health care access in the middle-income country of Costa Rica. Overview of the breast cancer screening program
Authors: Wiernik A , Lami Casaus L , Durman M , Herrera Guido R 
Published: February 2018

Abstract
Background: Costa Rica is a middle-income country in Central America with a public, government run, universal health care system which provides coverage to over 95% of the population. Despite being recognized as one of the best health care systems in Latin America, recent national reports suggest that up to 15% of the population is currently on a waiting list for a medical visit or procedure. The impact of the national breast cancer screening program is unknown as the country's health care system and the national cancer registry fail to report statistical variables like screening waiting lists, breast screening coverage, stage at diagnosis, time from screening to biopsy, breast cancer subtypes, breast cancer mortality by stage, among others.
Methods: In 2014, the private health plan Medismart partnered with the private Hospital Metropolitano network with the mission of developing a low-cost health care system that provides efficient access and affordable health care services to its affiliates. Medismart's health care plan costs $12 a month per member ($6 per additional affiliated family member) and uses a copay model for health care services utilized by its beneficiaries. In 2016, Oncosmart, a program of Medismart, was developed with the goal of implementing population based screening, diagnostic procedures, cancer treatment, and survivorship care to its members. The program has no restrictions on pre-existing conditions.
Results: From January 2015 to April 2017, Medismart subscribed 50,122 members. During the first 12 months of launching the breast screening program, 3634 women (32% of target population of 11058 women over 40 years old) underwent breast cancer screening mammography, breast ultrasound or both at the Hospital Metropolitano network. The copayment price of mammography screening for Medismart members is $26 and the copayment price for breast ultrasound screening is $38. Of the women who underwent screening in this period, 153 required a breast biopsy and all biopsies performed at the Metropolitano hospital were completed within 30 days from the abnormal imaging study.
Conclusion: Medismart-Oncosmart is a low cost and efficient private initiative that improves access to breast cancer screening in Costa Rica.
Citation Format: Wiernik A, Lami Casaus L, Durman M, Herrera Guido R. Medismart-Oncosmart: A low-cost private initiative to improve health care access in the middle-income country of Costa Rica. Overview of the breast cancer screening program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-18.
Abstract P4-11-04: Talking about risk in the context of GEomic profiling tests (TARGET)
Authors: Fallowfield LJ , Jenkins VA 
Published: February 2018

Abstract
Background: Risk of recurrence scores from genomic profiling tests such as OncotypeDX® and EndoPredict® are being used increasingly with other clinico-pathologic features to help determine the likely benefit of adjuvant chemotherapy in early stage breast cancer. Decision-making requires the balancing of likely absolute benefits in terms of preventing recurrence versus the treatment related side effects. Health literacy and numeracy skills in the general population are often poor thus explaining risk and uncertainty can be confusing especially when set against a backdrop of fear and anxiety. As clinicians are facing more of these types of conversations with their patients we developed an educational program to help when discussing genomic test results.
Methods: The development of the educational package followed discussions with key clinicians who routinely used genomic profiling tests, clinician-scientists and a review of the risk literature. We mapped out the difficulties they encountered when explaining high, intermediate and low risk test results together with the added challenges faced when communicating with patients with different personality and socio-educational characteristics. As clinicians and their patients may both have a measurable intolerance to uncertainty this may contribute irrespective of the recurrence score (RS) to seemingly irrational decisions about treatment. We rehearsed simulated patients (actors) experienced in improvisation to create different characters and filmed unscripted genomic test result consultations with cancer clinicians. This process proved successful in previous educational initiatives aimed at improving communication about clinical trials. (Jenkins et al 2006; Fallowfield et al 2012).
Results: The educational package comprises an interview with Professor Mitch Dowsett explaining the science behind gene expression profiling tests, a lecture on the psychology of risk with group exercises and strategies on how to communicate together with 5 filmed scenarios with a timecoded facilitator handbook. The scenarios depicted are based on real clinical situations and demonstrate some of the issues discussing RS with low risk patients who nevertheless wish to have chemotherapy as well as high risk patients who are averse to chemotherapy.
Conclusion: Discussions about the logic and rationale behind different treatment recommendations for breast cancer have become increasingly complex. Clinicians need an increased repertoire of communication skills to explain risks and benefits. We are now evaluating the efficacy of TARGET prior to training facilitators to roll the program out.
Citation Format: Fallowfield LJ, Jenkins VA. Talking about risk in the context of GEomic profiling tests (TARGET) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-11-04.
Abstract P4-12-13: Comparative analysis of costs between subcutaneous formulation of trastuzumab versus intravenous formulation from the perspective of the Instituto Oncológico Nacional of Panamá from January to December 2016
Authors: Martin C , Alcedo J , Araúz E 
Published: February 2018

Abstract
Objective: Because there is actually availability of both Intravenous(IV) and subcutaneous(SC) formulation of Trastuzumab for use in the public sector in the Instituto Oncológico Nacional and knowing that de SC formulation has been compared previously with the IV in term of efficacy in and it was not inferior and also is prefered by patients it is useful to count with a study of costs minimization that can determine what formulation results more convenient to maintain available for use in the Instituto Oncológico Nacional based on the criteria of efficiency of the intervention.(1)(2)
Methodology: This is a cost minimization study considering the cost of the treatment, the supplies and the time utilized by Pharmacy and Nursing to prepare and administer it.
Results: In relation to the cost of the treatment the SC presentation has a cost per patient 17% less than the IV presentation in relation to the cost that offers the Pharmaceutical company, considering a weight of 70 kg per patient ( IV presentation) and a fixed dose of 600 mg(SC presentation). Considering the supplies utilized by Pharmacy and Nursing to prepare and administer the IV and SC presentation, the SC presentation requires less supplies and this facilitates its administration and decreases the cost of the treatement in a 67%. In terms of time invested in preparing and administering the IV and the SC formulation, accounting for both, nursing and pharmacy, it is observed that the SC formulation requires less amount of time than the IV formulation and this decreases the cost of the treatment in a 90%.
Analisis of Saving by Use of SC Trastuzumab vs IV TrastuzumabItemSC TrastuzumabIV Trastuzumab% SavingTreatment10,578,0538,826,89417%Nursing Supplies18,9662,50387%Pharmacy Supplies31,98217,02047%Nursing Time71,7916,33591%Pharmacy Time2,28971669%Total anual cost10703081885346717%
Conclusion: With the use of the SC formulation of Trastuzumab there is combined savings of 17%, that represents anually 5985 USD per patient based on a treatment of 18 cycles of Traztuzumab per year, that results in a total saving of 1,84 million USD per year.
(1) Pivot et al. Lancet Oncol 2013 Sep;14(10):962-70.
(2)Ismael G et al. Lancet Oncol 2012 Sep;13(9):869-78
Citation Format: Martin C, Alcedo J, Araúz E. Comparative analysis of costs between subcutaneous formulation of trastuzumab versus intravenous formulation from the perspective of the Instituto Oncológico Nacional of Panamá from January to December 2016 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-13.