When parents disclose BRCA1/2 test results: Their communication and perceptions of offspring response

Abstract

Background

BRCA1/2 testing is not recommended for children, as risk reduction measures and screening are not generally recommended before 25 years old (YO). Little is known about the prevalence and predictors of parent communication to offspring and how offspring respond to this communication.

Methods

Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least one child <25 YO. Logistic regressions were utilized to evaluate associations with communication. Framework analysis was utilized to analyze open-ended responses.

Results

253 parents completed interviews (61% response rate), reporting on 505 offspring. 29% of parents were BRCA1/2 mutation carriers. 334 (66%) offspring learned of their parent’s test result. Older offspring age (p<=0.01), offspring gender (female, p=0.05), parents’ negative test result (p=0.03) and parents’ education (high-school only, p=0.02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). 13% 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.

Conclusion

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 lifespan.

INTRODUCTION

In medicine today, there is an increasing expectation that scientific advances in genomics will provide opportunities to inform personalized medical recommendations for the treatment and prevention of disease^1-3. BRCA1/2 testing is an example of how genetic testing can be utilized to provide individualized recommendations for disease prevention^3-6. Adults with personal or family histories suggestive of hereditary breast and ovarian cancer are candidates for BRCA1/2 testing, which can inform risk reduction measures, such as early increased surveillance, chemoprevention and/or prophylactic surgery^7,8. BRCA1/2 mutation carriers are encouraged to inform other adult relatives of the alteration and the opportunity to undergo testing to identify relatives at increased risk. In addition, such testing would identify those who are not at increased risk, and thus, can follow general population screening guidelines^7,9.

Prophylactic surgery and radiographic screening for BRCA1/2 mutation carriers are generally not recommended until individuals are 25 years old (YO)^7,8. To date, there is no known medical benefit to communicating breast and ovarian cancer risk to offspring under the age of 18 YO^9,10, and professional societies have recommended against offering BRCA1/2 testing to children unless there is an immediate medical indication^9,11. Yet, debate continues regarding early communication of genetic risk and testing of children for adult-onset genetic disorders^12-20. Ethical and clinical arguments have identified potential advantages and disadvantages to early communication of genetic risk to at-risk minor children, although there is no empiric data to support either early communication of genetic risk to at-risk offspring or withholding such information until adulthood²¹.

There is evidence that many parents do share their genetic test results and the familial risk for cancer with minor at-risk children^22-27. This is perhaps not surprising given that parents are encouraged to, and do inform children of their parent’s cancer diagnosis^28-32. Several studies have suggested that adolescents are aware of and concerned about their own risk for cancer^33-37. Parents have reported disclosure of their BRCA1/2 mutation to children as young as 7 YO, and studies suggest that the majority of late adolescent and young adult offspring learn of the risk in the family^23-25.

Few studies have directly evaluated offspring understanding and psychosocial responses to early communication of familial risk^25,35,36. Interviews with a small cohort of adult offspring of BRCA1/2 mutation carriers, many of whom learned of their parents BRCA1/2 mutation during adolescence, suggests that many offspring appear to understand the risk communicated by their parent³⁶. Similar to parent reports²⁵, some offspring reported negative reactions to parental communication of familial risk, although many reported that they were not surprised by the information and did not find it distressing³⁶. Additionally, many offspring reported changing their health behaviors in response to parental communication of the familial risk³⁶.

To further explore communication to minor and young adult offspring among parents at risk for hereditary breast cancer, we have been expanding a cohort of parents who received BRCA1/2 testing and had at least one child under 25 YO at the time of testing. We hypothesized that parents who had a negative test result and those with older children would be more likely to share their genetic test results. Based on limited data in a cohort of BRCA1/2 mutation carriers^25,36, we further hypothesized that parent reports of offspring reactions might also vary by parent test result, and offspring age and gender.

MATERIALS AND METHODS

Participants

Institutional Review Board approval was obtained before initiating this study. Participants were recruited through the University of Chicago Cancer Risk Clinic and the Fox Chase Cancer Center Risk Assessment Program between February 2004 and July 2009. Eligible participants included those who had undergone BRCA1/2 genetic testing and had one or more offspring under age 25 at the time they received their genetic test result. All participants underwent pre-test and post-test genetic counseling. Informed consent was obtained by research staff prior to conducting telephone interviews.

Survey Instrument

A 31-item semi-structured interview was developed by the investigators to evaluate parent communication of BRCA1/2 test results to offspring and opinions regarding the genetic testing of minors^25,38. The interview employed structured (yes/no) and open-ended questions to assess parental disclosure for each eligible child (yes/no), timing of disclosure (open-ended) and parent perceptions of offspring’s initial reaction to the disclosed information (open-ended).

Statistical Analyses

Framework analysis was utilized to analyze open-ended responses^39-43. Investigators first intensively reviewed participant responses for a subsample (20%) of participants and developed a thematic framework for each open-ended item. Next, two investigators (AB, LPM) independently assigned thematic codes to the subsample’s open-ended responses regarding parents’ perceptions of offspring reactions to communication of parents’ BRCA1/2 test results (inter-coder agreement 98%). The thematic framework was then applied to the remaining sample and refined to include new themes as they emerged. Responses could be coded for more than one theme. Differences in code assignments were resolved through inter-coder discussion, which established agreement for all responses. Descriptive statistics were utilized to generate response proportions to close-ended items and coded data.

To investigate differences in disclosure to offspring by offspring age and parent test result, we used logistic regressions of disclosure fit by Generalized Estimating Equations (GEE) to account for within parent correlation of responses among children⁴⁴. Similarly, we used multiple logistic regressions fit by GEE to evaluate the multivariable associations among biomedical factors and demographic factors and disclosure to offspring.

RESULTS

Participant characteristics

Four hundred eighteen eligible parents were contacted to participate and 253 (61%) completed the telephone interview. Forty-nine individuals actively declined participation and 116 failed to participate after multiple contact attempts. Parent and offspring characteristics are described in Table 1. The 253 participants are from 232 unrelated families. The median time from parent receipt of genetic test result to interview was 21 months. Seventy-five percent of parents had received results within 3 years. At the time of parent genetic testing, participants had a total of 505 offspring under 25 YO.

Table 1.

Participant and offspring characteristics

	No. (%)
Parent characteristics (n=253)
Age, years
Mean (SD)	47.7 (6.8)
Median (range)	48 (28-66)
Gender
Women	241 (95)
Men	12 (5)
Parent test result
True positive	73 (29)
True negative	14 (6)
Uninformative negative	143 (57)
VUS	23 (9)
Race/Ethnicity
White	232 (92)
Black	13 (5)
Other	8 (3)
Marital status
Married	218 (86)
Education
High-school or less	24 (9)
Some college	51 (20)
College degree	86 (34)
Graduate education	92 (36)
Personal history of cancer***
Yes	169 (67)
No	84 (33)
History of prophylactic surgery among female parents (n= 241)
Mastectomy	52
Oophorectomy	90
Risk assessment program
University of Chicago	163 (64)
Fox Chase Cancer Center	90 (36)
Mean number relatives with cancer*(SD)	2.0 (1.5)
Median (range)	2.0 (0-8)
Mean earliest cancer in the family** (SD)	42.4 (8.9)
Median (range)	41.0 (24-78)
Offspring Characteristics (n=505)
Age at parent interview, median (range)	17 (3-35 YO)
Less than 10 years old	81 (16)
10-13 years old	88 (17)
14-17 years old	93 (18)
18 and older	243 (48)
Age at parent testing, median (range)	15 (<1 – 25 YO)
Less than 10 years old	133 (26%)
10-13 years old	92 (18%)
14-17 years old	96 (19%)
18-25 years old	184 (36%)
Gender
Female	253(50)
Male	252(50)
Parent test result
True positive	155 (29)
True negative	29 (6)
Uninformative negative	278 (57)
VUS	43 (9)

^*Breast and/or ovarian cancer

^**Including proband, first-degree and second-degree relatives

^***Any cancer excluding non-melanoma skin cancer

Rates of parental disclosure of BRCA1/2 test results to offspring

Among 505 offspring, 334 (66%) were reported by parents to have learned of their parent’s test result. Although the majority of parents (84%) reported sharing this information within 1 month of learning their result, 39 (12%) delayed sharing results with offspring (range 1mo – 6 years). The median age at disclosure of offspring who learned of their parent’s test result within 1 month of parent disclosure was 18 YO, compared to offspring disclosed to 1 -12 months (13 YO), or > 12 months (14 YO) after parent disclosure (p=0.006). Sixty-two percent of offspring of parents with a negative result were reported to have been disclosed to within 1 month, while only 41% of offspring of positive parents were disclosed to within 1 month (p<0.001). There was no statistically significant difference in communication delay by offspring gender.

Disclosure rates by offspring age are described in Table 2. Offspring event age (offspring age when their parent disclosed parent’s test results to offspring, or if parent did not disclose their test result to offspring, the age of child at study interview), was used to best characterize offspring age at the time offspring learned of their parent’s BRCA1/2 test result²⁵. The majority of offspring over 14 YO, and approximately half of children 10-13 YO, learned of their parents BRCA1/2 test result. Mean offspring age at parental disclosure of test results was 17.04 YO (SD 4.80, range 4-25 YO).

Table 2.

Disclosure rates among offspring according to offspring age (n= 505)

Offspring Age	Disclosure by offspring age at interview No. disclosed/offspring (%)	Disclosure by offspring event age* No. disclosed/offspring (%)
Under 10 years old	8/81 (10%)	24/97 (25%)
10-13 years old	40/88 (45%)	59/108 (55%)
14-17 years old	62/93 (67%)	78/108 (72%)
18-25 years old	224/243 (92%)	173/192 (90%)

^*Offspring event age = age at disclosure if disclosure occurred or at interview if no disclosure occurred

Predictors of parental disclosure of BRCA1/2 test results to offspring

Prevalence of reported parental disclosure of BRCA1/2 test results to offspring varied significantly by parent test result (Fig 1a) and offspring event age (age of offspring at disclosure or age of offspring at interview if no disclosure occurred) (Fig 1b). Given the relatively smaller number of offspring of parents with a true negative result (TN, i.e. negative for a known BRCA1/2 mutation in the family) or variant of uncertain significance (VUS), all negative results were combined for multivariable analyses. In a single multivariable model, older offspring event age (p<=0.01), female offspring gender (p=0.05), parents’ negative test result (p=0.03) and parents’ lesser education (high-school only, p=0.02) were significantly associated with communication of genetic test results to offspring (Table 3). We ran separate multivariable models to evaluate factors associated with disclosure by parent test result. Offspring event age remained significantly associated with parental disclosure to offspring (p < .01). Female offspring gender was significantly associated with disclosure among offspring of parents with negative test results (p=0.05) and not among offspring of parents with a positive BRCA1/2 test result.

Fig 1.

a. Parent disclosure of BRCA1/2 test results by parent test result (n=505 offspring)

*p-value=0.015 for hypothesis test of general difference in disclosure rates among genetic test result groups using Wald test from GEE-fit logistic regression.

TN = true negative test result, UN = uninformative negative test result (negative mutation without a known BRCA1/2 mutation in the family), VUS = variant of uncertain significance, POS = BRCA1/2 mutation

b. Parental disclosure of BRCA1/2 test results by offspring event age* (n=505 offspring)

*offspring age when their parent disclosed parent’s test results to offspring, or if parent did not disclose their test result to offspring, the age of child at study interview

**p-value<0.001 for hypothesis test of general difference in disclosure rates among age groups using Wald test from GEE-fit logistic regression.

Table 3.

Associations between parent/offspring characteristics and disclosure by multivariable models (n = 492 children^**)

	ALL participants (n=492)			BRCA1/2 positive (n=155)			BRCA1/2 negative (n=337)
	OR	95% CI	p	OR	95% CI	p	OR	95% CI	p
Child event age*
<10	-	-	-	-	-	-	-	-	-
10-13	2.8	1.7-4.6	<0.01	2.7	1.0-7.1	0.05	3.1	1.6-5.9	<0.01
14-17	5.0	2.8-8.9	<0.01	4.7	1.6-13.7	0.01	5.1	2.5-10.6	<0.01
18-24	20.9	10.2-42.8	<0.01	25.4	6.8-95.2	<0.01	19.0	7.6-47.5	<0.01
Parent test result
Negative	2.4	1.1-5.4	0.03	-	-	-		-	-
-
Parent gender
Mother	3.9	0.9-18.1	0.08	1.9	0.2-16.6	0.55	6.6	0.6-71.3	0.12
Offspring gender
Daughter	1.5	1.0-2.2	0.05	1.3	0.6-2.6	0.51	1.7	1.0-2.8	0.05
Parent education level
HS only	4.8	1.3-17.2	0.02	4.5	0.9-22.5	0.07	6.3	0.5-80.0	0.16
Parent race
White	2.1	0.7-5.3	0.14	0.6	0.1-5.8	0.68	2.9	1.0-8.8	0.06
Parent cancer history
Had cancer	1.4	0.7-2.8	0.36	1.1	0.3-3.7	0.84	1.9	0.8-4.6	0.18
History of prophylactic mastectomy (females only)
Yes	1.4	0.7-2.9	0.37	2.7	0.8-8.9	0.11	0.9	0.3-2.4	0.82
History of prophylactic oophorectomy (females only)
Yes	1.3	0.6-2.8	0.48	1.3	0.3-5.3	0.75	1.2	0.5-3.2	0.68
No. relatives with cancer
	1.0	0.8-1.2	0.95	0.8	0.5-1.1	0.16	1.2	0.9-1.6	0.18
Age earliest cancer in the family
	1.0	1.0-1.1	0.11	1.0	1.0-1.1	0.41	1.0	1.0-1.1	0.20

HS = high school

OR = odds ratio

^*Event age = offspring age when their parent disclosed parent’s test results to offspring, or if parent did not disclose their test result to offspring, the age of child at study interview

^**13 offspring excluded for incomplete data (11 missing youngest age of cancer in the family and 2 missing total FDR/SDR with cancer)

Parent perceptions of their children’s reactions to learning their of their parent’s BRCA1/2 test results

Parents who reported disclosure to offspring (n=182 parents) were asked to describe their perceptions of their offspring’s initial response to learning of their parent’s BRCA1/2 test result. The most frequently described offspring responses were neutral (41%), and/or happiness or relief (28%) (Table 4). Examples of neutral responses include: “They just took in the information and had no comments” (17 YO and 20 YO daughters of a mother with a BRCA1/2 mutation) and “they had no real reaction” (10 YO and 12 YO sons of mother with an uninformative negative result). Some parents reported offspring concern (13% of offspring) after sharing their BRCA1/2 test results, including concern for parents (n=24), themselves (n=15), in general (n=9), and other family members (n=1). “She just wanted to know if mommy is going to be ok” (16 YO daughter of mother with an uninformative negative result), and “she was concerned, and hopeful that she doesn’t have the mutation” (15 YO daughter of a mother with a BRCA1/2 mutation). By parent report, a small percentage (11%) of offspring expressed distress (upset, scared, avoidant or fatalistic) in response to parental communication. “They were upset and scared. She thinks every ache and pain means she has cancer”.” He doesn’t want to know his genetic risk for cancer” (19 YO daughter 16 YO son of mother with BRCA1/2 mutation), “She was not relieved. She still feels doomed to get breast cancer” (18 YO daughter of a mother with an uninformative negative result). Some parents reported that their offspring appeared to not understand the information (7%), asked questions or were curious (5%), and/or appreciated the information or found it useful (4%).

Table 4.

Parent perceptions of offspring initial reactions to communication of parent BRCA1/2 test results^* (n= 328 offspring)

Coded response*	All n = 328	Parent positive n = 84	Parent Negative n = 244
	n (%)	n (%)	n (%)
Neutral	136 (41)	25 (30)	111 (44)
Relief, happiness	91 (28)	0 (0)	91 (37)
Concern	43 (13)	28 (33)	15 (6)
Upset, scared, avoidant or fatalistic	37 (11)	18 (21)	19 (8)
Didn’t understand	24 (7)	12 (14)	12 (5)
Had questions	16 (5)	2 (2)	14 (6)
Found information useful	15 (5)	5 (6)	10 (4)

^*Responses could be coded for more than one theme. Responses reported at frequencies < 5 not reported.

We conducted separate exploratory analyses to evaluate parents’ perceptions of offspring responses by parent test result, offspring age, and offspring gender. Perceived offspring reactions varied by parent test result (Fig 2a). As might be expected, reports of relief were exclusively reported among offspring not learning of a positive result. Reports of concern among offspring were most frequently reported for offspring learning of a parent’s positive test result (Fig 2a). Parental perceptions of distress (upset, scared, avoidant or fatalistic) among offspring were more frequently reported for offspring learning of their parent’s positive result or VUS. Perceived offspring responses also varied by offspring age at disclosure (Fig 2b). Reports of offspring distress (upset, scared, avoidant or fatalistic), not understanding, and asking questions were more frequently reported for younger offspring (<10 YO). Parents most frequently reported offspring concern in older offspring (14-24 YO). Neutral responses and asking questions were more frequently reported of sons. While parents more frequently described distress among daughters, they also more frequently reported that daughters found the information useful compared to sons (Fig 2c).

Figure 2.

A. Perceived offspring responses by parent test result

TN = true negative test result, UN = uninformative negative test result (negative mutation without a known BRCA1/2 mutation in the family), VUS = variant of uncertain significance, POS = BRCA1/2 mutation

B. Perceived offspring responses by offspring age at disclosure

C. Perceived offspring responses by offspring gender

DISCUSSION

One of the primary motivations for BRCA1/2 testing for parents is to better understand the risk for their offspring⁴⁵, and studies have shown that many parents do communicate their BRCA1/2 test results to offspring^22-25,27. In this study, the largest study to date, the majority of parents reported telling their offspring older than 10 YO of their genetic test result. While prior studies have suggested that most late adolescent and young adult offspring learn of familial and genetic risk for breast and ovarian cancer, our study suggests that many offspring, even younger than 13 YO, also learn of their parent’s BRCA1/2 test results., Other studies have suggested no significant difference in disclosure rates among young (<13 YO) and late adolescents (14-17 YO)²² or late adolescents and young adults (18-25 YO)²⁴. Our study, which focused specifically on communication to children and young adult offspring, identifies disclosure rates that are significantly greater with increasing age, suggesting that age, or parental perception of a correlate of chronological age, such as physical development or psychosocial maturation, are contributors to parent decisions to share their BRCA1/2 test results with offspring. As suggested by others²⁶., and consistent with developmentalists’ recommendations for parent communication of a cancer diagnosis⁴⁶, parents might feel more confident that an older child can understand and benefit from the genetic test results. Additionally, offspring exposure to, and knowledge of, genetics as offspring mature might prompt offspring questions and discussion of the parent’s genetic test results.

Although prior studies have not shown a significant difference in disclosure among parents with a positive or negative test result^22-24, we found that offspring are more likely to learn of a parent’s negative than positive test result and daughters are more likely to learn of a negative result, independent of child age. This is not surprising given the different medical indications and testing opportunities (when reaching adulthood) for offspring of parents with negative and positive test results. Additionally, it has been hypothesized that parents respond differentially to health related issues by offspring gender only after offspring reach adolescence⁴⁷. Thus, it is possible that discussion of daughters’ risk becomes incorporated into other parent-daughter conversations surrounding puberty and breast development. While communication was significantly higher from parents to daughters than sons, this difference was significant among parents’ with negative, but not positive BRCA1/2 test results. It has been suggested that girls might be more perceptive of the physical cues of, and more emotionally challenged by puberty⁴⁸. Thus, parents with negative results might be more likely to share this information with daughters to offer health reassurance during puberty and given the implications of breast cancer for women. Similar to at least one study evaluating maternal communication of a breast cancer diagnosis to offspring, BRCA1/2 mutation carriers with less formal education were more likely to share their BRCA1/2 test results with offspring²⁸. Also similar to other studies^22,23, parental diagnosis of cancer in our study was not significantly associated with communication of genetic test results to offspring.

In an earlier study, we found that some parents with a BRCA1/2 mutation reported witnessing distress (26%) or concern (22%) in their offspring after sharing their BRCA1/2 test results with their offspring²⁵. In this larger study evaluating disclosure to 505 offspring and including parents with negative and positive results, parents reported fewer offspring having negative reactions to learning their parent’s genetic test result. Yet, parent reports of offspring responses did appear to vary by parent test result, offspring age and offspring gender, and rates of distress and concern among offspring learning of a parents’ positive BRCA1/2 mutation are consistent with our earlier study. Our data suggests that offspring learning of a parent’s positive or VUS result may be more likely to experience distress or have questions about parents’ result. Our data also suggest age-related differences in offspring responses, with distress more common in offspring under 10 YO, and concern more common in offspring between 14-24 years. More advanced cognitive development in older offspring might allow for more adaptive means of coping. As well, their more mature emotional regulation skills might allow them to appear less distressed than they feel, making it more difficult for parents to accurately gauge their reactions⁴⁶. We acknowledge that differences in parent reports of offspring response may also reflect parent factors (e.g. cancer specific distress, depression, cancer history)³². Thus, parent report of offspring response might not correlate highly with offspring responses^29,47,49-51. Direct evaluation of offspring’s psychosocial response is critical to provide an offspring-centered understanding of the risks and benefits of early parental communication of genetic risk for breast and ovarian cancer. Yet, understanding both parent and offspring perspectives is invaluable in understanding how parents perceive their offspring’s experience in receiving genetic or family risk information, and the resultant implications for developing interventions to facilitate communication of those undergoing genetic testing to offspring and other family members.

Although informative, we acknowledge several limitations to this study. Parents were asked to report on communication events and experiences that occurred retrospectively, which allow for potential recall bias. Our results only describe parents’ general perceptions of offspring reactions, which could not be expected to elucidate all of the parent and offspring factors that mediate and moderate those outcomes. Future longitudinal study, most importantly including interviews with offspring, can better inform the biopsychosocial impact of this communication on offspring psychosocial development, and behavioral and psychosocial adaptation over time⁴⁷. An additional limitation is that, as with most studies in families at increased risk of breast and ovarian cancer, participants who were recruited from specialized cancer risk clinics were highly educated, and minorities were underrepresented. Thus, these findings might not apply to a more diverse population of BRCA1/2 mutation carriers. It is also possible that participants in this study represent a population more likely to communicate to offspring than non-participants. The number of parents with a true negative result and VUS results were relatively small. It is possible that there are differences in communication among parents with true negative, VUS and uninformative negative results that could not be detected in this cohort. Given the different clinical implications of these results, future research evaluating these differences in a sample with greater representation among these subgroups could be valuable.

In conclusion, many parents report communicating their BRCA1/2 test results to their offspring even at young ages. The clinical impact of this communication remains unknown, however the rate of communication to children and adolescents is high, and the data suggest that a majority of offspring do not find this information distressing. Many health and risk behaviors that impact the morbidity and mortality of youths and adults begin in (e.g. tobacco and alcohol use, and sexual activity) or become established in (e.g. diet and exercise) adolescence ^52-54. If done effectively, early communication of hereditary risk provide a “teachable moment”, initiating or establishing risk reductive behaviors^36,54. A better understanding of how children, adolescents and young adults respond to and utilize information about hereditary risks for adult cancer, including genetic risk information such as BRCA1/2 status, and how those processes change developmentally into, during and out of adolescence has the potential to provide opportunities to facilitate protective health behaviors in adolescence and throughout the lifespan that have the potential to reduce the morbidity and mortality of BRCA1/2-assocaited and other hereditary cancers throughout the lifespan.