To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. We assessed model calibration by evaluating observed versus predicted mutations and attribute diagrams, and model discrimination using areas under the receiver operating characteristic curves.Both models were well-calibrated within each racial/ethnic group, with some exceptions. Multiple imputation with missing data indicators. Plevritis, S. K., Munoz, D. n., Kurian, A. W., Stout, N. K., Alagoz, O. n., Near, A. M., Lee, S. J., van den Broek, J. J., Huang, X. n., Schechter, C. B., Sprague, B. L., Song, J. n., de Koning, H. J., Trentham-Dietz, A. n., van Ravesteyn, N. T., Gangnon, R. n., Chandler, Y. n., Li, Y. n., Xu, C. n., Ergun, M. A., Huang, H. n., Berry, D. A., Mandelblatt, J. S. Comparative effectiveness of nab-paclitaxel versus paclitaxel monotherapy as first-line treatment of metastatic triple-negative breast cancer in US clinical practice. Ductal lavage was attempted in any duct identifiable with a catheter.Ducts were successfully catheterized in 60 of 75 patients (80%). These results suggest disparities in the care of patients from SGM groups and warrant further study to inform interventions. We used simulation modeling to fill these gaps.We simulated women eligible for TAILORx using joint distributions of patient and tumor characteristics and RS from TAILORx data; treatment effects by RS from other trials; and competing mortality from the Surveillance, Epidemiology, and End Results program database. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. However, only a small proportion of their variance is explained by identified genetic variants.We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia.We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Many patients (78%-82%) with PGVs met criteria for germline follow-up testing, and 8.1% of PGVs were missed by tumor sequencing. Afghahi, A., Mathur, M., Seto, T., Desai, M., Kenkare, P., Horst, K. C., Das, A. K., Thompson, C. A., Luft, H. S., Yu, P., Gomez, S., Low, Y., Shah, N. H., Kurian, A. W., Sledge, G. W. Concerns about cancer risk and experiences with genetic testing in a diverse population of patients with breast cancer. Notably, failing to impute cases with missing receptor status leads to overestimation of survival because those with missing receptor status tend to have worse prognostic features. Women with HR-negative first tumors have nearly a 10-fold elevated risk of developing HR-negative second tumors, compared with the general population. For more information, please contact Pei-Jen Chang, 650-725-0866. Results were adjusted for multiple hypothesis testing. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. Vigen, C., Gomez, S. L., Sposto, R., Lu, Y., Kwan, M., John, E., Monroe, K., Keegan, T. H., Shariff-Marco, S., Kurian, A. W. Oncoshare: lessons learned from building an integrated multi-institutional database for comparative effectiveness research. Exhaustive preoperative stomach evaluation was normal in each case, and the stomach and adjacent lymph nodes appeared normal at surgery. For more information, please contact Mary Chen, (650) 723 - 8686. Unilateral mastectomy was associated with higher mortality than were the other 2 surgical options. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Morrow, M. n., Abrahamse, P. n., Hofer, T. P., Ward, K. C., Hamilton, A. S., Kurian, A. W., Katz, S. J., Jagsi, R. n. NCCN Guidelines (R) Insights Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017 Featured Updates to the NCCN Guidelines. We used publicly available in silico DNase I and ChIP-seq data with invitro reporter gene and CRISPR assays to annotate signals 2 and 3. View details for DOI 10.1093/jamia/ocw161. Little is known about its long-term performance in a racially/ethnically diverse population.The Women's Health Initiative study enrolled postmenopausal women from 1993-1998. We analyzed the care of patients with breast cancer and mapped Common Procedural Terminology (CPT) codes to the corresponding cost conversion factor and date in the CMS Medicare fee schedule. All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Clinical guidelines recommend breast-conserving surgery (BCS) with radiation as a viable alternative to mastectomy for treatment of early-stage breast cancer. For all-cause mortality, even stronger BMI and WHR associations were observed. 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Responses were merged with SEER data. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview.Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China.A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Along with educational level and use of internet support groups, uncertain results on genomic testing predicted second opinion use. A., Sirota, M., Kenkare, P., Thompson, C. A., Yu, P. P., Gomez, S. L., Sledge, G. W., Kurian, A. W., Shah, N. H. Protective Effects of Statins in Cancer: Should They Be Prescribed for High-Risk Patients? Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The Trial Assigning Individualized Options for Treatment (TAILORx) found chemotherapy could be omitted in many women with hormone receptor-positive, HER2-negative, node-negative breast cancer and 21-gene recurrence scores (RS) 11-25, but left unanswered questions. We propose an efficient natural language processing approach for inferring the BI-RADS final assessment categories by analyzing only the mammogram findings reported by the mammographer in narrative form. Our objective was to characterize trends in annual surveillance mammography participation among women with a personal history of breast cancer over a 13-year period.We examined annual surveillance mammography participation from 2004 to 2016 in a nationwide sample of commercially insured women with prior breast cancer. Afghahi, A., Forgo, E., Mitani, A. Ruth, K. S., Day, F. R., Hussain, J., Martnez-Marchal, A., Aiken, C. E., Azad, A., Thompson, D. J., Knoblochova, L., Abe, H., Tarry-Adkins, J. L., Gonzalez, J. M., Fontanillas, P., Claringbould, A., Bakker, O. Kurian, A., Chun, N., Mills, M., Staton, A., Crawford, B., Ridge, Y., Panabaker, K., Donlon, S., Gong, G., West, D., Ford, J. CDH1 truncating mutations in the E-cadherin gene - An indication for total gastrectomy to treat hereditary diffuse gastric cancer. We found that the vast majority of respondents (94%, 127/135) ordered an HCP for patients rather than single-gene tests to assess hereditary cancer predisposition. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Among established breast cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53), we evaluated PV prevalence according to family history extent and breast cancer subtype. Quantitative image features were extracted to characterize tumor morphology, intra-tumor heterogeneity of contrast agent wash-in/wash-out patterns, and tumor-surrounding parenchyma enhancement. We assessed trends in NAC use and surgical procedures in California from January 1, 1998 to December 31, 2012 using statewide population-based cancer registry data.A total of 236,797 females diagnosed with stage I-III BC were studied. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery.We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. Kwan, M. L., John, E. M., Caan, B. J., Lee, V. S., Bernstein, L., Cheng, I., Gomez, S. L., Henderson, B. E., Keegan, T. H., Kurian, A. W., Lu, Y., Monroe, K. R., Roh, J. M., Shariff-Marco, S., Sposto, R., Vigen, C., Wu, A. H. The California Breast Cancer Survivorship Consortium (CBCSC): prognostic factors associated with racial/ethnic differences in breast cancer survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP, View details for DOI 10.1186/s13058-021-01450-7. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic.We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No. Monoclonal
Results Overall, 47.4% did not get tested, 40.7% tested negative, 7.4% had a variant of uncertain significance only, and 4.5% had a pathogenic mutation. Respondents often recalled clinicians informing them about inheritance patterns (65%; 95% CI, 62% to 67%), surgical implications (65%; 95% CI, 63% to 68%), and other cancer risks (66%; 95% CI, 63% to 68%) but less often that results could have potential implications for clinical trial eligibility (38%; 95% CI, 36% to 42%) or targeted therapies (14%; 95% CI, 12% to 16%). This was associated with poor therapy response, early relapse and death. Patients indicated that financial toxicity remains common: 21.5% of white patients and 22.5% of Asian patients had to cut down spending on food, as did 45.2% of black and 35.8% of Latina patients. Mantz, A. Little is known about differences in risk for second primary breast cancers related to the estrogen and progesterone receptor (hormone receptor [HR]) status of the first tumor.We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for contralateral primary breast cancers among 4927 women diagnosed with a first breast cancer between January 1, 1992, and December 31, 2004, using the National Cancer Institute's Surveillance, Epidemiology, and End Results database.For women whose first breast tumors were HR positive, risk of contralateral primary breast cancer was elevated, compared with the general population, adjusted for age, race, and calendar year (SIR = 2.22, 95% CI = 2.15 to 2.29, absolute risk [AR] = 13 cases per 10 000 person-years [PY]), and was not related to the HR status of the second tumor. View details for DOI 10.1200/CCI.19.00034. He is responsible for leading software development and transitioning the company's technology to the Cloud. A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. The base case used treatment efficacy measures reported in the randomized clinical trials of AT. Yet, Asian Americans are more likely than other groups to have mastectomy or omit radiation after BCS.We applied polytomous logistic regression and recursive partitioning to analyze factors associated with mastectomy, or BCS without radiation, among 20,987 California Asian Americans diagnosed with stage 0 to II breast cancer from 1990 to 2007.The percentage receiving mastectomy ranged from 40% among U.S.-born Chinese to 58% among foreign-born Vietnamese. View details for DOI 10.1016/j.jbi.2019.103137. We discuss events leading to the wider availability of commercialized multiple-gene germline panel testing, the recent data that support using this powerful tool to improve cancer risk assessment and reduction strategies, and remaining challenges to clinical optimization of this new genetic technology. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. At a friends wedding, Thomas met his present wife, Allison, who initially ignored him. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer.To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer.For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. Ling, A. Y., Kurian, A. W., Caswell-Jin, J. L., Sledge, G. W., Shah, N. H., Tamang, S. R. Can precision medicine help achieve the goal of reducing care when the risks exceed the benefits? This is a 3 arm Phase 3 study to evaluate the safety and efficacy of the addition of
Predictors of second opinion use included college education vs less education (odds ratio [OR], 1.85; 95% CI, 1.24-2.75), frequent use of internet-based support groups (OR, 2.15; 95% CI, 1.12-4.11), an intermediate result on the 21-gene recurrence score assay (OR, 1.85; 95% CI, 1.11-3.09), and a variant of uncertain significance on hereditary cancer genetic testing (OR, 3.24; 95% CI, 1.09-9.59). View details for DOI 10.1200/JCO.20.02785. Next-generation sequencing promises major advancements in precision medicine but faces considerable challenges with insurance coverage. Among the 451 probands analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. Care partners preferred to focus primarily on the patient's health and not their own. Compared to non-Hispanic White women, Korean [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5-2.2], Filipina (OR = 1.3, 95% CI = 1.2-1.5), Vietnamese (OR = 1.3, 95% CI = 1.1-1.6), and Chinese (OR = 1.1, 95% CI = 1.0-1.3) women had a significantly increased risk of being diagnosed with HER2-positive breast cancer subtypes after adjusting for age, stage, grade, socioeconomic status, histology, diagnosis year, nativity, and hospital ownership status. Gene burden tests detected the strongest association for deletions in BRCA1 (P=3.7E-18). PURPOSE: This clinical trial studies factors influencing decision-making about the use of
For more information, please contact Meredith Mills, (650) 724 - 5223. Surgery after initial lumpectomy to obtain more widely clear margins is common and may lead to mastectomy.To describe surgeons' approach to surgical margins for invasive breast cancer, and changes in postlumpectomy surgery rates, and final surgical treatment following a 2014 consensus statement endorsing a margin of "no ink on tumor. Early user testing demonstrated ease of use and app feasibility.TOGETHERCare, a novel mobile app, was developed with user input to track the care partner's health and report on survivor symptoms during home care. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. "126 (46.2%) of survivors were "good sleepers," 147 (53.8%) were "bad sleepers." Actual 10-year risk of distant recurrence after treatment was based on clinical factors for women with DCIS & low-risk invasive cancer (Stg 1A, ER+, HER2-, Gr 1-2). Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. More than one third of identified pathogenic variants were not clinically anticipated. One-year adjuvant trastuzumab (AT) therapy, with or without anthracyclines, increases disease-free and overall survival in early-stage HER2/neu-positive breast cancer. However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. To examine chemotherapy indications for germline pathogenic variant (PV) carriers, we linked results of germline testing to Georgia and California Surveillance, Epidemiology, and End Results registry records, including 21-gene recurrence score (RS) results, for breast cancer patients diagnosed in 2013-2017. He completed his residency in internal medicine and completed an adult cardiology fellowship at Henry Ford Hospital in Detroit, MI. Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants: A Comparative Modeling Analysis. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging
View details for DOI 10.1200/JCO.21.00651. induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in
Across racial/ethnic groups, nearly half of all luminal breast cancers occur after age 70.These absolute risk estimates may inform health policy and resource planning across diverse populations, and can help patients and physicians weigh the probabilities of developing specific breast cancer subtypes against competing health risks. Schackmann, E. A., Munoz, D. F., Mills, M. A., Plevritis, S. K., Kurian, A. W. Information technology interventions to improve cancer care: a report from the American Society of Clinical Oncology Quality Care Symposium. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. We examined the contribution of variables in a previously reported Cox regression baseline model plus additional contextual, physical activity, body size, and comorbidity variables to the racial/ethnic disparity in breast cancer-specific mortality.The cohort comprised 12,098 women. These patients received germline testing between January 5, 2015, and January 31, 2020, although most (81% of patients) received testing between January 2, 2018, and January 31, 2020.The prevalence of pathogenic germline variants (PGVs) was calculated by gene, cancer type, and age at diagnosis. Now you may have guessed thatThomas Kurian net worth is not less than millions of dollars. Chemotherapy details were extracted from SEER text fields completed by registrars. A., Chung, W. K., Milne, R. L., Whittemore, A. S., Buchsbaum, R. n., Liao, Y. n., Zeinomar, N. n., Dite, G. S., Southey, M. C., Goldgar, D. n., Giles, G. G., Kurian, A. W., Andrulis, I. L., John, E. M., Daly, M. B., Buys, S. S., Phillips, K. A., Hopper, J. L., Terry, M. B. Americans, lower neighborhood SES was associated with higher mortality than were the other 2 surgical.... Crispr assays to annotate signals 2 and 3 non-Hispanic White PV carriers the company & # x27 ; technology! 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