Publications by authors named "Mirar Bristol Demeter"

6 Publications

  • Page 1 of 1

Age at diagnosis may trump family history in driving BRCA testing in a population of breast cancer patients.

Cancer Epidemiol Biomarkers Prev 2013 Oct 5;22(10):1778-85. Epub 2013 Aug 5.

Authors' Affiliations: Cancer Institute of New Jersey, New Brunswick, New Jersey; and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Background: Standard BRCA genetic testing criteria include young age of diagnosis, family history, and Jewish ancestry. The purpose of this study was to assess the effect of these criteria on BRCA test utilization in breast cancer patients.

Methods: Breast cancer patients aged 18 to 64 years living in Pennsylvania in 2007 completed a survey on family history of breast and ovarian cancer and BRCA testing (N = 2,213). Multivariate logistic regression was used to estimate odds of BRCA testing by patient characteristics, and predicted probabilities of testing were calculated for several clinical scenarios.

Results: Young age at diagnosis (<50 years) was strongly associated with BRCA testing, with women diagnosed before age 50 years having nearly five times the odds of receiving BRCA testing compared to women diagnosed at age 50 or older (OR = 4.81; 95% CI, 3.85-6.00; P < 0.001). Despite a similar BRCA mutation prevalence estimate (8-10%), a young Jewish patient <50 years with no family history had markedly higher predicted probability of testing (63%) compared with an older, non-Jewish breast cancer patient with more than one first-degree relative (43%).

Conclusion: Age at diagnosis, Jewish ancestry, and both maternal and paternal family history are strongly predictive of BRCA testing. However, among women diagnosed at age 50 or older, family history may be an underused criterion that may benefit from targeted intervention.

Impact: Robust methods specific to ascertaining detailed family history, such as through electronic medical records, are needed to accurately identify patients for BRCA testing.
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October 2013

Incremental impact of breast cancer SNP panel on risk classification in a screening population of white and African American women.

Breast Cancer Res Treat 2013 Apr 10;138(3):889-98. Epub 2013 Mar 10.

Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, Room 1009, Philadelphia, PA 19104, USA.

Breast cancer risk prediction remains imperfect, particularly among non-white populations. This study examines the impact of including single-nucleotide polymorphism (SNP) alleles in risk prediction for white and African American women undergoing screening mammogram. Using a prospective cohort study, standard risk information and buccal swabs were collected at the time of screening mammography. A 12 SNP panel was performed by deCODE genetics. Five-year and lifetime risks incorporating SNPs were calculated by multiplying estimated Breast Cancer Risk Assessment Tool (BCRAT) risk by the total genetic risk ratio. Concordance between the BCRAT and the combined model (BCRAT + SNPs) in identifying high-risk women was measured using the kappa statistic. SNP data were available for 810 women (39 % African American, 55 % white). The mean BCRAT 5-year risk was 1.71 % for whites and 1.18 % for African Americans. Mean genetic risk ratios were 1.09 in whites and 1.29 in African Americans. Among whites, three SNPs had higher frequencies, and among African Americans, seven SNPs had higher and four had lower high-risk allele frequencies than previously reported. Agreement between the BCRAT and the combined model was relatively low for identifying high-risk women (5-year κ = 0.54, lifetime κ = 0.36). Addition of SNPs had the greatest effect among African Americans, with 12.4 % identified as having high-5-year risk by BCRAT, but 33 % by the combined model. A greater proportion of African Americans were reclassified as having high-5-year risk than whites using the combined model (21 vs. 10 %). The addition of SNPs to the BCRAT reclassifies the high-risk status of some women undergoing screening mammography, particularly African Americans. Further research is needed to determine the clinical validity and utility of the SNP panel for use in breast cancer risk prediction, particularly among African Americans for whom these risk alleles have generally not been validated.
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April 2013

Cost effectiveness of personalized therapy for first-line treatment of stage IV and recurrent incurable adenocarcinoma of the lung.

J Oncol Pract 2012 Sep 19;8(5):267-74. Epub 2012 Jun 19.

University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Purpose: Patients with epidermal growth factor receptor (EGFR) mutation-positive stage IV adenocarcinoma have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the cost effectiveness of personalized first-line therapy using EGFR mutation testing is unknown.

Methods: We created a decision analytic model comparing the costs and effects of platinum combination chemotherapy with personalized therapy in which patients with EGFR mutation-positive tumors were treated with erlotinib. We used two testing strategies: testing only those with tissue available and performing a repeat biopsy if tissue was not available versus three nontargeted chemotherapy regimens (ie, carboplatin and paclitaxel; carboplatin and pemetrexed; and carboplatin, pemetrexed, and bevacizumab).

Results: Compared with a carboplatin plus paclitaxel regimen, targeted therapy based on testing available tissue yielded an incremental cost-effectiveness ratio (ICER) of $110,644 per quality-adjusted life year (QALY), and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Probabilistic sensitivity analysis revealed substantial uncertainty around these point estimates. With a willingness to pay of $100,000 per QALY, the testing strategy was cost effective 58% of the time, and the rebiopsy strategy was cost effective 54% of the time. Personalized therapy with an EGFR TKI was more favorable when the nontargeted chemotherapy regimen was more expensive. Compared with carboplatin, pemetrexed, and bevacizumab, ICERs were $25,547 per QALY for the testing strategy and $44,036 per QALY for the rebiopsy strategy.

Conclusion: Although specific clinical circumstances should guide therapy, our cost-effectiveness analysis supports the strategy of testing for EGFR mutations in patients with stage IV or recurrent adenocarcinoma of the lung, rebiopsying patients if insufficient tissue is available for testing, and treating patients with EGFR mutations with erlotinib as first-line therapy.
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September 2012

Breast cancer risk prediction and mammography biopsy decisions: a model-based study.

Am J Prev Med 2013 Jan;44(1):15-22

Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.

Background: Controversy continues about screening mammography, in part because of the risk of false-negative and false-positive mammograms. Pre-test breast cancer risk factors may improve the positive and negative predictive value of screening.

Purpose: To create a model that estimates the potential impact of pre-test risk prediction using clinical and genomic information on the reclassification of women with abnormal mammograms (BI-RADS3 and BI-RADS4 [Breast Imaging-Reporting and Data System]) above and below the threshold for breast biopsy.

Methods: The current study modeled 1-year breast cancer risk in women with abnormal screening mammograms using existing data on breast cancer risk factors, 12 validated breast cancer single-nucleotide polymorphisms (SNPs), and probability of cancer given the BI-RADS category. Examination was made of reclassification of women above and below biopsy thresholds of 1%, 2%, and 3% risk. The Breast Cancer Surveillance Consortium data were collected from 1996 to 2002. Data analysis was conducted in 2010 and 2011.

Results: Using a biopsy risk threshold of 2% and the standard risk factor model, 5% of women with a BI-RADS3 mammogram had a risk above the threshold, and 3% of women with BI-RADS4A mammograms had a risk below the threshold. The addition of 12 SNPs in the model resulted in 8% of women with a BI-RADS3 mammogram above the threshold for biopsy and 7% of women with BI-RADS4A mammograms below the threshold.

Conclusions: The incorporation of pre-test breast cancer risk factors could change biopsy decisions for a small proportion of women with abnormal mammograms. The greatest impact comes from standard breast cancer risk factors.
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January 2013

The influence of health care policies and health care system distrust on willingness to undergo genetic testing.

Med Care 2012 May;50(5):381-7

Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: As the potential role of genetic testing in disease prevention and management grows, so does concern about differences in uptake of genetic testing across social and racial groups. Characteristics of how genetic tests are delivered may influence willingness to undergo testing and, if they affect population subgroups differently, alter disparities in testing.

Methods: Conjoint analysis study of the effect of 3 characteristics of genetic test delivery (ie, attributes) on willingness to undergo genetic testing for cancer risk. Data were collected using a random digit dialing survey of 128 African American and 209 white individuals living in the United States. Measures included conjoint scenarios, the Revised Health Care System Distrust Scale (including the values and competence subscales), health insurance coverage, and sociodemographic characteristics. The 3 attributes studied were disclosure of test results to the health insurer, provision of the test by a specialist or primary care doctor, and race-specific or race-neutral marketing.

Results: In adjusted analyses, disclosure of test results to insurers, having to get the test from a specialist, and race-specific marketing were all inversely associated with willingness to undergo the genetic test, with the greatest effect for the disclosure attribute. Racial differences in willingness to undergo testing were not statistically significant (P=0.07) and the effect of the attributes on willingness to undergo testing did not vary by patient race. However, the decrease in willingness to undergo testing with insurance disclosure was greater among individuals with high values distrust (P=0.03), and the decrease in willingness to undergo testing from specialist access was smaller among individuals with high competence distrust (P=0.03).

Conclusions: Several potentially modifiable characteristics of how genetic tests are delivered are associated with willingness to undergo testing. The effect of 2 of these characteristics vary according to the level of health care system distrust, suggesting that policy decisions about delivery of genetic testing may influence differences in uptake across patient subgroups defined by levels of distrust rather than by race.
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May 2012