placebo in combination with nab-paclitaxel in participants with locally advanced or View details for DOI 10.1200/JOP.19.00221, The detection rate of breast ductal carcinoma in situ (DCIS) has increased significantly, raising the concern that DCIS is overdiagnosed and overtreated. Daly, M. B., Axilbund, J. E., Buys, S., Crawford, B., Farrell, C. D., Friedman, S., Garber, J. E., Goorha, S., Gruber, S. B., Hampel, H., Kaklamani, V., Kohlmann, W., Kurian, A., Litton, J., Marcom, P. K., Nussbaum, R., Offit, K., Pal, T., Pasche, B., Pilarski, R., Reiser, G., Shannon, K. M., Smith, J. R., Swisher, E., Weitzel, J. N. Increasing Mastectomy Rates for Early-Stage Breast Cancer? However, each patient (6 of 6, 100%) was found to have multiple foci of T1 invasive diffuse gastric adenocarcinoma (pure signet-ring cell type). Risk stratification with a 20% risk threshold was compared between CRS and Tyrer-Cuzick in an independent clinical cohort (N = 32,576).Simulation studies confirmed that the Fixed-Stratified method produced accurate risk estimation across patients with different family history. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. We examined patient reports of cancer worry by test type and results in 1,063 women who linked to a genetic test and reported undergoing testing.More than half of the sample (n = 640; 60.2%) received BRCA1/2-only testing versus 423 patients (39.8%) who had a multigene panel. Zeidman, A., Benedict, C., Zion, S. R., Fisher, S., Tolby, L., Kurian, A. W., Berek, J. S., Woldeamanuel, Y. W., Schapira, L., Palesh, O. We examined whether accounting for racial/ethnic differences in the prevalence of clinical, patient, and lifestyle and contextual factors that are associated with breast cancer-specific mortality can explain this disparity.The California Breast Cancer Survivorship Consortium combined interview data from six California-based breast cancer studies with cancer registry data to create a large racially diverse cohort of women with primary invasive breast cancer. B., Itakura, H. Contributions of screening, early-stage treatment, and metastatic treatment to breast cancer mortality reduction by molecular subtype in US women, 2000-2017. Imputing HLA genotypes from existing single-nucleotide polymorphism datasets is low-cost and efficient. A., Kurian, A. W., Das, A. K., Desai, M. Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. Multivariable models and matched case-control analyses yielded similar results.Among nearly 100,000 clinically tested women, 7% carried a pathogenic mutation in one or more cancer-associated genes. Participants were queried about communication of their results, as part of a prospective study of multi-gene panel genetic testing. Results were similar for breast cancer-specific survival, except that African Americans and non-Hispanic Whites living in high-SES neighborhoods had similar survival.Strategies to address the underlying factors that may influence treatment intensity and adherence, such as comorbidities and logistical barriers, should be targeted at low-SES non-Hispanic White and all African American patients. Applying multivariate analyses, we show that each additional total or unique monthly antimicrobial prescription is associated with inferior overall and breast cancer-specific survival. An optimized PRS was validated in 2 independent cohorts (n = 13,174; n = 141,160).Within the training cohort (n = 24,259), 4,291 women (18%) had a personal history of breast cancer and 8,725 women (36%) reported breast cancer in a first-degree relative. 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). 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. Compared to NL White women with high-education/high-nSES, higher all-cause mortality was observed among NL White women with high-education/low-nSES [hazard ratio (HR) (95% confidence interval) 1.24 (1.08-1.43)], and African American women with low-nSES, regardless of education [high education HR 1.24 (1.03-1.49); low-education HR 1.19 (0.99-1.44)]. Results of ongoing trials will be essential to confirm the quality of this approach to breast cancer care. Telli, M. L., Jensen, K. C., Kurian, A. W., Vinayak, S., Lipson, J. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS.We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Weight is more informative than BMI for predicting breast cancer risk, consistent with non-adipose as well as adipose tissue being etiologically relevant. Mitani, A. Our data come from a one-time evaluation of cancer survivors at a single clinic and provide a foundation for future longitudinal studies and RCTs on the relationship between mindsets and psychosocial outcomes in cancer survivors. Along with educational level and use of internet support groups, uncertain results on genomic testing predicted second opinion use. Kurian, A. W., Hartman, A. R., Mills, M. A., Ford, J. M., Daniel, B. L., Plevritis, S. K. Ductal lavage of fluid-yielding and non-fluid-yielding ducts in BRCA1 and BRCA2 mutation carriers and other women at high inherited breast cancer risk. Research suggests that adherence to the 2012 ACS Guideline might lower breast cancer risk, but there is limited evidence that this applies to women at increased familial and genetic risk of breast cancer.Using the Breast Cancer Family Registry (BCFR), a cohort enriched for increased familial and genetic risk of breast cancer, we examined adherence to three 2020 ACS Guideline recommendations (weight management (body mass index), physical activity, and alcohol consumption) with breast cancer risk in 9615 women. Multivariable models evaluated correlates of a strong desire for genetic testing, unmet need for discussion with a health care professional, and receipt of testing.Among 1,536 patients who completed the survey, 35% expressed strong desire for genetic testing, 28% reported discussing testing with a health care professional, and 19% reported test receipt. We considered the following comorbidities: cerebrovascular accidents, congestive heart failure, dementia, depression/anxiety, diabetes mellitus, hyperlipidemia, myocardial infarction, non-alcoholic steatohepatitis, osteoporosis/fracture, peripheral vascular disease, and venous thromboembolism. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. - Cohort 2) Subjects who have received > 2 prior chemotherapy regimens for metastatic Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR(+)/HER2(-) breast cancers after age 35 years (all P < .05). We report lavage of fluid-yielding and non-fluid-yielding ducts in women at high inherited breast cancer risk.A pilot breast cancer screening study including ductal lavage was conducted in 75 women at high inherited risk, 56 (74.7%) of whom had BRCA1/2 mutations. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. These findings warrant intensive surveillance for second breast cancers in women with HR-negative tumors. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit. Furthermore, in the 57 carriers and subsequently tested relatives with two years of follow-up, a total of three cancers (one in a proband and two in relatives) were detected through interventions recommended on the basis of the pathogenic variant. Schackmann, E. A., Vinayak, S., Kurian, A. W., et al. Clinical guidelines often use predicted lifetime risk from birth to define criteria for making decisions regarding breast cancer screening rather than thresholds based on absolute 5-year risk from current age.We used the Prospective Family Cohort Study of 14,657 women without breast cancer at baseline in which, during a median follow-up of 10years, 482 women were diagnosed with invasive breast cancer. Relationships between sociodemographic and clinical factors and GCC receipt differed by subtype. 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. Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Levonian, P., Hong, C., Mills, M., Ma, C., Lancaster, J. M., Brown, K., Kidd, J., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. Oncotype DX DCIS use and clinical utility: A SEER population-based study. For more information, please contact Annabel Castaneda, 650-498-7977. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Kim, S. M., Hatami, F., Harris, J. S., Kurian, A. W., Ford, J., King, D., Scalari, G., Giovannini, M., Hoyler, N., Faist, J., Harris, G. Comparative Analysis of Bio-Medical Imaging at 3.7 Terahertz with a High Power Quantum Cascade Laser, Kim, S. M., Hatami, F., Gu, A., Kurian, A. W., et al, A clinic-based study of BRCA1/2 mutation epidemiology in Asians, Kurian, A. W., Chun, N. M., Millls, M. A., et al, Opinions of women with high inherited breast cancer risk about prophylactic mastectomy: an initial evaluation from a screening trial including magnetic resonance imaging and ductal lavage. A., Mebirouk, N., Menon, U., Miller, A., Milne, R. L., Minlikeeva, A., Modugno, F., Montagna, M., Moysich, K. B., Munro, E., Nathanson, K. L., Neuhausen, S. L., Nevanlinna, H., Yie, J. N., Nielsen, H. R., Nielsen, F. C., Nikitina-Zake, L., Odunsi, K., Offit, K., Olah, E., Olbrecht, S., Olopade, O. I., Olson, S. H., Olsson, H., Osorio, A., Papi, L., Park, S. K., Parsons, M. T., Pathak, H., Pedersen, I. S., Peixoto, A., Pejovic, T., Perez-Segura, P., Permuth, J. hormone receptor-positive breast cancer. Gallagher, S., Hughes, E., Wagner, S., Tshiaba, P., Rosenthal, E., Roa, B. These results may reassure newly diagnosed patients and longer follow-up is ongoing. 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. Twin studies suggest that MD phenotypes are highly heritable. Cause-specific Cox proportional hazards models were fit to time-to-new-diagnosis for each comorbidity, accounting for death as a competing risk. Participants included 2023 patients with cancer who received germline testing and previously underwent tumor DNA sequencing. However, access to genetic counseling is a barrier and must be addressed to ensure equity in testing. Feb 27 Google Public Sector is working with @ALPLM to help bring history to life by creating engaging experiences for visitors with AI, extended reality & AR technologies. Participants were followed for on average 11.45 years and there were 416 incident breast cancers. 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. Women's health clinicians are poised to evaluate risk, promote breast cancer risk reduction, and manage overall health. Treatment decisions and employment of breast cancer patients: Results of a population-based survey. Telli, M. L., Chang, E. T., Kurian, A. W., Keegan, T. H., McClure, L. A., Lichtensztajn, D., Ford, J. M., Gomez, S. L. Hereditary cancer: counseling women at risk. View details for DOI 10.1038/s41416-021-01432-8. 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. Research on the communication of genetic test results has focused predominately on non-Hispanic White (NHW) mutation-positive families with high-risk hereditary cancer conditions. health literacy, numeracy, and anxiety/worry) on physician communication outcomes was evaluated in multivariable regression models (analytic sample for substudy=1295).About 33% of women reported that doctors discussed risk of recurrence as "quite a bit" or "a lot," while 14% said "not at all." These findings highlight a need for focused efforts to improve adherence to surveillance and prevent delays in detection of breast cancer recurrence and second cancers. Associations between CPM receipt and surgeon recommendations were also evaluated. View details for PubMedID 35723570, View details for DOI 10.1093/jncics/pkac045. Who is Thomas Kurian wife? [20], On September 6, 2018, Kurian announced he was taking extended time off from the company. Logistic and linear regression models were used to evaluate for association of clinical trial engagement and patient portal message rates with primary language group.Patients with LEP had significantly lower rates of clinical trial engagement compared with their English-speaking counterparts (adjusted odds ratio [OR], 0.29; 95% CI, 0.16 to 0.51). Nearly half (46%) met criteria for aggressive disease, which were associated with receiving chemotherapy first, monitoring primarily with CT, and more frequent imaging. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35-0.69) and BRCA2 PVs (HR=0.60, 95% CI=0.41-0.89), and equivalent with PVs in other genes (HR=0.65, 95% CI=0.37-1.13), versus non-carriers. 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. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Kurian, A. W., Abrahamse, P., Ward, K. C., Hamilton, A. S., Deapen, D., Berek, J. S., Hoang, L., Yussuf, A., Dolinsky, J., Brown, K., Slavin, T., Hofer, T. P., Katz, S. J. Clinicians should collect toxicity data routinely and offer early intervention. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for BRCA1, 27% for BRCA2, and 13% for CHEK2 PV carriers with breast cancer and 35% for PALB2 PV carriers with ER-negative breast cancer. The 21-gene recurrence score (RS) identifies patients with breast cancer who derive little benefit from chemotherapy; it may reduce unwarranted variability in the use of chemotherapy. Most respondents were eligible for the trial offer (113 of 125; 90.4%). His first executive role was as Vice President of Oracle's e-Business division. The two models showed similar discrimination in each racial/ethnic group, discriminating least well in Hispanics. Clinician discussions about recurrence risk should address uncertainty and relevance of family and personal history. 7 Richest Indian CEOs in the world - 1. For more information, please contact Ashley Powell, (650) 724 - 3308. Wang, A., Wakelee, H. A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Stefanick, M. L. Equivalent survival after nipple-sparing compared to non-nipple-sparing mastectomy: data from California, 1988-2013. 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. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results. My research employs methods from the population sciences, in collaboration the Surveillance, Epidemiology and End Results (SEER) Program. Yadav, S., Hu, C., Nathanson, K. L., Weitzel, J. N., Goldgar, D. E., Kraft, P., Gnanaolivu, R. D., Na, J., Huang, H., Boddicker, N. J., Larson, N., Gao, C., Yao, S., Weinberg, C., Vachon, C. M., Trentham-Dietz, A., Taylor, J. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works efficacy of the combination will also be collected. After adjusting for covariates, RPA (any vs none) was associated with lower all-cause mortality of 16.1% (95% confidence interval [CI] = 2.4% to 27.9%) overall, 11.8% (95% CI = -3.6% to 24.9%) in women without BRCA1/2 PVs, and 47.5% (95% CI = 17.4% to 66.6%) in women with BRCA1/2 PVs (RPA*BRCA1/2 multiplicative interaction P = .005; relative excess risk due to interaction = 0.87, 95% CI = 0.01 to 1.74). For more information, please contact Pei-Jen Chang, (650) 725 - 0866. (7) We sought to replicate these prospective findings in the large WHI cohort, for which important potential confounders, e.g. Lowry, K. P., Geuzinge, H. A., Stout, N. K., Alagoz, O., Hampton, J., Kerlikowske, K., de Koning, H. J., Miglioretti, D. L., van Ravesteyn, N. T., Schechter, C., Sprague, B. L., Tosteson, A. N., Trentham-Dietz, A., Weaver, D., Yaffe, M. J., Yeh, J. M., Couch, F. J., Hu, C., Kraft, P., Polley, E. C., Mandelblatt, J. S., Kurian, A. W., Robson, M. E. Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019. Understanding of cancer outcomes is limited by data fragmentation. Jayasekera, J., Sparano, J. Use of the 21-gene recurrence score (RS) did not change among node-negative/micrometastasis patients, and increasing RS use in node-positive patients accounted for one-third of the chemotherapy decline. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate).Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. 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. Goodness-of-fit analysis compared expected with observed relative risks by quantiles of the MA-PRS distribution.In independent validation, the MA-PRS was significantly associated with BC risk in the full cohort (odds ratio, 1.43; 95% CI, 1.40 to 1.46; P = 8.6 10-308) and within each major ancestry. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2.Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies. The authors assessed the frequency and severity of toxicities; correlated toxicity severity with unscheduled health care use (clinic visits, emergency department visits/hospitalizations) and physical health; and examined patient, tumor, and treatment factors associated with reporting increased toxicity severity.The overall survey response rate was 71%. Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States. We compared the ability of each NLP model to identify the presence, timing, and site of recurrence, when compared against manual chart review and International Classification of Diseases coding.A total of 1,273 patients were included in the development and validation of the two models. Chemotherapy details were extracted from SEER text fields completed by registrars. In this study, we developed a weak-supervision framework for breast cancer recurrence prediction in which we trained a deep learning model on a large sample of free-text clinic notes by utilizing a combination of manually curated labels and NLP-generated non-perfect recurrence labels. View details for PubMedID 25847940, View details for DOI 10.1200/JCO.2014.58.5885. Among ovarian cancer patients in North America, BRCA1/2 mutations are present in 13-15%. Oncologists explained 17% of the variation in RS testing but little of the variation in chemotherapy receipt (3%) controlling for clinical factors. Jagsi, R., Abrahamse, P., Lee, K., Wallner, L. P., Janz, N. K., Hamilton, A. S., Ward, K. C., Morrow, M., Kurian, A. W., Friese, C., Hawley, S. T., Katz, S. J. The most influential variables were related to disease characteristics, neighborhood socioeconomic status, and smoking status at diagnosis. 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. pbfhkH. BRCA1/2 mutation prediction models (BRCAPRO, Myriad II, Couch, Shattuck-Eidens, BOADICEA) are well established in western cohorts to estimate the probability of BRCA1/2 mutations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer. A Clinical Trial of PM01183 in Metastatic Breast Cancer to assess the antitumor activity of There were few differences between states. If results are promising, they may justify a randomized trial of statins for breast cancer chemoprevention, with a focus on HR-negative disease. Hughes, E. n., Tshiaba, P. n., Gallagher, S. n., Wagner, S. n., Judkins, T. n., Roa, B. n., Rosenthal, E. n., Domchek, S. n., Garber, J. n., Lancaster, J. n., Weitzel, J. n., Kurian, A. W., Lanchbury, J. S., Gutin, A. n., Robson, M. n. Abstract 2033: Reducing cancer caregiver burden: A user-centered design approach for an mHealth app. This is a 3 arm Phase 3 study to evaluate the safety and efficacy of the addition of For women whose first breast tumors were HR negative, the risk of a contralateral primary tumor was statistically significantly higher than that for women whose first tumors were HR positive (SIR = 3.57, 95% CI = 3.38 to 3.78, AR = 18 per 10 000 PY), and it was associated with a much greater likelihood of an HR-negative second tumor (SIR for HR-positive second tumors = 1.94, 95% CI = 1.77 to 2.13, AR = 20 per 10 000 PY; SIR for HR-negative second tumors = 9.81, 95% CI = 9.00 to 10.7, AR = 24 per 10 000 PY). A larger screening trial is needed to determine which subgroups of high-risk women will benefit and whether the identification of malignant and high-risk lesions at an early stage will impact breast carcinoma incidence and mortality.