1 INTRODUCTION

The prevalence of BRCA1/2 pathogenic variants is estimated at about 1:300 in the general population (Antoniou et al., 2000; Bahar et al., 2001). In the Ashkenazi Jewish population, this prevalence was estimated at 1:40 by previous studies, but more recent large-scale, unbiased screening has shown that the prevalence is closer to 1:100 (Grinberg et al., 2023). Traditionally, oncogenetic counseling and testing for BRCA1/2 variants is initiated when a qualifying personal or family history of cancer is present. In such cases, healthcare practitioners typically refer the patients to formal in-person pre-test genetic counseling, during which a clinical geneticist or a genetic counselor thoroughly assesses patients' medical and family history and explains the aims and consequences of genetic testing. In case of an abnormal result, the patients are usually invited via phone for a follow-up in-person genetic counseling session, while in some cases, the results are communicated solely over the phone. This conventional model is a time-consuming process, constrained by the availability of adequately trained providers. In addition, a significant proportion of carriers can be missed when evaluated based on family history criteria (Gabai-Kapara et al., 2014; Levy-Lahad et al., 1997). Thus, population screening model of healthy individuals for common BRCA variants has been studied in several countries (Greenberg et al., 2023; Morgan et al., 2022).

In 2020, a nationwide screening program was introduced in Israel, offering testing for the common BRCA1/2 variants (BRCA1 c.68_69delAG, BRCA1 c.5266dupC, and BRCA2 c.5946delT) to all females of complete or partial Ashkenazi Jewish origin above the age of 25 years (Greenberg et al., 2023). Under this new program, formal in-person pre-test genetic counseling is not a prerequisite for testing. Instead, women of Ashkenazi origin are referred to blood testing, where they receive brief information about the genetic testing either from a dedicated nurse or a phlebotomist. Women with a personal or familiar history of cancer are referred to a formal genetic counseling. Normal test results are usually communicated to the patients via phone/web notice, while abnormal results trigger further telephone or in-person genetic counseling by a clinical geneticist or a genetic counselor.

Population screening tests for actionable genes in healthy populations are an evolving and increasingly utilized approach in genomic medicine, especially in broader populations without a personal or familial history of cancer. Therefore, identifying weak points and continually learning throughout the process are crucial in setting the standard of care in medical screening. The aims of this research were (1) to evaluate the perceived quality of pre- and post-test explanations, and (2) to compare these outcomes between two cohorts: female BRCA1/2 carriers who underwent genetic testing as part of population screening, vs. those who performed the genetic testing following formal genetic counseling.

2 METHODS

This study employed a cross-sectional, observational design using an anonymous web-based questionnaire. The cross-sectional approach was chosen to capture a snapshot of experiences and perceptions among female BRCA1/2 carriers at a specific point in time, allowing for comparison between those identified through population screening and those diagnosed following formal pre-test genetic counseling.

This web survey was based on the principles of Checklist for Reporting Results of Internet E-Surveys (CHERRIES) (Eysenbach, 2004) as well as the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines (Cuschieri, 2019). As no validated tools exist on the examined subject, the questionnaire was generated for this specific study, developed in a collaboration of a Ministry of Health and managers of “Good genes – a support and information association for BRCA carriers”, based on their experiences and relevant updated literature. “Good Genes” is an Israeli non-profit organization dedicated to support women who carry BRCA1 and BRCA2 disease-causing variants. The organization offers educational resources and provides emotional and psychological support through group and individual sessions, workshops, and lectures. The women register into the community voluntarily following the genetic diagnosis.

The introductory section of the survey elucidated the study's overarching objective, which was to assess the healthcare experiences of females aged 18 years and older carrying the BRCA1/2 disease-causing variants. The anonymity of the survey was emphasized to encourage honest responses and reduce social desirability bias. As such, BRCA carrier status was not confirmed by genetic test report. The questionnaire was structured into three primary sections. The first section assessed the demographic and medical information, encompassing age at the time of BRCA carrier diagnosis, as well as personal and family cancer history. The second section was focused on the evaluation of the process leading up to the BRCA testing. This included a question whether the positive diagnosis arose following formal genetic counseling (prompted by personal or familial cancer history) vs. genetic screening based on Ashkenazi ancestry, or occurred through other circumstances. Furthermore, this section included Likert scale questions evaluating the perceived quality of the pre-testing explanation and various aspects related to the delivery of test results, encompassing their perceived quality, timing, and mode of delivery (e.g., phone, face-to-face explanation, or other). The original Likert scale responses ranged from 1 to 5, with 1 representing “strongly disagree” and 5 representing “strongly agree.” It also assessed the level of stress experienced after receiving a positive genetic result and included open-ended questions soliciting suggestions for improving the clarity of explanations. The third section of the questionnaire was designed to evaluate the quality of recommended medical follow-up, with an in-depth analysis slated for a separate study. Open-ended responses were meticulously and independently categorized by two investigators (LS and MI) using an inductive approach. The questionnaire was administered in Hebrew, and a translated version can be found in Supplementary Document 1. Given that the questionnaire was voluntary and anonymous, it was considered exempt from the need for institutional review board approval.

The survey link was disseminated during January to March 2023 through the “Good genes” association's Facebook page, which boasts approximately 2000 followers. Since there was no prior data available for calculating the sample size, an estimated minimum of 384 participants was considered necessary (Gill & Johnson, 2010). The sole inclusion criterion for the current study was female BRCA1/2 carriers aged 18 or older. BRCA carrier status was self-reported, without no clinical confirmation. Only female participants were included since BRCA screening in Israel is offered only to women of Ashkenazi origin. Key outcome variables were dissatisfaction with the perceived quality of pre-test and post-test explanations. To facilitate analysis and interpretation, the Likert scale responses of 1–3 were considered as dissatisfactory, while stress levels of 4–5 were considered as high. Additional outcomes included dissatisfaction with the mode and timing of result delivery, as well as the associated stress levels.

Following the analysis of the overall cohort, a comparison of sociodemographic characteristics as well as primary and secondary outcomes was performed between two distinct groups: women who underwent genetic testing following population screening (the screening group) vs. formal pre-test genetic counseling (the genetic counseling group). Our primary hypotheses were that patients diagnosed through population screening will report higher dissatisfaction with pre-test explanations compared to those diagnosed following formal genetic counseling; and that the mode and timing of result delivery, as well as the quality of post-test explanations, will be perceived as suboptimal more frequently by participants diagnosed through population screening. Categorical data were presented as numbers (percentages) and compared using Fisher's exact test. Continuous variables were displayed by means ± standard deviations and compared using student's t test. To control for potential confounding variables, we conducted a multivariate logistic regression analysis with dissatisfaction as the dependent variable and group type (screening vs. counseling), timing, and mode as independent variables. p value of <0.05 was considered as statistically significant.

3 RESULTS

The overall study cohort consisted of 554 participants, with a mean age of 51.6 ± 10.1 years, and mean age of positive BRCA diagnosis of 42.3 ± 9.6 years. Among the cohort, 88.1% reported Ashkenazi Jewish heritage, and 51.3% resided in the central region of the country. Additionally, 30.3% reported a personal history of cancer, while 89.2% had a family history of cancer. Dissatisfaction with the pre-test explanation regarding BRCA genetic testing was noted by 31.0% of participants. Table 1 summarizes the participants' recommendations for enhancing the explanation, with the primary suggestion being the provision of more comprehensive information for improved understanding (38.7%), particularly about the implications of a positive test result (30.6%).

Dissatisfaction with post-test explanation was noted by 37.4% of the respondents. Among the 73 women who provided insights into the reasons for this, 35.6% mentioned that the explanation lacked sufficient detail, 31.5% expressed difficulty in comprehending all the details, and 32.9% noted that the experience was excessively stressful. Inappropriate timing for result delivery was reported by 44.7% of participants. Among the 208 women who provided responses to an open-ended question explaining the reasons behind this, 32.1% mentioned they were at their workplace when receiving the results, 10.7% were with their family, 6.2% were driving, 3.1% were undergoing cancer treatments, 2.8% were alone, 1.7% were on public transportation, and 0.7% were in a supermarket. Of the 525 women who answered the question about the mode of delivery of the positive BRCA results, 95 (18.1%) received the results via phone (13.3%) or postal/electronic letter (4.8%), while the remaining 81.9% received post-test explanation through genetic counseling. It is noteworthy that 41.2% of the participants considered the mode of result delivery to be suboptimal. Compared to women who received the results via phone or letter, women who received formal post-test genetic counseling showed lower levels of dissatisfaction with the explanation (55.1% vs. 33.0%, respectively, p = <0.0001), and lower levels of dissatisfaction with the timing (66.7% vs. 38.8%, p = <0.0001) and with the mode of the delivery of the results (66.0% vs. 34.4%, p < 0.0001); however, the post-delivery stress levels did not differ between these women (67.3% in both cohorts, p = 1). Both poor timing (χ² = 140.76, p < 0.001) and poor mode of delivery (χ² = 84.77, p < 0.001) were strongly associated with patient dissatisfaction. Of note, 15.9% stated there might not be an optimal timing and setting for the communication of such significant results. Table 1 outlines suggestions for enhancing the delivery method, providing recommendations for improvement.

Of the examined study cohort, 110 respondents who received the positive BRCA diagnosis through population screening, while 444 individuals were diagnosed following formal genetic counseling. A comparative analysis of the demographic and other relevant characteristics of these two groups can be found in Table 2. Notably, women in the screening group exhibited a later age of BRCA diagnosis, and, as anticipated, a higher prevalence of Ashkenazi Jewish ancestry and lower rates of personal and familial cancer history. In the screening group, 21.5% of the women reported that the results were communicated by phone, letter, or online notice, compared to 17.2% in the counseling group, a non-statistically significant difference.

Table 3 provides an overview of the characteristics related to pre-test explanation and result delivery. Notably, a significantly greater proportion of respondents in the screening group reported suboptimal pre-test explanations when compared to the genetic counseling group (45.5% vs. 27.4%, p = 0.0005). Furthermore, the population screening cohort exhibited higher rates of suboptimal post-test explanations, encompassing the mode, the timing, and the perceived quality of the explanation. Heightened incidence of increased stress associated with the delivery of the results (scored 4–5 on the Likert scale) was observed in this cohort. A logistic regression model controlling for timing and mode of delivery showed that both timing (β = 0.46, p < 0.001) and mode of delivery (β = 0.39, p < 0.001) remained significant predictors of dissatisfaction of post-test counseling, while the type of service (pre-test screening vs. counseling) did not significantly affect dissatisfaction (β = −0.19, p = 0.56).

4 DISCUSSION

The results of our study shed light on several issues of dissatisfaction and shortcomings in pre- and post-genetic testing explanations. These findings point to a crucial need for improvements in the process of pre-test explanation and delivering genetic test results to patients at risk of carrying BRCA disease-causing variants.

First, a significant portion of the respondents expressed dissatisfaction with the pre-test explanations, mainly pointing to the limited nature of the explanations. This indicates a necessity for more comprehensive and detailed explanations, emphasizing the potential consequences of receiving an abnormal result, such as the implications for close monitoring, available surgical options, the associated stress, and the impact on family members. In addition, adjunctive methods such as videos, pamphlets, dedicated websites, and specialized information centers were suggested, and may be used to facilitate pre-test explanations. For instance, in a BRCAsearch prospective Swedish study, high patient satisfaction was shown with delivering the pre-test information by a standardized invitation letter (Nilsson et al., 2019). Additional 2022 study of 331 Ashkenazi Jewish participants shown that more than 85% of participants preferred remote (telephone, print, or web-based) genetic education rather than traditional genetic counseling (Hardy et al., 2022). These percents can differ in women diagnosed as BRCA carriers, such as those included in our study, and additional studies should focus on this specific population. Higher rates of dissatisfaction with the pre-test explanations were noted in respondents undergoing genetic testing in the scope of population screening, vs. those following genetic counseling. This finding might be explained by the practice that pre-test explanations within the realm of population screening are typically conducted within a constrained time frame and not necessarily by genetic counselors. This underscores the imperative for additional education for personnel responsible for conveying such explanations.

Our study also revealed substantial areas for improvement in delivering positive results. The women noted that explanations were often insufficiently detailed, not easily comprehensible, and caused additional stress. Unsurprisingly, greater dissatisfaction was reported among women who received abnormal results via phone or letter, compared to those who received a detailed explanation through counseling. In Israel, it is standard practice to deliver such results through counseling, so it is concerning that 18% of the women indicated they did not receive formal counseling. While this may be related to recall bias, it remains critical to ensure that abnormal results, which are highly stressful and potentially life-changing, are accompanied by proper counseling. Given that dissatisfaction with the mode of result delivery significantly impacted overall satisfaction, it is essential that results are consistently delivered with thorough explanations.

As for timing, the results demonstrated that abnormal results were delivered in various settings, including while driving, on public transportation, at work, and even during routine grocery shopping. Since our findings show that timing independently affects satisfaction with the explanation of the result delivery, it is crucial to establish a more appropriate and regulated approach to result communication.

Based on the insights gained from this study, several conclusions can be drawn for improving the process of positive result delivery. First, in cases where results are delivered over phone, it is of paramount importance to ensure appropriate timing and availability of the patient right at the outset of the conversation. If the proposed time is inconvenient for the patient, there should be flexibility to reschedule the discussion. Another suggestion is a preliminary inquiry with the patients, at the time of obtaining informed consent prior to genetic testing, about their preferences regarding the timing of result delivery, although this solution requires significant systemic evaluations and adjustments. Furthermore, a preliminary inquiry about the preferred method of result delivery might constitute another improvement, suggesting options such as a phone call only, a brief phone call followed by genetic counseling, or, for instance, an invitation by a secretary or a prerecorded message to genetic counseling without disclosing the test result. Additional approaches to improve the current practice can include establishment of a dedicated professional website where the women can access all relevant information for BRCA carriers, detailed brochures summarizing the recommended surveillance tests, as well as continuous emotional support.

It is important to acknowledge the limitations of this research. The study relied on anonymous surveys, methodology subjected to selection and recall bias. Specifically, the BRCA mutation status was not confirmed by genetic test report, and the mode of delivery of the genetic testing was completely self-reported. While the distinction between screening and conventional genetic counseling was based on patient self-report, which may be subject to recall bias as seen in other studies (Wing et al., 2021), we believe this risk is mitigated in our population due to the clear and widely recognized nature of BRCA screening programs in Israel. Additional characteristics of the respondents could be of interest, such as level of Hebrew fluency, education, socioeconomic status, as well as the time between the diagnosis and undertaking the survey. While this study provides valuable insights into the experiences of BRCA1/2 carriers in Israel, particularly those of Ashkenazi Jewish descent, the generalizability of these results should be considered carefully. The findings may be most applicable to healthcare systems implementing or considering population-based BRCA1/2 screening programs, especially in populations with a high prevalence of BRCA1/2 disease-causing variants. The experiences and preferences reported by participants may vary in different cultural, social, or healthcare contexts. Future studies in diverse populations and healthcare systems would be beneficial to confirm the wider applicability of these findings and to identify any context-specific considerations in the genetic testing process.

In conclusion, this research offers valuable insights into the experiences and needs of female BRCA1/2 carriers regarding pre- and post-genetic testing explanations. The findings underscore the importance of improving the clarity, timing, and delivery methods of genetic test results. By addressing these shortcomings and considering the specific preferences of each patient, healthcare providers can better support and guide women facing these challenging decisions.

AUTHOR CONTRIBUTIONS

All authors contributed to conception and design. Lena Sagi-Dain and Moran Echar contributed to data collection. All authors contributed to analysis and interpretation of data. Lena Sagi-Dain and Rotem Greenberg contributed to drafting the article. Amihood Singer and Moran Echar contributed to revising the article. All authors contributed to providing intellectual content of critical importance to the work described and final approval of the version to be published.

FUNDING INFORMATION

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

CONFLICT OF INTEREST STATEMENT

The authors have no relevant financial or non-financial interests to disclose.

ETHICS APPROVAL

The study was considered exempt from the need for institutional review board approval, following consultation with the Helsinki Committee at Carmel Medical Center.