We identified 1886 MBC patients, 512 (27.1%) of whom were de novo MBC patients and 1374 (72.9%) were recurrent MBC patients. The proposed hybrid method integrates semantic term embedding with distributional semantics, producing a context-aware vector representation of unstructured mammography reports. A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer. Screening with contrast-enhanced breast magnetic resonance imaging (MRI) detects cancer earlier but increases costs and results in more false-positive scans.To evaluate the cost-effectiveness of screening BRCA1/2 mutation carriers with mammography plus breast MRI compared with mammography alone.A computer model that simulates the life histories of individual BRCA1/2 mutation carriers, incorporating the effects of mammographic and MRI screening was used. This was associated with poor therapy response, early relapse and death. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model-estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and all-cause mortality. Thirty-one successfully catheterized patients [51.6%, 95% confidence interval (39.4-63.9%)] had non-fluid-yielding ducts only. He was an Arjay Miller Scholar. Mean hazard ratios SD, and DRFS rates are reported from 1000 simulations.The simulation results closely replicated TAILORx findings, with 75% of simulated trials showing noninferiority forchemotherapy omission. Non-college-educated Black women had lower odds of guideline-concordant care (aOR (CI) = 0.29 (0.12-0.67)) vs. college-educated White women. We know little about whether it matters which oncologist a breast cancer patient sees with regard to receipt of chemotherapy. George Kurian, who grew up in Bengaluru, has just been appointed CEO of the $6-billion, US-based computer storage and data management company NetApp.As remarkable as that is, the more remarkable part of this story is the near identical journeys that George and his twin brother Thomas Kurian, president of Oracle, have had. Adopters were less likely to be BlueCross BlueShield members (P < .05) and more likely to use a third-party policy (P < .001). 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. Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Each was staged as T1N0M0. Women were included who were aged <80 years at enrollment with no prior breast cancer or mastectomy and with data required for IBIS/Tyrer-Cuzick calculation (weight; height; ages at menarche, first birth, and menopause; menopausal hormone therapy use; and family history of breast or ovarian cancer). A., Korde, L. A., Kounalakis, N., Krontiras, H., Kumar, S., Kurian, A., Laronga, C., Layman, R. M., Loftus, L. S., Mahoney, M. C., Merajver, S. D., Meszoely, I. M., Mortimer, J., Newman, L., Pritchard, E., Pruthi, S., Seewaldt, V., Specht, M. C., Visvanathan, K., Wallace, A., Bergman, M. A., Kumar, R. History of Recreational Physical Activity and Survival After Breast Cancer The California Breast Cancer Survivorship Consortium. Afghahi, A., Mitani, A., Desai, M., Yu, P., De Bruin, M. A., Seto, T., Olson, C., Kenkare, P., Gomez, S., Das, A. K., Luft, H. S., Sing, A. P., Kurian, A. W. Breast cancer treatment across health care systems: linking electronic medical records and state registry data to enable outcomes research. View details for DOI 10.1200/JCO.2006.06.3081, View details for Web of Science ID 000244384000006. Cancers were confirmed after central medical record review. Ultimately, larger replication studies are needed to confirm the identified associations. 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. Effect sizes, expressed as standardized odds ratios (ORs) with 95% CIs, were assessed for carriers of PVs in each gene as well as for noncarriers.The median age at hereditary cancer testing of the population was 48 years (range, 18-84 years); there were 141160 noncarriers in addition to carriers of BRCA1 (n=2249), BRCA2 (n=2638), CHEK2 (n=2564), ATM (n=1445), and PALB2 (n=906) PVs included in the analysis. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Clinicians influence testing decisions and should inform patients about legal protections and treatment implications. She is also a clinically active oncologist, treating patients diagnosed with breast cancer. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI= 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI= 0.622-0.649). This study evaluated breast and gynecologic cancer patients' subjective experiences of financial toxicity and associations with distress and quality of life (QOL).A cross-sectional survey study included measures of financial toxicity (Comprehensive Score for financial Toxicity [COST] Version 2), distress (Patient Health Questionnaire [PHQ-4]), and QOL (Functional Assessment of Cancer Therapy [FACT-G]). Hall, M. J., Hughes, E., Kucera, M., Kidd, J., Bernhisel, R., Hullinger, B., Slavin, T., Kurian, A. W. Simulation modeling as a tool to support clinical guidelines and care for breast cancer prevention and early detection in high-risk women. Preliminary information about the His first executive role was as Vice President of Oracle's e-Business division. The most influential variables were related to disease characteristics, neighborhood socioeconomic status, and smoking status at diagnosis. Subjects will be assigned to The role of prophylactic versus therapeutic gastrectomy for HDGC was studied prospectively.Eighteen consecutive patients with CDH1 mutations and positive family history were studied prospectively, including 13 without and 5 with symptoms. We evaluated survival after nipple-sparing mastectomy versus non-nipple-sparing mastectomy in a population-based cancer registry.We conducted an observational study using the California Cancer Registry, considering all stage 0-III breast cancers diagnosed in California from 1988 to 2013. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. All statistical tests were 2-sided.Among 2,293 patients, 1,451 had HR-positive/HER2-negative disease and 842 had TNBC. In this review, we summarize the current understanding of pathogenic germline gene mutations associated with TNBC and the early detection and prevention strategies for women at risk of developing this high-risk breast cancer subtype. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the In a simulation study, we demonstrate that the proposed sequential regression multiple imputation modifications result in reduced bias in the final analysis compared to standard sequential regression multiple imputation, with an approximation strategy involving inclusion of an offset in the imputation model performing the best overall. All P values are two-sided.We did not observe an age-related black-white crossover in incidence for any molecular subtype of breast cancer. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER+/ERBB2-, 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+/ERBB2+, 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER-/ERBB2+, 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER-/ERBB2-, 48% (model range, 38%-57%) vs 52% (model range, 44%-62%).In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype. We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity.We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)-together referred to as hormone receptor (HR)-and human epidermal growth factor receptor 2 (HER2). Keren, L., Bosse, M., Marquez, D., Angoshtari, R., Jain, S., Varma, S., Yang, S., Kurian, A., Van Valen, D., West, R., Bendall, S. C., Angelo, M. From the Past to the Present: Insurer Coverage Frameworks for Next-Generation Tumor Sequencing. pharmacokinetics of atezolizumab (MPDL3280A) administered with nab-paclitaxel compared with Cause-specific competing risk regression was applied to evaluate an association between BM risk and the mode of PLC detection-i.e., LDCT screen-detected versus non-LDCT screen-detected. Lnning, P. E., Nikolaienko, O., Pan, K., Kurian, A. W., Eikesdal, H. P., Pettinger, M., Anderson, G. L., Prentice, R. L., Chlebowski, R. T., Knappskog, S. Incident comorbidities after tamoxifen or aromatase inhibitor therapy in a racially and ethnically diverse cohort of women with breast cancer. Home-grown Born in the late '60s, Kurian grew up in a small town called Pampady in Kerala's Kottayam district. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results. The stomach and resected lymph nodes were evaluated pathologically.Six patients were identified as CDH1 carriers from a single family. We surveyed them, and then invited eligible respondents to an online platform hosted by a navigator that offered cancer genetic risk education and germline genetic testing to untested relatives. View details for Web of Science ID 000318174800096. 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. Kwong, A., Ng, E. K., Law, F. B., Wong, H. N., Wa, A., Wong, C. L., Kurian, A. W., West, D. W., Ford, J. M., Ma, E. S. Genetic Polymorphisms as Predictors of Breast Cancer Risk, Identification of BRCA1/2 Founder Mutations in Southern Chinese Breast Cancer Patients Using Gene Sequencing and High Resolution DNA Melting Analysis. Next-generation sequencing promises major advancements in precision medicine but faces considerable challenges with insurance coverage. Lin, G. A., Trosman, J. R., Douglas, M. P., Weldon, C. B., Scheuner, M. T., Kurian, A., Phillips, K. A. Kurian, A. W., Mills, M. A., Jaffee, M., Sigal, B. M., Chun, N. M., Kingham, K. E., Collins, L. C., Nowels, K. W., Plevritis, S. K., Garber, J. E., Ford, J. M., Hartman, A. R. Histologic types of epithelial ovarian cancer: have they different risk factors? A cox proportional hazards model was used to evaluate survival while controlling for clinical and demographic factors.The best survival pattern was observed among women with HR+/HER2- subtype (survival rate of 92.5% at four years), followed by HR+/HER2+ (90.3%), HR-/HER2+ (82.7%), and finally worst survival for triple-negative subtype (77.0%). Hispanic respondents were less likely to have told a healthcare provider about their results than NHW (29% vs. 68%, p < .0001). Participants carried an average of 2.1 variants of uncertain significance among 42 genes.Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp. B., Lee, R., Chan, S., Donlon, S. S., Ridge, Y., Panabaker, K., West, D. W., Whittemore, A. S., Ford, J. M. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. For patients carrying a VUS, clinical documentation was assessed for evidence of provider awareness of the conflict.50/975 (5.1%) patients with non-negative results carried a variant with a clinically significant conflict, 19 with a P/LP variant reported in APC or MUTYH, and 31 with a VUS reported in CDKN2A, CHEK2, MLH1, MSH2, MUTYH, RAD51C, or TP53. Prophylactic mastectomy (PM) is often considered, but variably chosen by women at high inherited risk of breast cancer; few data exist on patient tolerance of intensive breast screening as an alternative to PM. The impact of significant others on breast cancer patients treatment decision making. Allison W. Kurian, M.D., M.Sc. HER2 mutated cancer responds to treatment with neratinib. View details for DOI 10.1093/jnci/djab151. Compared with women with the lowest level of recent recreational physical activity, those with the highest level had a marginally decreased risk of all-cause mortality (hazard ratio = 0.88, 95% confidence interval: 0.76, 1.01) and a statistically significant decreased risk of mortality from causes other than breast cancer (hazard ratio = 0.63, 95% confidence interval: 0.49, 0.80), and particularly from cardiovascular disease. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. These results may reassure newly diagnosed patients and longer follow-up is ongoing. Lincoln, S. E., Kobayashi, Y., Anderson, M. J., Yang, S., Desmond, A. J., Mills, M. A., Nilsen, G. B., Jacobs, K. B., Monzon, F. A., Kurian, A. W., Ford, J. M., Ellisen, L. W. Precision Medicine in Breast Cancer Care: An Early Glimpse of Impact. 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. View details for PubMedCentralID PMC7446363, View details for DOI 10.1158/1538-7445.AM2020-2033. A., Gaudet, M. M., Giles, G. G., Glendon, G., Goldberg, M. S., Goldgar, D. E., Gonzlez-Neira, A., Grip, M., Gunel, P., Hahnen, E., Haiman, C. A., Hkansson, N., Hall, P., Hamann, U., Han, S., Harkness, E. F., Hart, S. N., He, W., Heemskerk-Gerritsen, B. In the multivariable model, when clinical and SES variables were controlled for, racial differences in test uptake were no longer observed. Charges, claims, and reimbursements are related to cost but are nontransparent and proprietary. Thomas Kurian, chief executive officer of cloud services at Google LLC, speaks during the Google Cloud Next '19 event in San Francisco, California, U.S., on Tuesday, April 9, 2019. postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study Thomas Kurian launched Anthos, a Google Cloud platform for companies to put and manage their data in different clouds. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGF1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. Assuming one third of metastatic cancers were diagnosed at stage III, one third diagnosed at stage II, and one third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24% of all cancer-related deaths, corresponding to a reduction in all-cause mortality comparable in magnitude to eliminating deaths due to cerebrovascular disease.Detection of multiple cancer types earlier than stage IV could reduce at least 15% of cancer-related deaths within 5 years, affecting not only cancer-specific but all-cause mortality.Detecting cancer before stage IV, including modest shifts to stage III, could offer substantial population benefit. Telli, M. L., Kurian, A. W., Jensen, K. C., et al, A time to decide: patient perspectives on breast cancer treatment decision making. 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. Most women received first-recorded therapy with endocrine (67%) versus chemotherapy, underwent more computed tomography (CT) (76%) than positron emission tomography-CT, and were monitored using tumor markers (58%). [19] He was also the fifth highest-paid tech executive in 2010. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System to examine the neighborhood environment, body mass index, and mortality after breast cancer. Gallagher, S. n., Hughes, E. n., Wagner, S. n., Tshiaba, P. n., Rosenthal, E. n., Roa, B. Lowry, K. P., Geuzinge, H., Stout, N. K., Alagoz, O., Hampton, J. M., Kerlikowske, K., Miglioretti, D. L., Schecter, C., Sprague, B. L., Trentham-Dietz, A., Tosteson, A. An adoption timeline was constructed.Sixty-nine payers had a sequencing policy. [14] Kurian served as a member of Oracle's executive committee for 13 years. Our hypothesis is that by combining molecular signatures with clinicopathologic features, we can elucidate the biology of breast cancer progression, and risk-stratify patients with DCIS.Targeted exon sequencing with a custom panel of 223 genes/regions was performed for 125 DCIS cases. We developed an online tool to guide decisions about cancer risk reduction (available at: http://brcatool.stanford.edu ), and recruited patients and clinicians to test its feasibility. The incidence of LS in this cohort was evaluated.MMR-D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%-8.3%) primary ovarian-related cancers. Our findings inform 3 areas of the PMI: addressing insurance coverage to secure access to future PMI discoveries; incorporating payers' evidentiary requirements into PMI's research agenda; and leveraging payers' recommendations and experience to keep patients informed and involved. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain.Further study of the impact of prophylactic oophorectomy on breast cancer risk in BRCA1/2 mutation carriers is warranted. View details for DOI 10.1038/s41598-020-65665-y. Kurian, A. W., Hughes, E., Bernhisel, R., Larson, K., Caswell-Jin, J., Shadyab, A. H., Ochs-Balcom, H., Pan, K., Qi, L., Reding, K., Hartman, A., Lancaster, J. M., Tang, J. Y., Stefanick, M. L. Radiomics features to identify distinct subtypes of triple-negative breast cancers. The Phase I Compared with being adherent to none (n=55 cancers), being adherent to any ACS recommendation (n=563 cancers) was associated with a 27% lower breast cancer risk (HR=0.73, 95% CI: 0.55-0.97). Results of ongoing trials will be essential to confirm the quality of this approach to breast cancer care. We examined the performances of the IBIS and BOADICEA risk models when using alternative thresholds by comparing predictions based on 5-year risk with those based on lifetime risk from birth and remaining lifetime risk. For more information, please contact Naheed Mangi, 650-723-0658. Triple-negative breast cancer is associated with a young age at diagnosis and both African and Ashkenazi Jewish ancestry, the latter due to three common founder mutations in the highly penetrant cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2). A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study). 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? Oncologists explained 17% of the variation in RS testing but little of the variation in chemotherapy receipt (3%) controlling for clinical factors. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown.To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort.Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. Kurian, A. W., Munoz, D. F., Rust, P., Schackmann, E. A., Smith, M., Clarke, L., Mills, M. A., Plevritis, S. K. Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry. Non-melanoma skin cancer (NMSC), the most prevalent cancer in the US,(1) has been associated with increased risk of non-cutaneous malignancies, including breast cancer, lung cancer, and lymphoma. However, epidemiologic studies on circulating melatonin are limited because melatonin is secreted at night, yet most epidemiologic studies collect blood during the day when melatonin levels are very low, and assays are lacking that are ultrasensitive to detect low levels of melatonin reliably.To assess the performance of a refined radioimmunoassay in measuring morning melatonin among women.We used morning serum samples from 47 postmenopausal women ages 48-80 years without a history of breast cancer who participated in the San Francisco Bay Area Breast Cancer Study, including 19 women who had duplicate measurements. Better risk communication by clinicians may translate to better risk comprehension among patients and to improvements in QoL. Multivariable analysis was performed to identify predictors of RS and chemotherapy use.In all, 10,125 patients with breast cancer were diagnosed in the University or Community systems from 2005 to 2011; 2,418 (23.9%) met RS guidelines criteria, of whom 15.6% received RS. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia. Model input parameters were derived from meta-analyses, clinical trials, and large observational data. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy.For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. 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