Parent of Origin Effects on Family Communication of Risk in BRCA+ Women: A Qualitative Investigation of Human Factors in Cascade Screening

Pathogenic germline variants in Breast Cancer 1/2 (BRCA) genes confer increased cancer risk. Understanding BRCA status/risk can enable family cascade screening and improve cancer outcomes. However, more than half of the families do not communicate family cancer history/BRCA status, and cancer outcomes differ according to parent of origin (i.e., maternally vs. paternally inherited pathogenic variant). We aimed to explore communication patterns around family cancer history/BRCA risk according to parent of origin. We analyzed qualitative interviews (n = 97) using template analysis and employed the Theory of Planned Behavior (TPB) to identify interventions to improve communication. Interviews revealed sub-codes of ‘male stoicism and ‘paternal guilt’ that impede family communication (template code: gender scripting). Conversely, ‘fatherly protection’ and ‘female camaraderie’ promote communication of risk. The template code ‘dysfunctional family communication’ was contextualized by several sub-codes (‘harmful negligence’, ‘intra-family ignorance’ and ‘active withdrawal of support’) emerging from interview data. Sub-codes ‘medical misconceptions’ and ‘medical minimizing’ deepened our understanding of the template code ‘medical biases’. Importantly, sub-codes of ‘informed physicians’ and ‘trust in healthcare’ mitigated bias. Mapping findings to the TPB identified variables to tailor interventions aimed at enhancing family communication of risk and promoting cascade screening. In conclusion, these data provide empirical evidence of the human factors impeding communication of family BRCA risk. Tailored, theory-informed interventions merit consideration for overcoming blocked communication and improving cascade screening uptake.


Introduction
Breast cancer is the most common female cancer diagnosis and approximately 2.1 million women were newly diagnosed with breast cancer in 2018 [1]. Approximately 10% of all breast cancers are inherited and associated with family history [2]. Notably, women harboring pathogenic variants in BRCA1 or BRCA2 have increased risk for developing breast cancer (72% and 69% respectively by age 80) [3]. Thus, detection of BRCA pathogenic variants has significant relevance for medical management as earlier detection and risk reducing strategies (i.e., hormonal treatment, risk-reducing surgery) can improve outcomes. The United States Preventive Services Task Force has recently updated evidence-based recommendations for risk assessment, genetic counseling and genetic testing themes drawn from the literature to produce a coding template followed by a grounded theory approach to identify additional sub-codes emerging from the interview data (i.e., thematic template analysis, see Materials and Methods). We employed the TPB [24] as a guiding framework for understanding family communication of genetic risk. Additionally, we identify targets at the individual, family and health system level for facilitating intrafamilial communication and enabling cascade screening.

Results
A total of 97 BRCA+ women were interviewed for this study. Nearly two-thirds of women (62/97, 64%) had inherited the pathogenic variant from their mother, while 35/97 (36%) had a paternally inherited pathogenic BRCA variant. Demographic characteristics did not differ by parent of origin (Table 1). Participants were overwhelmingly white/Caucasian who were well educated (at least some college) and self-identified as being middle class. The rates of BRCA testing within specified age brackets did not differ according to paternal vs. maternal inheritance (18)(19)(20)(21)(22)(23)(24)(25)  These findings differ from prior reports [6][7][8]14], demonstrating that women harboring maternally inherited BRCA variants have genetic testing earlier than their paternally inherited counterparts do. The discordant findings are likely due to smaller sample size of the present qualitative investigation compared to previous quantitative studies. However, women with paternally inherited pathogenic BRCA variants were more likely to have been diagnosed with cancer compared to maternally inherited counterparts (13/34 vs. 9/62, χ 2 = 6.99, p = 0.008). We then sought to examine these differences using qualitative inquiry. There are three levels providing structure for the qualitative analysis. The broadest category includes "template themes" that serve as central organizing concepts for understanding the research question. Iterative qualitative analysis (termed coding) identifies emergent "sub-codes" that are relevant concepts giving meaning to the template theme. Lastly, "dimensions" are elements that provide context for the sub-codes. Women harboring paternally inherited pathogenic BRCA variants shared stories highlighting the template theme of 'gender scripting' (i.e., gender-specific roles and activities). Iterative coding of interview data identified sub-codes providing further insight into how 'gender scripting' either promoted or inhibited communication of risk within families and 'paternal guilt' respectively ( Figure 1).

Figure 1.
Sub-codes mapping to the template theme 'gender scripting' in paternally inherited pathogenic BRCA variants. Analyzing interviews (n = 35) with women harboring paternally inherited pathogenic BRCA variants identified four sub-codes (small circles) and related dimensions (bulleted) that are linked to the template theme of 'gender scripting'. Two sub-codes facilitated intrafamilial communication of risk (+) while two contributed to blocked communication (−).
For example, the sub-code 'fatherly protection' included dimensions of actively 'seeking out genetic testing' to inform the family and 'doing whatever it takes' to be supportive of their daughter ( Table 2). The sub-code 'female camaraderie' emerged from stories of mothers and aunts being the "keepers" of family history. Such women assumed a "detective" role to identify risk and subsequently took action and shared information with at-risk relatives (Table 2). Conversely, traditional male roles could also inhibit family communication of risk. The sub-code 'male stoicism' included daughter-identified dimensions including 'inexpressiveness', 'denial' (i.e., "not my problem") and 'fear of being vulnerable'. Interestingly, some interviewees noted that female family members taking on the role of "family detective" and "BRCA informant" (i.e., sub-code 'female camaraderie') helped surmount blocked communication resulting from male stoicism. The 'Paternal guilt' sub-code emerged as the negative counterpoint to the 'fatherly protection' sub-code. 'Paternal guilt' was marked by dimensions of 'sadness' and 'remorse' for passing the pathogenic BRCA variant to the daughter. Women with maternally inherited pathogenic BRCA variant also exhibited distinct 'gender scripts' around communication. Specifically, mothers frequently acted as a "guide" for their daughters in relation to BRCA risk. Indeed, mothers often took on the "BRCA informant" role. This active role in communicating risk within families was the counterpoint to general reluctance to discuss BRCA risk among men in paternally inherited families. Interviews revealed three main sub-codes negatively affecting the template theme of 'family dynamics' (Figure 2). Sub-codes emerged from both maternally and paternally inherited BRCA families. The sub-code 'harmful negligence' included dimensions relating to 'lack of urgency' and/or 'fear of reality' that BRCA risk existed in the family (Table 3). Women feeling uncomfortable discussing breasts/ovaries/reproduction with male relatives (i.e., dimension: 'gendered body sensitivities') also emerged as a barrier to communication. Another emergent finding relating to 'family dynamics' was the sub-code 'intra-family ignorance' that prevented the recognition of clinical red flags raising the suspicion of hereditary cancer risk. Familial ignorance included dimensions of 'obscured family history'-wherein families were unaware or did not recognize their family cancer history and risk. Limited genetic literacy was a barrier as family members did not understand that men were able to inherit pathogenic BRCA variants and pass them on to their offspring, effectively rendering males invisible when identifying risk (dimension: 'male invisibility'). While 'harmful negligence' and 'intra-family ignorance' sub-codes are unintentional, the third emergent sub-code reflected deliberate action. 'Active withdrawal of support' represents a conscious decision to pull away from a BRCA+ family member. Associated dimensions include avoidant family coping (i.e., 'family denial'), a dominant father figure ('paternalistic family structure') and refusal of support for the family member affected by BRCA (i.e., 'condemnation/cold shoulder') Notably, we observed the dimension of 'family denial' was much more prominent in interviews of women harboring a paternally inherited pathogenic BRCA variant. Through the eyes of their daughters, we see that fathers often kept familial risk to themselves. Women harboring paternally inherited pathogenic variants frequently described their fathers as reluctant to discuss cancer/BRCA and often chose non-disclosure over facing the perceived stigma of being a BRCA+ man. Such experiences cultivated a culture of silence that delayed genetic testing and was potentially harmful to all at-risk relatives who could benefit from cascade screening (Table 3). Women considered their fathers' 'active withdrawal of support' and 'denial' as a reaction to BRCA stigma and perceived indictment of paternal culpability. Many interviewees also considered that their BRCA+ status and potential mortality was perceived as a threat to family stability. Emergent themes relating to 'family dynamics' highlight both unintentional and intentional barriers to effective intrafamilial communication. Such barriers enable familial cancer risk to go undetected for generations and prevent cascade screening. When BRCA risk remained unknown in families, stories of secrecy, silence, emotional distance and discomfort discussing medical history were often noted in interviews (Table 3). Women also cited geographic distance, socioeconomic differences and disparate lifestyles as reasons contributing to lack of communication regarding BRCA risk. These observations are consistent with previously reported barriers to cascade screening [5].  Active withdrawal of support Participant 035 on her father urging her and the family to 'move on with their lives' and subsequently withdrawing support for her: "I think he became a real jerk about it too. He was just like, just move on . . . move on with your life already. And I think that's cause he wanted to move on with his life like I think he felt really guilty for giving it to me."-She goes on to explain how this resulted in family conflict and her mother subsequently squashing any conversation about BRCA to avoid upsetting her husband and sons.

Template Theme 3: 'Medical Biases'
Interviews revealed sub-codes related to ingrained misconceptions and implicit biases among healthcare professionals regarding gender that facilitate/impede understanding risk imparted by pathogenic BRCA variants. Both 'medical misconceptions' and 'medical minimizing' emerged as sub-codes undermining accurate assessment of BRCA risk. In contrast, other interviews identified factors promoting accurate assessment of familial cancer (BRCA) risk. Women appreciated healthcare professionals who understood that BRCA can be passed via maternal or paternal inheritance (i.e., sub-code: 'informed providers'). Another mitigating factor of 'medical biases' was the sub-code of 'trust in healthcare' (i.e., patient-centered care, healthcare professionals who placed patient concerns at the center of discussions and decisions) ( Figure 3). Notably, quotes drawn from interviews point to a matrix of gender role influences on how some healthcare professionals assess BRCA risk assessment and how some families communicate BRCA risk (Tables 1 and 4).  Cascade screening hinges on intrafamilial communication of BRCA risk. However, family communication is complex and dynamic. We used the TPB [24] to better understand the revelation of BRCA family risk as a key element for cascade screening. Sub-codes were mapped onto the TPB to better understand the interplay of factors influencing family communication around BRCA risk ( Figure 4). Briefly, the TPB posits that experiences and beliefs shape attitudes (i.e., good/bad) towards a particular behavior (i.e., family communication of risk). We considered three sub-codes relating to decreased/ineffective family communication of risk ('paternal guilt', 'harmful negligence', 'intra-family ignorance') as relating to TPB attitudinal factors. In the TPB, subjective norms relate to social/family norms (i.e., whether most people approve or disapprove). Interestingly, sub-codes under this category relate to traditional male roles yet represent opposite sides of the coin so to speak. The sub-code 'male stoicism' (i.e., being a strong male) was associated with limited family communication of risk. Conversely, 'fatherly protection' (safeguarding the family) fostered communication of family risk. The TPB posits perceived behavioral control relates to an individual's sense of agency and self-efficacy for performing a particular behavior. Gender roles represented both inhibiting and promoting factors for family communication. 'Female camaraderie' helped promote BRCA awareness in families. Indeed, female family members often felt "empowered" and "obliged" to communicate risk. Alternatively, family members who were unable to cope with family risk and/or BRCA stigma (i.e., low self-efficacy for communication) often reacted with 'active withdrawal of support'. The TPB posits that beliefs shape attitudes that influence intention which precedes behavior; (B) social and cultural beliefs shape perceived social pressures creating subjective norms that influence intention; (C) control beliefs shape perceived behavioral control (i.e., self-efficacy, perceptions of one's ability to perform the behavior). Sub-codes (bullets) emerging from the two family-related template themes ('gender scripting' and 'family dynamics') were mapped to the TPB to elucidate the matrix of patient and family-related factors that either promote (+) or inhibit (−) communication of risk and subsequent cascade screening.
To identify targets for interventions aimed at enhancing family communication of risk and promoting cascade screening, we combined the TPB mapping exercise with sub-codes relating to the healthcare system (template theme: 'medical biases'). This ecological approach identified individual, family and institutional targets for interventions [35]. Proposed interventions (Table 5) targeting the individual include employing principles of behavioral economics and motivational interviewing.

Sub-Codes Potential Interventions
Fatherly protection (+) Male stoicism (−) • Framing masculine role as the family protector (i.e., being a good father = sharing information to protect the family)

Sub-Codes Potential Interventions
Female camaraderie (+) • Empowering women to be a "BRCA informant" for the family to spread knowledge of risk through the family and highlighting the advantages of early detection and intervention • Genetic counseling to support recognition that genes and inheritance are beyond one's individual control, reframe the focus to recognize that knowledge is powerful for enabling cascade screening, heightened surveillance and early risk-reducing interventions • Use family systems approach to "nudge" family members to rally around affected members

Discussion
Herein we present data from 97 qualitative interviews with BRCA+ women to better understand family communication around BRCA cancer risk that precedes cascade screening. Previous studies have demonstrated differences between family members in reporting maternal and paternal history of cancer respectively [11,12,16]. Additionally, we have previously shown differences in approaches to risk management and psychosocial burden according to parent of origin [14]. Indeed, women with maternally inherited pathogenic BRCA variants more frequently report open family communication, being aware/informed of risk, feeling more empowered and are more likely to exhibit proactive risk management as well as better health and psychosocial outcomes [14]. Using template analysis using themes drawn from existing literature, we sought to consider sex as a variable to parse the role of communication in the divergent parent of origin outcomes. A comprehensive literature review identified three template themes (gender scripting, family dynamics, medical biases) that guided our examination of BRCA parent of origin effects on intrafamilial communication. The emergent sub-codes (and dimensions) in the present study provide a broad picture of facilitators and barriers to discussing BRCA risk in families with important ramifications for cascade screening. Notably, we report a matrix of gender role influences that exist within families and among healthcare professionals.
The literature consistently identifies several universal barriers to effective family communication of risk and cascade screening including poor knowledge/understanding of genetics and heritability, limited communication skills, financial barriers (i.e., cost, insurance coverage), anxiety/depression in probands and/or relatives and geographic barriers to accessing genetic services [5]. Studies have noted the uptake of cascade screening to be lower in male relatives compared to females. However, the reasons for lower uptake of testing among males have yet to be elucidated. This study presents qualitative empirical data providing insights into the human factors and potential mechanisms (including parent of origin) that help explain the observed sexual discordance in cascade screening. Qualitative inquiry is recognized as an essential component of developing complex interventions [22,23], and the present findings can inform tailored interventions for families. Best practices for developing and testing complex interventions include the incorporation of theories/frameworks to guide the process [22,23].
Thus, mapping our findings onto the Theory of Planned Behavior (TPB) contributes to advancing novel, tailored family interventions promoting cancer predisposition cascade genetic testing for BRCA. This theoretical contribution towards developing complex interventions promoting cascade screening is further supported by the demonstrated utility of the TPB in breast cancer and genetic counseling [25][26][27][28][29][30][31][32][33].
Gender scripting is a major theme contributing to parent of origin differences in medical and psychosocial outcomes [14]. Traditional western gender roles consider males as strong, assertive, independent providers and protectors, while females have greater emotional sensitivity, are more sociable and have a greater concern for others [36]. Such gender scripts can have positive benefits for promoting family communication such as 'female camaraderie'-a relative who takes on the role of 'family record-keeper' and 'detective' to emerge as the family "BRCA informant". Similarly, men who identify with the protector role (sub-code: 'fatherly protection') sought out testing and were dedicated to doing "whatever it takes" to help their daughter. Interviews revealed that gender roles and implicit biases often impede open discussion of BRCA risk within families. Conversely, shadow sides of male roles took the form of 'parental guilt' for transmitting the pathogenic variant (i.e., not being a good protector) and 'male stoicism' (e.g., dimensions of 'denial' and 'inexpressiveness'). Gender scripts also contributed to the sub-code of 'intra-family ignorance'. In particular, misperceptions that BRCA status relates only to breast cancer (i.e., a "woman's disease") contributed to 'stigma' and the dimension of 'male invisibility'. Male history was often invisible, thus red flags were not recognized in family history and risk was not communicated within families. Similarly, gender roles created barriers for male-female communication. Specifically, individuals noted family member discomfort with talking about their body with relatives of the opposite sex (dimension: 'gendered body sensitivities'). Emotional responses to BRCA cancer risk contributed to dysfunctional family dynamics demonstrated by reports of 'active withdrawal of support' for the BRCA affected family member. Daughters interpreted male emotional retreat as stemming from denial and fear of parental culpability for passing the pathogenic BRCA variant on to them. Notably, gendered scripting and implicit biases were not limited to family members. Some healthcare professionals hold 'medical misconceptions' (e.g., BRCA can only be inherited from the maternal line) that contribute to 'medical minimizing' (brushing off red flags from family history) ( Figure 3, Table 4). Both misconceptions and minimizing can result in delays in seeking care. Notably, delayed care seeking is particularly evident among women harboring paternally inherited pathogenic BRCA variants [14]. Interviews detailed the way gender scripting played out in families and points to human factors contributing to the poorer outcomes observed in women who inherit pathogenic BRCA variants from their fathers [14]. Women noted that gender scripting negatively influenced intrafamilial communication. Indeed, women with a paternally inherited pathogenic BRCA variant described communication as "blocked" and felt "blindsided" by BRCA and cancer [14].
Hereditary cancer resulting from pathogenic BRCA variants has implications for the entire family. Accordingly, open family communication of BRCA risk cancer can be a catalyst for cascade screening and risk reducing strategies, including aggressive surveillance, hormone treatment and/or surgery. Open family communication has been associated with decreased distress [37]. However, families have variable responses to BRCA status ranging from complete openness to limited disclosure to total secrecy [38]. Moreover, men in at-risk families have lower uptake of BRCA testing [39,40] and express greater difficulty divulging BRCA test results with at-risk relatives [35,39]. The sub-codes we identified within the template theme of 'gender scripting' align with observed gender differences in communication and the spectrum of familial response [35,38,39]. Importantly, greater satisfaction with BRCA testing decision (and less regret) is a predictor of open communication in families [18]. Healthcare professionals report barriers to assisting families in effectively communicating risks. Barriers include family lack of understanding about the importance of sharing genetic information with at-risk relatives, family concerns about relatives' emotional response and complex family dynamics [41]. Indeed, our qualitative interviews of BRCA+ women revealed sub-codes ('harmful negligence', 'intra-family ignorance', 'paternal guilt', 'male stoicism', 'active withdrawal of support') that echo the barriers perceived by healthcare professionals. We and others have proposed guilt and silence as significant roadblocks to open family communication around BRCA status [15,16,38,42]. However, families that are able to overcome such reactions and incorporate positive BRCA status into their family narrative (reflected in sub-codes of 'fatherly protection' and 'female camaraderie') can solidify and strengthen the family identity [35]. Thus, theory-based interventions [34] (i.e., drawing on the Theory of Planned Behavior) that target the individual and family may help reframe the threat posed by BRCA and support families into achieving a new level of family coping and adaptation.
Sub-codes from the template theme 'medical biases' (i.e., 'medical misconceptions', 'medical minimizing') were frustrating for patients and eroded patient confidence in the healthcare system. Such observations echo findings from previous studies demonstrating that healthcare provider biases contribute to delays in diagnosis and treatment for women with paternally inherited pathogenic BRCA variants [8,9,14,43,44]. Lack of training/competencies in genetic healthcare and implicit bias have previously been noted to contribute to poor outcomes [44][45][46]. Importantly, there is increasing attention to the pivotal role healthcare providers play in facilitating intrafamilial communication and subsequent cascade screening [15,[47][48][49]. Accordingly, educating clinicians and implementing the recently updated U.S. Preventive Service Task Force recommendations guidelines on risk assessment, genetic counseling and genetic testing for BRCA-related cancer is a critical step in rebuilding trust [4]. Health system leadership should acknowledge trust as foundational to care delivery by establishing standards, providing training and measuring trust to ensure accountability [50]. Further, adopting more person-centered approaches to care is an essential component to fostering cascade screening. Shared decision-making helps foster high quality health decisions that are both informed and aligned with patient values and preferences [50,51]. High quality decisions are associated with greater satisfaction and less regret. Thus, more person-centered approaches to care may have indirect positive effects on family communication, thereby facilitating cascade screening [5,18].
Mapping findings to the TPB identified variables to tailor interventions aimed at enhancing family communication of risk and promoting cascade screening. Approaches (Table 5) would aim to reframe traditional male gender scripts away from 'male stoicism' to a more adaptive "protector" role wherein being a good man/father is about protecting the family and communicating risk. Men may be reluctant to discuss health and family history, yet for many, sports appears to be an easy and accessible topic of male discussion. Each October since 2009, the National Football League has partnered with the American Cancer Society for the "Crucial Catch" campaign to raise awareness of breast cancer screening, particularly for women over 40 years of age [52]. Changing culture (and overcoming traditional societal gender roles) is a massive undertaking, yet change on an individual level may seem more attainable. In light of findings from the current study and others, perhaps a more successful approach for enhancing cancer screening would be to flip the script. In other words, use the "Crucial Catch" campaign to nudge men to consider their family history of cancer (both maternal and paternal) and share that information with at-risk relatives; thereby embracing the traditional western male role as a provider and protector. Envisioned interventions at the family level could take the form of similar counseling approaches aimed at empowering individuals to assume a role of the family "BRCA informant" to raise family awareness and underscore the importance of cascade screening for early detection, aggressive surveillance and risk-reducing interventions (i.e., hormonal therapies and/or surgery) [53]. The primary focus at the health system level aims to improve genomic healthcare competencies and remove implicit biases by adopting the recently updated U.S. Preventive Service Task Force recommendations for risk assessment, genetic counseling and genetic testing for BRCA-related cancer [4]. Such a systems approach (i.e., individual, family, health systems) may be useful as multi-component interventions may be more effective than simply targeting one aspect (i.e., individual, family or institution).
This study has several limitations. First, it is worthwhile to note that we interviewed BRCA+ women and observe comments about parental/family behavior though the eyes of the daughter; we did not interview mothers and fathers directly. Second, we cannot assure that findings (particularly regarding gender roles/scripts) are globally transferable due to cultural differences. However, international studies report results that mirror our findings, underscoring a strong desire among most men to keep genetic information private [18,54]. Second, our sample was rather homogeneous. Studies including more diverse patients are needed for generalizability. Third, our recruitment strategy (i.e., online) could have introduced selection bias, as internet access is not universal. Patients frequenting patient support organizations cannot be assumed to be representative of the broader patient population. Similarly, in-depth interview data may not fully represent the entire spectrum of patient experiences. However, our sample size (n = 97) is very robust for qualitative inquiry and we can be confident that data saturation was reached. The sample size combined with the iterative approach to data analysis help support the validity of our findings.

Materials and Methods
The Boston College IRB approved this qualitative research study (protocol #16.109.01) and all participants provided opt-in electronic informed consent prior to participation. Findings are reported according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE).

Participants and Procedures
A purposive sample was recruited for this study. Women who had tested positive for pathogenic BRCA variants were recruited via social media (i.e., Facebook, Twitter) and several online patient-oriented breast cancer sites (Bright Pink, Facing Our Risk of Cancer Empowered [FORCE], National breast Cancer Coalition) (dates: January 2013-September 2016) [55]. Following informed consent, participants (n = 97) provided information on sociodemographics, family and personal medical history including genetic counseling and genetic testing experiences. A single study investigator (SHB) conducted all 97 interviews. In-depth telephone interviews (1-1.5 h.) were used to capture women's experiences being BRCA+. The investigator started each interview by prompting each participant "to share your BRCA story" and listened deeply. Additional questions elicited personal and family medical history-including experiences with genetic counseling, genetic testing and probing family communication patterns. Interviews were audio-recorded and transcribed verbatim. Field notes were recorded for each interview. All participants were given the option to review their transcribed interview to edit and clarify responses. No participants chose to review their transcript.

Analysis
Demographic and health history characteristics were compared between groups according to parent of origin (i.e., maternal vs paternal inheritance) using Chi-squared or Fisher's exact tests as appropriate. To compare age at genetic testing, maternal and paternal inheritance groups were compared according to age range at time of genetic testing (14, 18-25, 26-30, 31-35, 36-40, 41-50, 51-60, and 61-70 years old). Interview transcripts were analyzed using template analysis [56][57][58]. In brief, this approach to qualitative analysis uses a priori coding template (termed "themes") from the research literature. For this study, template themes were drawn from a comprehensive review of existing literature related to hereditary breast and ovarian cancer, and more specifically, parent of origin (i.e., maternal vs. paternal) inheritance of a pathogenic BRCA variant. A particular strength of template analysis is that it follows a structured top-down approach meaning that the existing literature guides the analysis (i.e., template themes for analyzing the qualitative data). A review of the literature published over the past 10-years identified three template themes (gender scripting, family dynamics, and medical bias). Template analysis methodology allows for the modification of the initial template themes with the addition of sub-themes and dimensions during a grounded theory analysis of qualitative data. A grounded theory analysis consists of reading each interview and doing line-by-line coding. A detailed interview memo is created that includes codes with respective line numbers. Two investigators (B.F., S.R.) independently coded the qualitative data and created interview memos. During the analysis process, emergent analytical themes are identified and tested against subsequent interviews. Three investigators (S.H.-B., B.F., S.R.) discussed emergent themes arising from the iterative coding of interview transcripts. All investigators (A.A.D., S.H.-B., B.F., S.R.) agreed to the final coding structure. This iterative coding process allows for a set of analytical categories to emerge as factors clarifying our understanding of the lived experiences of women harboring pathogenic BRCA variants. Using a grounded theory approach [59], we derived sub-codes and contributing dimensions corresponding to the a priori template themes. Through the iterative process, data were grouped into sub-codes (representing new analytical ideas) and dimensions (providing additional context and nuance) of the sub-codes that were deductively added to the initial template themes.

Theoretical Framework
We use the Theory of Planned Behavior (TPB) [24] as a guiding theoretical framework for interpreting qualitative findings (i.e., sub-codes, dimensions) around family communication preceding subsequent cascade screening. The central premise of the TPB is that intention precedes action. Intentions may be shaped by attitudes (perceptions of good/bad), subjective norms (expectations of family, friends or healthcare professionals) and perceived control (perceived agency and view that the action is up to the individual). The TPB also posits that attitudes, subjective norms and perceived control are influenced by beliefs/values as well as past experiences [24]. Additionally, we employed an ecological perspective to identify targets for improving care at the individual, familial, and healthcare system levels.

Conclusions
In summary, qualitative interviews with 97 women identify a matrix of parent of origin and gender role influences on family communication of BRCA risk influencing cascade screening. Codes related to blocked intrafamilial communication and medical biases contribute to diminished family BRCA awareness and communication of risk. Interestingly, normative beliefs related to roles and gender scripting can pose barriers to communication of BRCA risk (i.e., male stoicism and paternal guilt) and contribute to daughters harboring paternally-inherited pathogenic BRCA variants feeling "blindsided" by cancer. Gender scripts also limit cascade screening efforts, thereby denying at-risk relatives earlier detection and potentially life-saving intervention. Conversely, gendered scripting can also facilitate family communication (i.e., fatherly protection). Based on findings from qualitative interviews, we propose interventions guided by the Theory of Planned Behavior that attend to human factors influencing intrafamilial communication of BRCA risk and subsequent uptake of cascade screening.