Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk
Reporter/Curator: Stephen J. Williams, Ph.D.
Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing[1]
Direct-to-consumer (DTC) genetic testing and genetic health information in 2007 with the advent of personalized testing services by companies who offered microarray-based genotyping of single-nucleotide-polymorphisms (SNP) which had strong correlations to disease risk. Three companies started to offer such services directly to the consumer:
A common test which is offered analyzes the consumers BRCA1/2 mutation status. Three mutations in the BRCA gene are known to predispose women to hereditary breast and ovarian cancer: BRCA1 185delAG, BRCA1 538insC, and BRCA2 617delT. These BRCA1 mutation confer a 60% breast cancer risk and a 40% risk of ovarian cancer while the BRCA2 mutation confers a breast cancer risk of 50% and 20% risk of ovarian cancer.
However, the commercial availability of this genetic disease-risk associated testing has led to certain ethical issues concerning communication and responses of risk information by:
- Consumers who request BRCA1/2 testing (focus of the Francke article
- BRCA1/1 testing and communication of results to minors and relatives (Bradbury: see below)
There has been much opinion, either as commentary in literature, meeting proceedings, or communiques from professional societies warning that this type of “high-impact” genetic information should not be given directly to the consumer as consumers will not fully understand the information presented to them, be unable to make proper risk-based decisions, results could cause panic and inappropriate action such as prophylactic oophorectomy or unwarranted risk-reduction mastectomy, or false reassurance in case of negative result and reduced future cancer screening measures taken by the consumer. However, there have been few studies to investigate these concerns.
A report by Dr. Uta Francke in the open access journal PeerJ, assesses and quantifies the emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service® report of the three BRCA mutations known to be associated with high risk for breast/ovarian cancer. One hundred thirty six (136) individuals, who tested positive for BRCA1 and/or BRCA2 mutations as well as 160 users of the service, who tested mutation-free were invited to participate in phone interviews addressing personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of results, emotional responses, perception of personal cancer risk, information sharing, and actions taken. Thirty two (32) mutation carriers (16 female and 16 male) and 31 non-carriers responded to the phone questionnaire.
Questions were based on the following themes:
- When you purchased the 23andME Personal Genome Service® were you aware that it included testing for mutations that predispose to breast and ovarian cancer?
- Were you aware that having Ashkenazi Jewish ancestry influences your risk of carrying one of the three mutations?
- Have you or a first or second degree relative been diagnosed with breast, ovarian or any other cancer?
- What did you learn from your results?
- Were you surprised by the result?
- How did you feel about this information (extremely, moderately, somewhat upset or extremely relieved)?
Results: Eleven women and 14 men had received an unexpected result that they are carriers of one of the three mutations however none of them reported extreme anxiety and only four reported moderate anxiety which did not last long. Participants were at least 8 years of age. Five women and six men described their reaction as neutral. Most carrier women sought medical advice and four underwent risk-reducing procedures. Some to the male carriers felt burdened to share their test results with their female relatives, which led to additional screenings of relatives. Almost all of the mutation-positive customers appreciated learning their BRCA mutational status.
Other highlights of the results include:
- More women got tested if they had a first or second degree relative previously diagnosed with breast/ovarian cancer
- Ten mutation-positive individuals who were surprised at the test results cited the lack of family history of breast/ovarian cancer as the reason for their surprise. The rest who were surprised at their positive test results believed that the frequency of these mutations were low in the general population so they shouldn’t have been affected.
- For the mutation-positive group, none of the 32 reported as being “extremely upset”.
- Interestingly, on male who learned, for the first time, he was a positive carrier for BRCA mutation, reported feeling “relieved” because his daughter who was also tested by 23andMe had not acquired his mutation.
A brief interview with Dr. Francke follows:
Q: In your results you had noted that none of the mutation carriers showed extreme anxiety about their reports however there were many of Ashkenazi descent who was well aware of the increased risk to breast cancer. In another study by Dr. Angela Bradbury, anxieties and communication to their children depended on mutation status and education status. Do you feel that most women in your study were initially aware they could be in a high risk category for cancer, whether breast, ovarian, or other?
Dr. Francke: As we show in Table 1, 6 of 16 women and 6 of 16 men who found out that they were BRCA mutation carriers had not been aware that being of Ashkenazi descent confers an increased risk of breast/ovarian cancer. In Table S1, we show that 6 of these 32 people did not self-identify as Ashkenazi.
Q: The reporting and communication of test results to offspring and genetic testing of offspring as a result of positive tests has been under much debate. I had noticed that there was a high proportion of relatives who went for screening after learning of a family members BRCA testing, whether it showed a mutation or not. Some studies have shown that offspring of carriers may misinterpret genetic testing results and take inappropriate action, such as considering having early testing before age 25. It appears some anxiety may be due to misinformation and lack of genetic counseling. Should these test results be considered in guidelines for oncologist such as NCCN guidelines with respect to informing family members using genetic counselors as an intermediary?
Dr. Francke: The “high proportion of relatives who went for screening after learning of a family member’s BRCA testing”, were only those related to a BRCA-positive person. Most of the BRCA testing of relatives was done through health care providers at Myriad as these people were eligible for insurance coverage of the test. In our interviews we found no evidence for inappropriate action of carriers or non-carriers. With one exception, we found no evidence for misinterpretation or “anxiety due to lack of genetic counseling”. In our online reports we recommend genetic counseling for all customers who have questions about their results.
Q: I was also particularly interested the male carrier felt a heightened burden to tell their offspring. This has been suggested in other studies. I would assume the mothers and not the fathers would feet more pressure to tell their children. Is there a reason for this?
Dr. Francke: The heightened burden reported by the male carriers was mostly about the realization of the risk for their daughters, not so much about to telling their offspring. Female carriers were primarily concerned about their own health risk and management, and decision-making about preventive measures – therefore, the risk for offspring appeared to be of secondary concern for them.
However, the availability of this type of predictive genetic testing for hereditary cancer has raised some ethical issues regarding the communication of risk and genetic results to family members and especially offspring, specifically whether informing minors would incur unnecessary testing, anxiety among minors of parents who tested positive for genetic risk-factors, or even premature risk-reduction surgeries or medical interventions.
The aforementioned ethical issues concerning communicating results of BRCA mutational testing to offspring was addressed by two large studies conducted by Dr. Angela Bradbury M.D. and colleagues at Fox Chase Cancer Center Family Risk Assessment Program (now she is at University of Pennsylvania) and University of Chicago Cancer Risk Clinic. These studies evaluated the parental opinions regarding BRCA1/2 testing of minors, and how parents communicate BRCA1/2 genetic testing with their children.
In the JCO article (Parent Opinions Regarding the Genetic Testing of Minors for BRCA1/2)[2], Bradbury and colleagues used semistructured interviews (yes/no questions and open-ended questions) of 246 parents at Fox Chase and University of Chicago, who underwent BRCA1/2 whether they supported testing of minors in general and testing of their own offspring. Parents were asked, “If you were deciding, do you think children under 18 years old should be given the opportunity to be tested” and followed by the open-ended question: “Why do (don’t) you support the genetic testing of minors for BRCA1/2?”.
Results: In response to the first question (Would you support testing in minors) 37% of parents supported testing of minors in the general population. The follow-up open-ended question revealed that 4% support testing minors in some or all circumstances. This decision was independent of parent sex or race. 44% of parents would test their own offspring. Parents who opposed testing in minors thought testing would cause fear and anxiety for their children but those who supported unconditional testing (regardless of whether they were positive for the BRCA mutation or not) mentioned that the medical information would foster better health behaviors in their offspring. 21% of parents who opposed testing minors, in general, actually supported testing of their own children. Interestingly parents who tested positive for the BRCA1 overwhelmingly (64%) opposed testing of minors, in general. In addition, statistical analysis of the open-ended questions revealed that parents who did not have a college degree, had a negative test result, and were non white favored testing of their own children. The authors had suggested larger studies before any guidelines were given as to whether testing in minors of BRCA mutation carriers should be standard.
In a recent publication by Dr. Bradbury and colleagues (Knowledge and perceptions of familial and genetic risks for breast cancer risk in adolescent girls)[3], studied how adolescent girls understood and responded to breast cancer risk by interviewing 11-19 year-old girls at high-risk and population-risk for breast cancer. Although most girls said they were aware of increased risk because either a family member had or was predisposed to breast cancer (66 %) only 17 % of girls were aware of BRCA1/2 genes. Mother was the most frequently reported source of information for breast cancer among both high-risk (97 %) and population-risk (89 %) girls. The study also showed that most girls who believe they are at high-risk could alter their lifestyles or change dietary habits to lower their risk.
In an adjacent study in the journal Cancer[4], Bradbury and colleagues at Fox Chase Cancer Center had gauged the frequency with which parents had told their children of their BRCA1/2 teat results and how their children felt about the results.
When parents disclose BRCA1/2 test results: Their communication and perceptions of offspring response[4]
Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least 1 child <25 YO. A total of 253 parents completed interviews (61% response rate), reporting on 505 offspring. Twenty-nine percent of parents were BRCA1/2 mutation carriers. Three hundred thirty-four (66%) offspring learned of their parent’s test result. Older offspring age (P ≤ .01), offspring gender (female, P = .05), parents’ negative test result (P = .03), and parents’ education (high school only, P = .02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). Thirteen percent of offspring were reported to experience concern or distress (11%) in response to parental communication of their test results. Distress was more frequently perceived among offspring learning of their parent’s BRCA1/2 positive or variant of uncertain significance result.
CONCLUSIONS:
Many parents communicate their BRCA1/2 test results to young offspring. Parents’ perceptions of offspring responses appear to vary by offspring age and parent test result. A better understanding of how young offspring respond to information about hereditary risk for adult cancer could provide opportunities to optimize adaptive psychosocial responses to risk information and performance of health behaviors, in adolescence and throughout an at-risk life span.
Below is an excellent article by Steven Reinberg from HealthDay interviewing Dr. Angela Bradbury concerning their JCO study: (reported for ABC News at http://abcnews.go.com/Health/Healthday/story?id=4508346&page=1#.UVNJUVef2RM)
Many Parents Share Genetic Test Findings With Kids
By Steven Reinberg
HealthDay Reporter
Mar. 23
FRIDAY, Aug. 17 (HealthDay News) — As genetic testing for diseases becomes more commonplace, the impact of those findings on family members may be underestimated, researchers say.
For instance, some women who discover they have the BRCA gene mutation, which puts them at higher risk for breast cancer, choose to tell their children about it before the children are old enough to understand the significance or deal with it, a new study found.
“Parents with the BRCA mutation are discussing their genetic test results with their offspring often many years before the offspring would need to do anything,” said study author Dr. Angela Bradbury, director of the Fox Chase Cancer Center’s Family Risk Assessment Program, in Philadelphia.
According to Bradbury, more than half of parents she surveyed told their children about genetic test results. Some parents reported that their children didn’t seem to understand the significance of the information, and some had initial negative reactions to the news.
“A lot of genetic information is being shared within families and there hasn’t been a lot of guidance from health-care professionals,” Bradbury said. “While this genetic risk may be shared accurately, there is risk of inaccurate sharing.”
In the study, Bradbury’s team interviewed 42 women who had the BRCA mutation. The researchers found that 55 percent of parents discussed the finding and the risk of breast cancer with at least one of their children who was under 25.
Also, most of the women didn’t avail themselves of the services of a doctor or genetic counselor in helping to tell their children, Bradbury’s group found.
Bradbury is concerned that sharing genetic information with young children can create anxiety. “The children could be overly concerned about their own risk at a time when there is nothing that they need to do,” she said.
But, she added, “it may be possible that sharing may be good for children in adapting to this information.”
The findings are published in the Aug. 20 issue of the Journal of Clinical Oncology.
The lack of definitive data on when — or if — to discuss genetic test results with children is a real problem, Bradbury said.
“As we move genetic testing forward for cancer or other illnesses, we have to consider the context of the whole family and focus our counseling to the whole family, and not just the person who comes in for testing,” Bradbury said. “We should learn more about how and when we should talk to children about this, so that we can promote healthy behaviors without causing too much anxiety for the offspring.”
Barbara Brenner, executive director of Breast Cancer Action, agreed that the psychological component of genetic testing needs more attention.
“This is the tip of a very scary iceberg,” Brenner said. “We don’t know the psychological consequences [of BRCA testing], not only to the person who has the test, but to her family members.”
Brenner thinks guidelines to help parents deal with this information are needed. So is help from doctors and genetic counselors in counseling family members, especially children, she added.
LEGACY (Lessons in Epidemiology and Genetics of Adult Cancer from Youth), supported by the National Institutes of Health. This study will follow the girls prospectively in order to evaluate epidemiologic and epigenetic pathways of childhood exposures in relation to pubertal development, age at menarche, breast tissue characteristics, biomarkers of exposure, genomic DNA methylation, and the psychosocial impact of increased breast cancer susceptibility in 6-13 YO girls. http://legacygirlsstudy.org/
1. Francke U, Difamco C, Kiefer AK, Eriksson N, Moiseff B, Tung JY, Mountain JL: Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing. PeerJ 2013:1-21.
2. Bradbury AR, Patrick-Miller L, Egleston B, Sands CB, Li T, Schmidheiser H, Feigon M, Ibe CN, Hlubocky FJ, Hope K et al: Parent opinions regarding the genetic testing of minors for BRCA1/2. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010, 28(21):3498-3505.
3. Bradbury AR, Patrick-Miller L, Egleston BL, Schwartz LA, Sands CB, Shorter R, Moore CW, Tuchman L, Rauch P, Malhotra S et al: Knowledge and perceptions of familial and genetic risks for breast cancer risk in adolescent girls. Breast cancer research and treatment 2012, 136(3):749-757.
4. Bradbury AR, Patrick-Miller L, Egleston BL, Olopade OI, Daly MB, Moore CW, Sands CB, Schmidheiser H, Kondamudi PK, Feigon M et al: When parents disclose BRCA1/2 test results: their communication and perceptions of offspring response. Cancer 2012, 118(13):3417-3425.
Sources:
http://abcnews.go.com/Health/Healthday/story?id=4508346&page=1#.UVNJUVef2RM
Other article on Ethics and Personalized Medicine on the site include:
2012pharmaceutical
Amandeep Kaur
Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aptubman
Arav Gandhi
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Dror Nir
dsmolyar
Ethan Coomber
evelinacohn
Gail S Thornton
Irina Robu
jayzmit48
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
Madison Davis
marzankhan
megbaker58
ofermar2020
Dr. Pati
pkandala
ritusaxena
Rick Mandahl
sjwilliamspa
Srinivas Sriram
stuartlpbi
Dr. Sudipta Saha
tildabarliya
zraviv06
zs22