return of results, confidentiality, research ethics committees, cancer, genetic testing, cancer patients, family members
Advances in genome sequencing technology have led to many new discoveries about the molecular biology of cancer. These advances have been made possible through the participation of cancer patients and their family members. Whether and when to inform research participants (and their asymptomatic relatives) about individual-level study findings remains a topic of debate. In an effort to anticipate some of the complexities associated with returning research results and to support enrollment decision-making among potential participants, genetic counseling is often offered to potential participants before informed consent discussions and genetic testing.1,2
A researcher in a developing country in Southeast Asia conducted a genomic study on hereditary breast and ovarian cancer.3 The project planned to recruit clinic patients who had: 1) ovarian cancer, 2) breast cancer diagnosed before 45 years of age; 3) two primary breast cancers, both diagnosed before 60 years of age, 4) triple-negative breast cancer (i.e., cancer cells that do not have estrogen or progesterone receptors and do not produce much if any of the HER2 protein) diagnosed before 60 years of age, or 5) male breast cancer. Genetic tests were performed free of charge for participants,4 and results were deidentified before analysis. The research ethics committee (REC) approved the decision that individual study results would not need to be returned to participants because of a lack of data about potential benefits of the findings.
The research determined that some of the participants had mutations in BRCA1 or BRCA2, genes which are linked with hereditary breast and ovarian cancer. A few of the participants did develop additional tumors in their remaining breasts or ovaries, and some relatives of participants developed breast and ovarian cancers. The findings generated news interest. Simultaneously, a famous American actress (Angelina Jolie) announced publicly that she had both breasts removed due to presence of a BRCA1 gene mutation and a family history of breast and ovarian cancer (her mother and maternal aunt) despite not having cancer herself. Increased public awareness of the potential benefit of genetic testing for BRCA1 and BRCA2 prompted the research team to ask the REC to allow them to provide research results to patients who had participated in the study.
After a detailed review of the situation and new findings, the REC approved of the change along with genetic counseling. At that time, some of the patients who participated in the study had died, but surviving spouses were asked to provide consent for the results to be disclosed to all first-degree relatives. Other participants agreed to learn their test results as well as to be monitored clinically to watch for the possible development of cancer. In addition, some of the patients’ relatives also chose to have genetic testing done after genetic counseling.
Questions
Did the REC originally make the wrong decision to not have the study return significant test results to the study participants? Is it appropriate that they changed their mind midway through the study?
Joining a research study like this may provide patients from lower socio-economic backgrounds access to free genetic testing, which can otherwise be quite costly. Does this pose any ethical issue? Why or why not?
Genomic research results are of potential interest not only to research participants but also biological family members. What ethics considerations are relevant to researchers when deciding whether or not to share results with biological family members after a participant's death?
