Preferences for multigene panel testing for hereditary breast cancer risk among ethnically diverse BRCA-uninformative families

Abstract

Until recently, genetic testing for hereditary breast cancer has primarily focused on pathogenic variants in the BRCA1 and BRCA2 (BRCA) genes. However, advances in DNA sequencing technologies have made simultaneous testing for multiple genes possible. We examined correlates of interest in multigene panel testing and risk communication preferences in an ethnically diverse sample of women who tested negative for BRCA mutations previously but remain at high risk based on their family history (referred to as "BRCA-uninformative") and their at-risk female family members. Two-hundred and thirteen women with a previous breast cancer diagnosis and a BRCA-uninformative test result and their first-degree relatives completed a survey on interest in multigene panel testing, communication preferences, and sociodemographic, psychological, and clinical factors. Stepwise logistic regression was used to identify factors associated with testing interest. Chi-square analyses were used to test differences in risk communication preferences. Interest in multigene panel testing was high (84%) and did not considerably differ by cancer status or ethnicity. In multivariable analysis, factors significantly associated with interest in genetic testing were having had a mammogram in the past 2 years (odds ratio (OR) = 4.04, 95% confidence interval (CI) 1.80-9.02) and high cancer worry (OR = 3.77, 95% CI 1.34-10.60). Overall, the most commonly preferred genetic communication modes were genetic counselors, oncologists, and print materials. However, non-Hispanic women were more likely than Hispanic women to prefer web-based risk communication (p < 0.001). Hispanic and non-Hispanic women from BRCA-uninformative families have a high level of interest in gene panel testing. Cancer-related emotions and communication preferences should be considered in developing targeted genetic risk communication strategies.

Longitudinal outcomes with cancer multigene panel testing in previously testedBRCA1/2negative patients

“…Some patients expressed concerns about risk of distress and uncertainty, supporting the value of pretest counseling to ascertain patient preferences, particularly as the clinical utility of large panels remains unclear. In contrast to a recent study reporting high hypothetical interest in MGPT among BRCA1/2 negative participants, many patients in this study did not respond to the invitation to receive multigene panel testing. It is possible that uptake of testing after already completing prior BRCA1/2 testing is lower than when multigene panel testing is offered at initial testing, due to testing fatigue or other testing experiences.…”

Horizon Scan Of Clinical Laboratories Offering Pharmacogenetic Testing

“…52 Furthermore, patients who have received uninformative results from prior single-gene testing are more likely to be interested in multigene panel testing. 53,54 These data support speculations that large cancer susceptibility panels may eventually be replaced by whole genome or exome sequencing (despite their limited sensitivity), as use of these more comprehensive tests expands. 29…”

Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort

“…Since index cases of different ethnic backgrounds might be expected to present with different distributions/frequencies of variants and different distributions of personal and family histories of cancer, [13][14][15][16] we performed separate logistic regression analyses for each of four racial/ethnic groups: (1) Caucasian plus mixed or unknown race/ethnicity, (2) African American, (3) Asian, and (4) Hispanic. The predicted probabilities r k of carrying a pathogenic variant for each tested individual were then derived using the predict option in Stata.…”