Decisional Outcomes of Maternal Disclosure of BRCA1/2 Genetic Test Results to Children

Abstract

Background

Although BRCA1/2 genetic testing is discouraged in minors, mothers may disclose their own results to their children. Factors affecting patients’ disclosure decisions and patient outcomes of disclosure are largely unknown.

Methods

Mothers (N = 221) of children ages 8-21 enrolled in this prospective study of family communication about cancer genetic testing. Patients underwent BRCA1/2 genetic counseling and testing, and completed standardized behavioral assessments prior to and 1-month following receipt of their results.

Results

Most patients (62.4%) disclosed BRCA1/2 test results to their child. Patients were more likely to disclose if they received negative or uninformative vs. positive results (OR = 3.11; 95% CI = 1.11 - 8.71; P = .03), their child was ≥ 13 years of age vs. younger (OR = 5.43; 95% CI = 2.18 - 13.53; P < .001), and as the ratio of patients’ perceived benefits of disclosure outweighed potential risks (OR = 2.40; 95% CI = 1.63 - 3.54; P < .001). Post-decision satisfaction about disclosure was lowest among nondisclosing patients (P < .001) and those reporting greater decisional conflict (P < .001).

Conclusions

Patients commonly discuss their BRCA1/2 results with their teenage and young adult children, especially if the information is perceived as beneficial. Satisfaction with disclosure decision-making remains lowest among nondisclosing and conflicted patients. Family communication decision support adjuncts to genetic counseling are needed to help ameliorate these effects.

Impact

This study describes the prevalence of family communication about maternal BRCA1/2 genetic testing with minor children, and decisions and outcomes of disclosure.

Introduction

Observational studies suggest that a majority of patients tested for BRCA1/2 mutations who are raising children will disclose their test results to these children (1-5). However, our understanding of the predictors of disclosure to children and its outcomes remains extremely limited. Early evidence suggests that disclosure decisions may be influenced by patient demographic (e.g., child age) and clinical factors (e.g., family history) (2, 5), but decision-making and psychological factors are poorly characterized and impede intervention.

Disclosure has important implications for patients, their partners, and offspring (3, 5, 6). A better understanding of psychological factors associated with the decision to disclose, and patient outcomes of disclosure, could facilitate the development of targeted and tailored decision support interventions to better assist patients in making disclosure choices and improve cancer genetic testing outcomes (6, 7).

Given the scant research in this area, our study sought to investigate the prevalence of patient disclosure of BRCA1/2 genetic test results to children and to identify demographic, clinical, decision-making, and psychological predictors of this outcome. A second objective was to assess patients’ satisfaction with their disclosure choice, ascertaining predictors of higher satisfaction in this important context. These variables were assessed in the context of behavioral decision-making theory (8, 9) and Baum’s model of stress and genetic testing (10).

Patients and Methods

Study Design and Patients

Methods for this prospective, observational study have been described previously (6, 11). Patients were 221 mothers to one or more children age 8-21 years. All patients underwent pretest BRCA1/2 genetic counseling, provided a DNA sample for genetic testing at one of three cancer centers in DC, MA, or NY, and received their cancer genetic test results: no children were genetically tested through this research program. The study sites host well-established hereditary breast/ovarian cancer clinical research programs, and all procedures were approved by the Institutional Review Boards at each site.

Study Procedures

Patients were screened and approached for participation by their cancer genetic counselor at the conclusion of their pretest genetic counseling appointment and after providing a DNA sample. Study eligibility included self-identification as a mother to ≥ 1 child age 8-21 years-old. At enrollment, patients enumerated their children including ages, dates of birth, genders, birth order, and birth relationship (e.g., biological child). For those with > 1 child, a computerized random selection algorithm designated a target child of interest within the study age range to alleviate parental selection, reduce bias, and maintain 1:1 parent-child dyads for statistical analysis (12-14).

Patients completed telephone interviews at baseline, following pretest genetic counseling, and again at follow-up 1-month post-test counseling. The timing of the follow-up was based on prior research indicating that most disclosures to relatives (including children) occur shortly after post-test counseling (5, 15). A modest incentive ($5 gift card) was offered to acknowledge each patient interview completed. In total, 79% of eligible patients consented to participate (n = 262) and 84% of consented patients (n = 221) completed both assessments and were included in our analyses. Compared to patients with incomplete assessments (n = 41), patients included in the analysis were significantly more likely to have a college education (78% vs. 60%, P < 0.001). No other differences were evident based on demographic or clinical characteristics.

Survey Measures

Outcome Variables

Two outcomes were analyzed for this study. First, a dichotomous variable indicating patient self-disclosure of BRCA1/2 test results to the target child, based on a single item with established face validity and reliability (4, 5). Second, satisfaction with the disclosure decision, as measured at follow-up using the 4-item Effective Decision subscale of the Decision Conflict Scale (DCS) (Cronbach α = 0.76) (16). This addressed making an informed choice, consistency of the decision with patient values, and overall satisfaction. Higher scores indicate less decision satisfaction (16).

Demographic and Clinical Information

Patient and child demographics, and information about the patient’s personal and family history of breast/ovarian cancer, were self-reported at baseline. BRCA1/2 genetic test results were obtained from clinical records prior to follow-up.

Disclosure Decision-Making Process

The pros (5-items) and cons (5-items) of patients disclosing BRCA1/2 test results to their child were assessed at baseline and again follow-up (Cronbach’s α > 0.80) (5). All items were specifically worded to reflect this choice. Pros/cons ratios were computed and used for analyses. Decisional conflict surrounding the disclosure choice was measured with a separate 10-item version of the DCS at baseline and follow-up (Cronbach’s α > 0.75) (17). Items captured decision uncertainty, understanding potential pros/cons of decision outcomes, and decision support: higher values indicate greater decisional conflict.

Psychological Distress

The 15-item Impact of Events Scale-Revised (18) and a modified 12-item version of the Brief Symptom Inventory (BSI) (19-21) measured cancer-specific and general psychological distress, respectively, at baseline and follow-up (all Cronbach’s α > 0.80). Higher values correspond to greater distress. Our BSI included items comprising the Anxiety and Depression subscales, with a 4-point Likert scale (“not at all” to “extremely”) that has been used extensively in genetic testing outcomes research (20, 22). Psychological distress observed in our sample was comparable to that reported in other BRCA1/2 testing studies (20).

Statistical Analysis

Descriptive statistics and bivariate tests (χ² tests, t tests) described the sample and identified baseline predictor variables associated with the maternal disclosure outcome at follow-up. Predictors of disclosure at P < 0.10 were then regressed onto the outcome in a multivariable logistic regression model. We used a similar approach to identify predictors associated with post-decision satisfaction (P ≤ .10), applying non-parametric bivariate tests (Wilcoxon rank sum test, Spearman’s ρ) due to the non-normal distribution of the satisfaction variable. Multivariable linear regression then examined predictors of satisfaction with the disclosure decision. To obtain robust estimates, follow-up decision conflict and satisfaction variables were log-transformed (23). As predictors and outcomes were measured on different scales, both unstandardized and standardized coefficients are reported.

A total of 12 patients in our sample (5.4% of study total) were members of the same kindred. Thus, we examined the extent to which study data were correlated within kindreds to determine the need for adjustment due to familial clustering. The intra-class correlation (ρ) for both outcomes approached 0.08, which is smaller than what has previously been reported in kindred studies of behavioral outcomes of BRCA1/2 testing (24). To assess the potential impact of familial clustering, we ran our final regression models as both generalized (PROC GENMOD) and mixed-linear models (PROC MIXED), respectively, accounting for non-independent data. These parameter estimates and interpretations were essentially unchanged. Therefore, we report our findings from the standard logistic and linear models described above.

Results

Participants

Table 1 displays the characteristics of patients and their children at baseline, stratified by child disclosure status. Demographically, minorities comprised 19% of the study total: 9% Black/African American, 4% Hispanic, and 6% multiple other racial/ethnic identifications. The breakdown of genetic test results was 11% true negative (noncarriers), 75% uninformative (no mutation identified in a member of a kindred without a known mutation), and 15% positive (carriers). In all, 62.4% of patients reported disclosing BRCA1/2 test results to their child.

Table 1.

Patient Demographic and Clinical Characteristics by Child Disclosure Status (N = 221)

	All (N = 221)				Disclosed (n = 138, 62.4%)				Not Disclosed (n = 83, 37.6%)
Characteristic	Mean	SD	No.	%	Mean	SD	No.	%	Mean	SD	No.	%	P
Maternal Demographics
Age, years	46.2	6.0			47.4	5.7			44.2	6.1			<.001
Race/Ethnicity													.05
Non-Hispanic White			180	81.4			107	77.5			73	88.0
Non-White			41	18.6			31	22.5			10	12.0
Education													.18
<College			48	21.7			34	24.6			14	16.9
≥College			173	78.3			104	75.4			69	83.1
Marital Status
Married/Living as Married			185	83.7			109	79.0			76	91.6	.01
Unmarried			36	16.3			29	21.0			7	8.4
Household Income													.15
<$75,000/year			43	19.5			31	22.5			12	14.5
≥$ 75,000/year			178	80.5			107	77.5			71	85.5
Maternal Clinical Characteristics
Family Cancer History
≥1 Affected Relative			115	52.0			70	50.7			45	54.2	.62
0 Affected Relatives			106	48.0			68	49.3			38	45.8
Personal Cancer History
Yes			127	57.5			79	57.3			48	57.8	.93
No			94	42.5			59	42.7			35	42.2
BRCA1/2 Carrier Status													.05
True negative/Uninformative			189	85.5			123	89.1			66	79.5
Positive			32	14.5			15	10.9			17	20.5
Child Age													<.001
<13 years			108	48.9			39	28.3			69	83.1
≥13 years			113	51.1			99	71.7			14	16.9
Child Gender													.41
Female			109	49.3			71	51.4			38	45.8
Male			112	50.7			67	48.6			45	54.2
Disclosure Decision-Making
Decisional Balance	2.1	1.5			2.7	1.4			1.1	0.8			<.001
Decisional Conflict	10.2	16.3			9.5	15.8			11.5	17.2			.51
Distress
General Distress	17.0	5.8			16.7	5.5			17.7	6.3			.20
Cancer-Specific Distress	20.9	17.3			19.4	16.8			23.3	17.9			.10

BRCA1/2 Disclosure Decision

Bivariate Results

Bivariate associations with patients’ BRCA1/2 disclosure status are also displayed in Table 1. Disclosing patients were of older age and more likely to be non-white, unmarried, and to have received true negative or uninformative BRCA1/2 test results. Disclosing patients were more likely to do so to teenagers and young adults vs. younger children and, on average, reported that the pros of disclosure outweighed the cons by a factor of nearly 3:1.

Multivariable Results

Results from the logistic regression analysis are displayed in Table 2. The adjusted odds of patients disclosing BRCA1/2 test results to their child were significantly greater among those receiving true negative or uninformative results (Odds Ratio [OR] = 3.11; 95% Confidence Interval [CI] = 1.11 to 8.71; P =0.03) and those whose child was age 13 or older (OR = 5.43; 95% CI = 2.18 to 13.53; P < .001). The adjusted odds of patient disclosure to their child increased significantly as the ratio of pros to cons of disclosure to children increased (OR = 2.40; 95% CI = 1.63 to 3.54; P <.001).

Table 2.

Multivariate Logistic Regression Analysis of Patients' Disclosure to Children at Follow-Up

	Odds Ratio	95% CI	P
Maternal Demographics
Age
<46 years	0.74	0.32, 1.68	.47
≥46 years	Reference
Race
Non-Hispanic White	0.68	0.25, 1.88	.46
Non-White	Reference
Marital Status
Married/Living As Married	0.60	0.20, 1.79	.36
Not Married	Reference
Maternal Clinical Characteristics
BRCA1/2 Carrier Result
Negative/Uninformative	3.11	1.11, 8.71	.03
Positive	Reference
Child Age
≥13 years	5.43	2.18, 13.53	<.001
< 13 years	Reference
Disclosure Decisional Balance	2.40	1.63, 3.54	<.001

Model Wald χ² 6 df = 55.9; P <.001

Hosmer-Lemeshow Goodness of Fit χ² 8 df = 9.5; P = .30

Post-Decision Satisfaction

Bivariate Results

Patients reported modest levels of satisfaction about their disclosure decision at follow-up (M = 5.7, SD = 13.0). Patients receiving positive BRCA1/2 test results (M = 10.5 [SD 16.4]), and those who did not disclose results to their child (M = 10.4 [SD = 18.2]), were less satisfied than those receiving negative or uninformative results (M = 4.8 [SD = 12.1]; z = 2.41; P = .016), and those who disclosed (M = 2.8 [SD = 7.1]; z = 3.26; P = .001). Patients with greater decisional conflict (Spearman’s ρ = 0.39; P < .001) and psychological distress (Spearman’s ρ = 0.15; P = .02) were also less satisfied with their disclosure decision.

Multivariable Results

Results from the linear regression analysis are displayed in Table 3. After adjusting for other model variables, disclosing patients reported significantly greater satisfaction with their disclosure decision compared with patients who did not disclose to their child (Standardized β = −0.27, P < .001). As decisional conflict increased, patients were less satisfied with their disclosure decision (Standardized β = 0.41, P < .001). Less satisfaction with the decision to disclose was further predicted by greater cancer-specific distress, although this finding only approached conventional statistical significance (Standardized β = 0.11, P = .069). While general distress was associated with decision satisfaction in bivariate analyses at follow-up (P < 0.10), it did not significantly predict satisfaction in regression analyses and was removed from the final model. Overall, the final model explained 26% of the outcome’s variance.

Table 3.

Predictors of Patients' Satisfaction with the Decision to Disclose at Follow-Up

	B	SE B	Standardized β	P
Disclosed BRCA1/2 Test Result				<.001
Yes	−0.31	0.07	−0.27
No	Reference
BRCA1/2 Status				.816
Negative/Uninformative	−0.02	0.07	−0.01
Positive	Reference
Decisional Conflict	0.41	0.06	0.41	<.001
Cancer-Specific Distress	0.004	0.002	0.11	.069

Model R² = 0.26

Discussion

This study focused on predictors and outcomes of patient decisions regarding the disclosure of maternal BRCA1/2 genetic test results to their children. Although the current ages of the children in these families largely precluded them from being candidates for BRCA1/2 testing themselves (25), we observed that disclosure was common with 62.4% of children being informed of their mother’s risk status. Disclosure was more likely to occur when patients received either true negative or uninformative BRCA1/2 test results, and when children were age 13 years and older. That patients were more likely to share the ‘good’ news with their child that a risk-conferring mutation in BRCA1/2 was not found upon genetic testing is consistent with other positive parenting practices (11), even though the clinical interpretation of these test results (i.e., true negative, uninformative) differs substantially. In an earlier study, we reported that patients’ anecdotal motivations for disclosure to children centered on promoting the parent-child bond, maintaining family health, and promoting positive child affect (11). Our results underscore the importance of parents taking into account both cancer genetic test results and the age of the child to be informed when making disclosure decisions. The effect of child age was especially salient in our model. Here, patients’ likely heed risk communication messaging strategies advocated by oncologists and health care providers emphasizing that information be shared with potentially at-risk relatives who might benefit from such information, including their offspring (26). Toward that end, it is likely that disclosure to uninformed younger children will eventually take place over time, perhaps when the child is older and he/she is more ready and mature, and with need for the information.

With respect to the decision outcomes, two findings are especially noteworthy. First, patients’ decision to disclose to their child was more likely to occur as the perceived benefits of disclosure increasingly outweighed the risks. As measured in this study, benefits included the child’s right to know the information, that the results conveyed ‘good news’, to alleviate children’s worry, and to promote greater trust and open communication between the parent and child. By contrast, risks included that the child was too young or immature to appreciate the information, disclosure might promote worry in the child, or the significance of the results to the child were uncertain. These complex themes surrounding familial disclosure of cancer genetic test results are encountered in clinical settings, and underscore the importance of oncologists and other health care providers attending to them to improve the outcomes of BRCA1/2 testing (1). Interestingly, the group of children who might sooner and most directly benefit most from the knowledge of their mothers’ familial cancer risk are older adolescent and young adult children of BRCA1/2 mutation carriers. However, mutation carriers were the least likely to inform these offspring. Although it is possible that carrier mothers will eventually inform their children of hereditary cancer risks as these children emerge into young adulthood, studies of cascade testing and second-generation testing among BRCA1/2 mutation carrier families have not followed children longitudinally. Today, we know very little about the long-term outcomes of BRCA1/2 testing as children grow-up in these family environments. Work by van Oostrom and colleagues reports that having a parent with cancer during one’s childhood places the individual at greater risk for psychological distress during genetic testing (27). As cancer genetic testing proliferates, especially among members of affected kindreds (28), it is increasingly important for clinicians to attend to the age at which the prospect of harboring a familial mutation was first recognized in the family, disclosed to the patient, and with what effect.

Second, when we examined patients’ satisfaction with their disclosure decision, we found that satisfaction was lowest among those who did not disclose and those who were more conflicted about their decision. By contrast, satisfaction was highest among disclosing mothers with less conflict. Thus, patients who would like to disclose to their child but do not, and are uncomfortable with their choice, remain in a state of psychological conflict. This combination portends the onset of disrupted parent-child communication surrounding hereditary cancer. If persistent and unabated, it runs counter to clinical practice guidelines promoting open family communication about hereditary risks. Here too, more data are needed about the long-term outcomes of patients’ disclosure decisions and their impact on parent and child preventive health measures and well-being.

Limitations to this work include the predominantly non-Hispanic White patient sample with an above-average income which limits generalizability. Race/ethnic differences in family communication within and across the socioeconomic gradient would be important to study in the future. Also, our project relied on brief, self-report outcome measures and a modified version of the BSI. Standardized, multidimensional/multimodal assessments could lend insight into patients’ family communication processes and help to better characterize observed variations relative to population norms and other studies.

Despite these limitations, this work is important because it permits a fuller understanding of the clinical impact of the commonest form of genetic testing for adult-onset cancer (BRCA1/2 testing) as a cancer control strategy for high risk individuals and their potentially at-risk family members. Our work highlights decisions and decisional outcomes of disclosure to an overlooked subgroup of first-degree relatives--minor children of adult patients--in an more in-depth manner than studied previously. These new findings call for decision support interventions to better the testing process for patients with children. Prior work indicates that concern for children’s (especially adolescents’) future well-being is a salient motivation behind parents’ decisions to participate in cancer genetic testing (4, 29, 30). Genetic information can shape both individual and collective (e.g., familial) identities about the burden of cancer and shared risks of inheritance, its likelihood of intergenerational transmission, and perceptions about the effectiveness of common risk-reduction methods (e.g., screening, nutrition, physical activity, tobacco avoidance) (31). For some young offspring, information learned through a family member’s genetic testing may be empowering and become part of health promotion efforts (32-34). Clinicians and public health specialists working with at-risk families should examine the psychological, medical, and health behaviors of these children over time and develop adjuncts to genetic counseling that improve patients’ decision-making regarding disclosure of their risk status to their children.