The magnitude of breast and ovarian cancer risk associated with many clinically tested genes, and independent of family cancer history, remains to be quantified.We queried a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene (APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CHEK2, MLH2, MSH2, MSH6, MUTYH, NBN, P14ARF, P16, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53) next-generation sequencing panel. To quantify the influence of RS assay on changing chemotherapy plans in a general practice setting using causal inference methods.We surveyed 3880 newly diagnosed breast cancer patients in Los Angeles and Georgia in 2013-14. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. Risk of all histologic types was unassociated with age at menarche, age at menopause, a history of infertility, noncontraceptive estrogen use, and alcohol consumption.The most important modifiers of ovarian cancer risk (parity and oral contraceptive use) showed similar associations across the histologies. To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Jagsi, R. n., Ward, K. C., Abrahamse, P. H., Wallner, L. P., Kurian, A. W., Hamilton, A. S., Katz, S. J., Hawley, S. T. Association of Attending Surgeon With Variation in the Receipt of Genetic Testing After Diagnosis of Breast Cancer. Fourteen participants carried 15 pathogenic variants, warranting a possible change in care; they were invited for targeted screening recommendations, enabling early detection and removal of a tubular adenoma by colonoscopy. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). In conclusion, the use of laboratories with payment assistance programs reduces barriers to NGS panel testing among diverse populations. Both were accepted to the prestigious IIT Madras. He reports to . Johnson, N. n., Maguire, S. n., Morra, A. n., Kapoor, P. M., Tomczyk, K. n., Jones, M. E., Schoemaker, M. J., Gilham, C. n., Bolla, M. K., Wang, Q. n., Dennis, J. n., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H. n., Antonenkova, N. N., Arndt, V. n., Aronson, K. J., Augustinsson, A. n., Baynes, C. n., Freeman, L. E., Beckmann, M. W., Benitez, J. n., Bermisheva, M. n., Blomqvist, C. n., Boeckx, B. n., Bogdanova, N. V., Bojesen, S. E., Brauch, H. n., Brenner, H. n., Burwinkel, B. n., Campa, D. n., Canzian, F. n., Castelao, J. E., Chanock, S. J., Chenevix-Trench, G. n., Clarke, C. L., Conroy, D. M., Couch, F. J., Cox, A. n., Cross, S. S., Czene, K. n., Drk, T. n., Eliassen, A. H., Engel, C. n., Evans, D. G., Fasching, P. A., Figueroa, J. n., Floris, G. n., Flyger, H. n., Gago-Dominguez, M. n., Gapstur, S. M., Garca-Closas, M. n., Gaudet, M. M., Giles, G. G., Goldberg, M. S., Gonzlez-Neira, A. n., Gunel, P. n., Hahnen, E. n., Haiman, C. A., Hkansson, N. n., Hall, P. n., Hamann, U. n., Harrington, P. A., Hart, S. N., Hooning, M. J., Hopper, J. L., Howell, A. n., Hunter, D. J., Jager, A. n., Jakubowska, A. n., John, E. M., Kaaks, R. n., Keeman, R. n., Khusnutdinova, E. n., Kitahara, C. M., Kosma, V. M., Koutros, S. n., Kraft, P. n., Kristensen, V. N., Kurian, A. W., Lambrechts, D. n., Le Marchand, L. n., Linet, M. n., Lubiski, J. n., Mannermaa, A. n., Manoukian, S. n., Margolin, S. n., Martens, J. W., Mavroudis, D. n., Mayes, R. n., Meindl, A. n., Milne, R. L., Neuhausen, S. L., Nevanlinna, H. n., Newman, W. G., Nielsen, S. F., Nordestgaard, B. G., Obi, N. n., Olshan, A. F., Olson, J. E., Olsson, H. n., Orban, E. n., Park-Simon, T. W., Peterlongo, P. n., Plaseska-Karanfilska, D. n., Pylks, K. n., Rennert, G. n., Rennert, H. S., Ruddy, K. J., Saloustros, E. n., Sandler, D. P., Sawyer, E. J., Schmutzler, R. K., Scott, C. n., Shu, X. O., Simard, J. n., Smichkoska, S. n., Sohn, C. n., Southey, M. C., Spinelli, J. J., Stone, J. n., Tamimi, R. M., Taylor, J. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). Multiple phase 1 and 2 prevention studies of statins for breast cancer risk reduction are ongoing. Here, we propose a multiple-ancestry PRS (MA-PRS) that addresses these issues and may be useful in the development of equitable PRSs across other cancers and common diseases.Women referred for hereditary cancer testing were divided into consecutive cohorts for development (n = 189,230) and for independent validation (n = 89,126). Petkov, V., Kurian, A. W., Jakubowski, D. M., Shak, S. Abstract P6-08-07: Polygenic breast cancer risk modification in carriers of high and intermediate risk gene mutations. The Accuracy of BRCA1/2 Mutation Prediction Models in Different Ethnicity and Gender: Experience in a Chinese Cohort, Kwong, A., Wong, C., Suen, D., Choi, C., Wong, C., Law, F., Kurian, A. W., et al, A High Percentage of Triple Negative Tumors Present as Palpable Masses. Breast cancer risk was marginally increased among foreign-born women (OR=1.40, 95% CI=0.97-2.03) and two-fold among foreign-born Chinese women (OR=2.16, 95% CI=1.21-3.88). The type of risk-management options planned to be taken up in the future (i.e., beyond the end of the study) and the potential impact of personalised risk estimates on women's psychosocial health will be collected as secondary-outcome measures. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Given the poor prognosis and high treatment costs of HER2-positive breast cancer, our results have implications for healthcare resource utilization, cancer biology, and clinical care. Studies have demonstrated that engaging cancer survivors and their care partners through technology-enabled structured symptom collection has several benefits. Here, weestablish an invitro model for BRCA2-crisis that demonstrates chromatin remodeling and activation of an NF-B survival pathway in response to transient BRCA2 depletion. Thomas Kurian married a woman from Boston in typical style. 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. View details for DOI 10.1200/JCO.2010.34.4440, View details for PubMedCentralID PMC3236651. Fifty-four percent were non-Latina Whites, 17% African Americans, 17% Latinas, and 12% Asian Americans. Most NAC recipients (68.4%) had mastectomies, and 14.3% of them underwent BLM. The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. Women with mutations in the BRCA1 or BRCA2 cancer susceptibility genes face unique choices regarding management of their high risk for breast and ovarian cancer that impact their reproductive options. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TNBC or HGSOC is unknown.To assess the potential association between white blood cell BRCA1 promoter methylation and subsequent risk of incident TNBC and HGSOC.This case-control study included women who were participating in the Women's Health Initiative study who had not received a diagnosis of either breast or ovarian cancer before study entrance. Petkov, V., Howlader, N., Cronin, K., Kurian, A. W., Penberthy, L. Magnitude of invasive breast cancer risk associated with mutations detected by multiple-gene germline sequencing in 95,561 women. We identified de novo MBC patients from CCR and extracted information on distant recurrences from patient notes in EMR. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival. Three months post genetic testing, communication of results was very high; 30% reported a family member underwent genetic testing. Multivariate models evaluated correlates of missing work for >1 month and stopping work altogether versus missing work for 1 month.In this diverse sample, most patients (62%) underwent lumpectomy; 16% underwent unilateral mastectomy (8% with reconstruction); and 23% underwent bilateral mastectomy (19% with reconstruction). Financial toxicity was "mild" overall (COST M=26.11, SD=11.14); 32% worried about cancer-related financial problems (quite a bit/very much; item-level analysis). By integrating complementary data from EMRs and population-based registries, a more comprehensive understanding of breast cancer care and factors that drive treatment use was obtained. : CRD42020134276). For more information, please contact Pei-Jen Chang, (650) 725 - 0866. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiation nor chemotherapy (HR=2.11, 95% CI=1.32-3.36); no increased risk was observed among those who received both treatments (HR=1.13, 95% CI= 0.70-1.84) (P interaction= 0.03). View details for DOI 10.1002/pon.5763 The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.From EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. BRCA1/2 We identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during 2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC within 12 months of diagnosis. However, these drugs are associated with side effects. A 73-gene signature based on the tumor profiles in TCGA achieved good association with the tumor-adjacent parenchymal image feature (R(2) = 0.873), which stratified patients into groups regarding recurrence-free survival (log-rank P = .029) and overall survival (log-rank P = .042) in an independent TCGA cohort. Mean age was 34 years; 66% were BRCA1 mutation carriers and 34% were BRCA2 mutation carriers. Long-term sustainability of laboratory payment assistance programs was a major concern; safety-net clinics were particularly concerned about access to testing without such programs. [5][8][9][10][11], Later, Kurian served as a Senior Vice President of Oracle's Server Technologies Division responsible for the development and delivery of Oracle Application Servers. In the past decade, there has been a surge both in genetic testing technology and in patient access to such testing. A., Teo, S. H., Teras, L. R., Toland, A. E., Tollenaar, R. A., Torres, D., Torres-Meja, G., Troester, M. A., Truong, T., Vachon, C. M., Vijai, J., Weinberg, C. R., Wendt, C., Winqvist, R., Wolk, A., Wu, A. H., Yamaji, T., Yang, X. R., Yu, J. C., Zheng, W., Ziogas, A., Ziv, E., Dunning, A. M., Easton, D. F., Hemingway, H., Hamann, U., Kuchenbaecker, K. B. There was no evidence that the BMI or weight associations differed by underlying familial risk (P>0.2). View details for DOI 10.1093/jnci/djab097. efficacy of the combination will also be collected. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Gupta, T., Purington, N., Liu, M., Han, S., Sledge, G., Schapira, L., Kurian, A. W. The effect of COVID-19 on telehealth: next steps in a post-pandemic life. Cox proportional hazards models provided estimates of the relative hazard ratio for mortality from all causes, breast cancer, and causes other than breast cancer associated with recent recreational physical activity (i.e., in the 10 years before diagnosis). [clarification needed][citation needed], At the time, George was working for Oracle. Why did Google Cloud CEO Diane Greene Quit? Claims data track patients, but lack clinical detail. For women aged 20-39years, 5-year risk performed better than lifetime risk from birth. CDH1 mutations are an indication for total gastrectomy in these patients. Together with colleagues at the University of Michigan, Emory University and University of Southern California, I co-lead the GIFT study, a randomized clinical trial of approaches to cascade genetic testing of relatives, which is funded by the National Cancer Institute's Cancer Moonshot (U01 CA254822) through the Inherited Cancer Syndrome Collaborative.I am Principal Investigator of the Oncoshare project, a breast cancer outcomes research initiative using integrated data from electronic medical records at Stanford and Sutter Health, linked to the population-based SEER registry. However, few data exist for racial/ethnic groups other than non-Latina whites. Cause-specific proportional hazards models estimated SPLC risk. View details for DOI 10.1038/s41598-021-99409-3, Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Those who endorsed a maladaptive mindset (Cancer is a Catastrophe) reported lower health-related quality of life (HRQOL) compared with those who did not hold this belief (p < .001). Breast cancer patients' misunderstanding of their systemic cancer recurrence risk has consequences on decision-making and quality of life. 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. After controlling for patient and tumor characteristics, second opinion use was not associated with chemotherapy receipt (OR, 1.04; 95% CI, 0.71-1.52).Second opinion use was low (<10%) among patients with early-stage breast cancer, and high decision satisfaction regardless of second opinion use suggests little unmet demand. Our final MBC classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.917, with sensitivity 0.861, specificity 0.878, and accuracy 0.870.To enable population-based research on MBC, we developed a framework for retrospective case detection combining EMR and CCR data. Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. Wapnir, I., Kingham, K., Mills, M., Ford, J., Kurian, A. View details for DOI 10.1097/01.sla.0000254370.29893.e4. Factors associated with reporting higher toxicity severity included receipt of chemotherapy (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 2.0-2.5), receipt of both chemotherapy and radiotherapy (OR, 1.3; 95% CI, 1.0-1.7), and Latina ethnicity (OR vs whites: 1.3; 95% CI, 1.1-1.5). [3], Upon completing her fellowship, Kurian accepted a research scholar position supported by a Building Interdisciplinary Research Careers in Women's Health K12 award. Prevalence and consequences of second opinions from medical oncologists for early-stage breast cancer: Results from the iCanCare study. Performance of BRCA1/2 mutation prediction models in Asian Americans. Thomas Kurian is an Indian-American business executive and Chief Executive Officer of Google Cloud since 2019. [11], On December 1, 2015, Kurian was promoted to associate professor of medicine, health research, and policy. We used inverse propensity weighting and multiple imputations to derive complete information for each patient about treatment status with and without testing.A half of the 1545 women eligible for testing (ER+ or PR+, HER2-, and stage I-II) received RS. Allison, K. H., Jensen, K., West, R., Clarke, C. A., Gomez, S. L., Kurian, A. W. Beyond Barriers: Systemic Constraints Limiting Sexual Health Care for Breast Cancer Survivors. 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. For BRCA1 and BRCA2 pathogenic variant carriers who underwent RRSO at age 40 years, the cause-specific cumulative risk of breast cancer was 49.7% (95% CI,40.0-60.3) and 52.7% (95% CI,47.9-58.7) by age 70 years, respectively, compared with 61.0% (95% CI,56.7-66.0) and 54.0% (95% CI,49.3-60.1), respectively, for women without RRSO.Although the primary indication for RRSO is the prevention of ovarian cancer, it is also critical to assess its association with breast cancer risk in order to guide clinical decision-making about RRSO use and timing. Ellisen, L., Kurian, A. W., Desmond, A. J., et al. Thomas Kurian has spent nearly 20 years at Oracle. Dr. Allison W. Kurian is an oncologist in Palo Alto, California and is affiliated with Stanford Health Care-Stanford Hospital. A., Schackmann, E. A., Wapnir, I., Carlson, R. W., Sparano, J. Adding BMI or height to weight did not improve fit (AIC=0.90 and 0.83, respectively; both P=0.3). Stanford is currently not accepting patients for this trial. Parikh, D. A., Dickerson, J. C., Kurian, A. W. Combined associations of a polygenic risk score and classical risk factors with breast cancer risk. These results may inform clinical decision-making about ET, and reassure patients who have bothersome symptoms on AIs that they are unlikely to develop worse comorbidities if they switch to tamoxifen. Information regarding NAC, adjuvant chemotherapy (aCT), breast conserving surgery (BCS), bilateral mastectomy (BLM), and unilateral mastectomy (ULM) was abstracted from the medical records. Future studies should prospectively evaluate larger numbers of high-risk women via multivariate analysis, to determine characteristics associated with preference for breast screening vs. PM. We tested whether the use of RS seems to guide chemotherapy receipt across different cancer care settings.We developed a retrospective cohort of patients with breast cancer by using electronic medical record data from Stanford University (hereafter University) and Palo Alto Medical Foundation (hereafter Community) linked with demographic and staging data from the California Cancer Registry and RS results from the testing laboratory (Genomic Health Inc., Redwood City, CA). These results suggest a potential benefit of genetic counseling and testing for pathogenic variants in less familiar genes. Caswell-Jin, J. L., Zimmer, A. D., Stedden, W., Kingham, K. E., Zhou, A. Y., Kurian, A. W. Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer. BRCA1 mutations were more common among whites (67 vs. 42%, p=0.02), and BRCA2 mutations among Asians (58 vs. 37%, p=0.04). For select women at increased risk for breast cancer, preventive medication can greatly decrease risk and is vastly underutilized. Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Kidd, J., Evans, B., Brown, K., Mills, M., Ma, C., Hong, C., McDonnell, K. J., Ladabaum, U., Ford, J. M., Gruber, S. B. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Background:The role of comorbidities in survival of breast cancer patients has not been well studied, particularly in non-white populations. Along with educational level and use of internet support groups, uncertain results on genomic testing predicted second opinion use. Kurian, A. W., Ward, K. C., Abrahamse, P., Hamilton, A. S., Deapen, D., Morrow, M., Katz, S. J. Temporal analyses revealed important trends: the possible contribution of the CMS NCD to a faster pace of coverage adoption, the interdependence in coverage timing among BlueCross BlueShield members, the impact of using a third-party policy on coverage timing, and the importance of small payers in early adoption. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). steroidal aromatase inhibitors (NSAI). Knowledge of BRCA mutations in Chinese populations is still largely unknown. White, D. P., Kurian, A. W., Stevens, J. L., Liu, B., Brest, A. E., Petkov, V. I. A survival analysis approach was used that was designed specifically to assess the time-varying association of RRSO with breast cancer risk and accounting for other potential biases. Kurian, A. W., Ward, K. C., Howlader, N., Deapen, D., Hamilton, A. S., Mariotto, A., Miller, D., Penberthy, L. S., Katz, S. J. Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative. Relative risks were lower after BLM (hazard ratio [HR], 0.10; 95% CI, 0.07-0.14) and higher after ULM (HR, 1.07; 95% CI, 1.02-1.13) versus BCT. View details for DOI 10.6004/jnccn.2018.7266 Race and ethnicity have been shown to affect quality of cancer care, and patients with low English proficiency (LEP) have increased risk for serious adverse events. Out of the total compensation, he received $800,000 as a salary, $3,612,553 as a bonus, $69,380,000 as stock options, and $7,337 from other types of compensation. Breast Cancer Risk Reduction, Version 2.2015. We analyzed data using descriptive statistics, chi2 and t tests.RESULTS: Three hundred twelve people with cancer participated and represented 38 states. Pollom, E. L., Qian, Y., Chin, A. L., Dirbas, F. M., Asch, S. M., Kurian, A. W., Horst, K. C., Tsai, C. Cancer Risk Estimates for Study of Multiple-Gene Testing After Diagnosis of Breast Cancer Reply, Can We Use Survival Data from Cancer Registries to Learn about Disease Recurrence? However, each patient (6 of 6, 100%) was found to have multiple foci of T1 invasive diffuse gastric adenocarcinoma (pure signet-ring cell type). Shariff-Marco, S. n., Ellis, L. n., Yang, J. n., Koo, J. n., John, E. M., Keegan, T. H., Cheng, I. n., Monroe, K. R., Vigen, C. n., Kwan, M. L., Lu, Y. n., Bernstein, L. n., Wu, A. H., Gomez, S. L., Kurian, A. W. Abstract IA50: Genetic testing, treatment and mortality after diagnosis of breast cancer or ovarian cancer: The SEER-GeneLINK Initiative, Health Disparities in Germline Genetic Testing for Cancer Susceptibility. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. This approach may be adaptable to other cancer sites and could help to unlock the potential of EMRs for research on real-world cancer outcomes. Katz, S. J., Hawley, S. T., Bondarenko, I. n., Jagsi, R. n., Ward, K. C., Hofer, T. P., Kurian, A. W. Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer. High-penetrance autosomal dominant cancer susceptibility genes such as BRCA2 and MEN1 result in specific patterns of cancers in individuals who inherit germline mutations. We built a gene expression-based classifier of imaging subtypes and tested their prognostic significance in five additional cohorts with publically available gene expression data but without imaging data (n=1160).Three distinct imaging subtypes, i.e., homogeneous intratumoral enhancing, minimal parenchymal enhancing, and prominent parenchymal enhancing, were identified and validated. 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