Use of Gene Expression Profiling and Chemotherapy in Early-Stage Breast Cancer: A Study of Linked Electronic Medical Records, Cancer Registry Data, and Genomic Data Across Two Health Care Systems

Afghahi, Anosheh; Mathur, Maya B.; Thompson, Caroline A.; Mitani, Aya A.; Rigdon, Joseph; Desai, Manisha; Yu, Peter Paul; Bruin, Monique A. de; Seto, Tina; Olson, Cliff; Kenkare, Pragati; Gomez, Scarlett Lin; Das, Amar K.; Luft, Harold S.; Sledge, George W.; Sing, Amy P.; Kurian, Allison W.

doi:10.1200/jop.2015.009803

Cited by 13 publications

(17 citation statements)

References 26 publications

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“…We hypothesized that antihypertensive agents that inhibit the RAAS system are more efficacious in modulating VEGFi-mediated blood pressure elevation. Electronic health records (EHRs) have been used in several recent precision medicine projects in both oncology and hypertension ( 13 – 16 ). To test this hypothesis, we used the EHR to investigate the effect of pre-treatment RAASi therapy on change in mean systolic and mean diastolic blood pressure in patients treated with VEGFis.…”

mentioning

confidence: 99%

Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition

Bottinor

Shuey

Manouchehri

et al. 2019

JACC: CardioOncology

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OBJECTIVES This study postulated that antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibition may mitigate vascular endothelial growth factor inhibitor (VEGFi)–mediated increases in blood pressure more effectively than other antihypertensive medications in patients receiving VEGFi therapy. BACKGROUND VEGFi therapy is commonly used in the treatment of cancer. One common side effect of VEGFi therapy is elevated blood pressure. Evidence suggests that the RAAS may be involved in VEGFi-mediated increases in blood pressure. METHODS This retrospective cohort analysis was performed using a de-identified version of the electronic health record at Vanderbilt University Medical Center in Nashville, Tennessee. Subjects with cancer who were exposed to VEGFi therapy were identified, and blood pressure and medication data were extracted. Changes in mean systolic and diastolic blood pressure in response to VEGFi therapy in patients receiving RAAS inhibitor (RAASi) therapy before VEGFi initiation were compared with changes in mean systolic and diastolic blood pressure in patients not receiving RAASi therapy before VEGFi initiation. RESULTS Mean systolic and diastolic blood pressure rose in both groups after VEGFi use; however, patients who had RAASi therapy before VEGFi initiation had a significantly lower increase in systolic blood pressure as compared with patients with no RAASi therapy (2.46 mm Hg [95% confidence interval: 0.7 to 4.2] compared with 4.56 mm Hg [95% confidence interval: 3.5 to 5.6], respectively; p = 0.034). CONCLUSIONS In a real-world clinical population, RAASi therapy before VEGFi initiation may ameliorate VEGFi-mediated increases in blood pressure. Randomized clinical trials are needed to further our understanding of the role of RAASi therapy in VEGFi-mediated increases in blood pressure. (J Am Coll Cardiol CardioOnc 2019;1:14–23)

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mentioning

confidence: 99%

Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition

Bottinor

Shuey

Manouchehri

et al. 2019

JACC: CardioOncology

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“…Genotyping at particular loci has been used with the number and duration of in-patient events in schizophrenia [ 24 ]. Gene expression profiling has been used in conjunction with electronic health records (EHRs) to compare breast cancer treatments and predict chemotherapy efficacy and outcomes across health care systems [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Toward a Risk-Utility Data Governance Framework for Research Using Genomic and Phenotypic Data in Safe Havens: Multifaceted Review

Jones¹,

Daniels²,

Heys³

et al. 2020

J Med Internet Res

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Background Research using genomic data opens up new insights into health and disease. Being able to use the data in association with health and administrative record data held in safe havens can multiply the benefits. However, there is much discussion about the use of genomic data with perceptions of particular challenges in doing so safely and effectively. Objective This study aimed to work toward a risk-utility data governance framework for research using genomic and phenotypic data in an anonymized form for research in safe havens. Methods We carried out a multifaceted review drawing upon data governance arrangements in published research, case studies of organizations working with genomic and phenotypic data, public views and expectations, and example studies using genomic and phenotypic data in combination. The findings were contextualized against a backdrop of legislative and regulatory requirements and used to create recommendations. Results We proposed recommendations toward a risk-utility model with a flexible suite of controls to safeguard privacy and retain data utility for research. These were presented as overarching principles aligned to the core elements in the data sharing framework produced by the Global Alliance for Genomics and Health and as practical control measures distilled from published literature and case studies of operational safe havens to be applied as required at a project-specific level. Conclusions The recommendations presented can be used to contribute toward a proportionate data governance framework to promote the safe, socially acceptable use of genomic and phenotypic data in safe havens. They do not purport to eradicate risk but propose case-by-case assessment with transparency and accountability. If the risks are adequately understood and mitigated, there should be no reason that linked genomic and phenotypic data should not be used in an anonymized form for research in safe havens.

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“…Thus, results may vary in other practice settings and organizational structures. However, increasing numbers of physicians are practicing in accountable care organizations or other integrated systems, and the observed rate of test use in eligible patients (39%) was similar to or higher than that in most other settings [3,6,8,25–27], and has increased from earlier reported rates in this setting [5]. On balance, the variability we observed in testing rates among practice groups suggests that financial access alone will not ensure consistent use of cancer genomic tests.…”

Section: Discussionmentioning

confidence: 99%

Oncologist and organizational factors associated with variation in breast cancer multigene testing

Lieu

Ray

Prausnitz

et al. 2017

Breast Cancer Res Treat

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Purpose Multigene testing for breast cancer recurrence risk became available in 2007, yet many eligible patients remain untested. This study evaluated variation in testing rates, and oncologist and organizational factors associated with variation, in a setting without financial influences on testing. Methods We conducted a retrospective cohort study using electronic data and oncologist surveys within Kaiser Permanente Northern California, a large integrated health care system. Analyses included all 2,974 test-eligible patients from 2013–15, 113 oncologists, and 15 practice groups. Receipt of multigene testing was evaluated with generalized linear mixed models. Results Overall, 39% of eligible patients had multigene testing, but rates varied widely among practice groups, ranging from 24 to 48% after case-mix adjustment. This 24% difference among practices was greater than the variation associated with most patient characteristics, including comorbidities and race/ethnicity, and similar to that associated with tumor size. Practice group and oncologist factors were statistically significant contributors to the variation in testing after adjusting for patient factors. Patients were more likely to be tested if they had a female oncologist (aOR 1.60, 95% CI 1.21 – 2.12) or were in a practice whose chief had a high testing rate (aOR 1.20, 95% CI 1.12 – 1.29 per 10% increase in the percent tested). Conclusions Oncologist and leadership practices play a key role in the variation in genomic test use for cancer recurrence risk even in a healthcare system without financial barriers to testing, and could be a leverage point for implementing desired practice changes for new genomic advances.

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Use of Gene Expression Profiling and Chemotherapy in Early-Stage Breast Cancer: A Study of Linked Electronic Medical Records, Cancer Registry Data, and Genomic Data Across Two Health Care Systems

Cited by 13 publications

References 26 publications

Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition

Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition

Toward a Risk-Utility Data Governance Framework for Research Using Genomic and Phenotypic Data in Safe Havens: Multifaceted Review

Oncologist and organizational factors associated with variation in breast cancer multigene testing

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