||5R01CA223606-03 Interpret this number
||Facilitated Education and Testing in Brca Positive Families
Genetic counseling and testing typically starts with a family member who is affected with breast or ovarian
cancer. If a pathogenic variant (PV) is identified in this `index patient,' then she is encouraged to communicate
with her at-risk relatives. First- and second-degree relatives of this index patient are at 50% and 25% risk for
carrying the same PV. Undergoing targeted genetic testing for this variant has enormous potential benefits -
particularly for those who have not been affected with cancer. Women who inherit a PV in BRCA1/2 are at 55-
70% risk of developing breast cancer and 16-45% risk of developing ovarian cancer. Men who inherit a PV are
at increased risk for prostate, breast and pancreatic cancer. Learning that one carries the PV identified in the
family allows women to take definitive actions to reduce their cancer risk and allows men to participate in high-
risk surveillance programs recommended for male BRCA1/2 carriers. Further, men and women who learn that
they do not carry the familial PV, can avoid unnecessary risk reduction and screening interventions and
reassure their offspring that they are not at risk for carrying the familial PV. Despite these clear benefits, uptake
of genetic counseling is low and only 28-57% of first- and second-degree relatives undergo testing. This low
rate of genetic counseling and testing occurs despite high rates of communication. However, the accuracy and
quality of the information communicated is not clear and additional practical barriers to uptake are common.
Surprisingly, there have been no trials designed to improve the rate of uptake in this population. This
represents a missed opportunity to reduce morbidity, mortality and costs associated with a variety of cancers.
Observational studies suggest that direct contact from the genetics provider including Web resources and
clinical referral is associated with higher counseling and testing uptake. These findings along with the low
uptake in current clinical practice underscore the need to improve the standard approach for identifying,
educating and testing relatives from hereditary breast ovarian cancer families. In the proposed randomized
controlled trial, we will test a combination intervention which provides Web-based pre-test education and
streamlined telephone-based genetic counseling (W+T) to first- and second-degree relatives of individuals who
have recently received a positive BRCA1/2 test result. We will recruit 426 first- and second-degree relatives
who have a 25-50% chance of carrying a PV and randomize them to W+T vs. Usual Care (UC). We will
conduct a baseline survey prior to randomization and then follow-up surveys at 1- and 6-months post
randomization. Our primary outcomes are the uptake of genetic counseling and genetic testing. Secondary
outcomes include psychosocial outcomes, number of mutations detected and uptake of preventive/surveillance
behaviors. This study, which is guided by the Health Belief Model and the Informed Choice Model, will have
practical clinical significance through the development and evaluation of an intervention designed for
individuals at the highest level of risk, potentially yielding improved cancer outcomes.
Re: Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative.
, Isaacs C.
, Schwartz M.D.
Journal of the National Cancer Institute, 2019-08-01; 111(8), p. 872-873.