Outcomes of support groups for carriers of BRCA 1/2 pathogenic variants and their relatives: a systematic review.

People tested positive for BRCA1/2 face an increased risk of cancer; to help them cope with the genetic information received, support to BRCA1/2 families should be continued after testing. Nonetheless how such support should be provided has not been established yet. As a potentially valuable option is represented by support groups, the aim of this systematic review was to assess studies exploring the outcomes of support groups for BRCA1/2 carriers. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021238416). Peer-reviewed papers published between January 1995 and February 2021 were searched for, using four databases. Among 1586 records identified, 34 papers were reviewed in full-text and eleven were included in the qualitative synthesis of the results. Three themes emerged as major focuses of support groups: risk management decisions, family dynamics and risk communication, and psychosocial functioning. Our findings show that support groups proved helpful in supporting women's decision-making on risk-reducing options. Moreover, during those interventions, BRCA1/2 carriers had the opportunity to share thoughts and feelings, and felt that mutual support through interacting with other mutation carriers help them release the emotional pressure. However, no significant impact was reported in improving family communication. Overall, a high level of satisfaction and perceived helpfulness was reported for support group. The findings suggest that support groups represent a valuable tool for improving BRCA1/2 families care.

Sudden shift to remote genetic counseling during the COVID-19 pandemic: Experiences of genetics professionals in Italy.

The 2020 COVID-19 pandemic has rendered in-person provision of genetic counseling impossible for prolonged periods in many countries, mandating a sudden shift to remote delivery. We used qualitative thematic analysis to explore Italian genetics professionals' experience with remote genetic counseling. Fourteen group and four individual interviews were conducted after participants had delivered one or more remote sessions via videoconference or on the telephone. Data were coded and grouped under themes. Three main themes were identified as follows: (a) technical and logistical issues, (b) communication issues, and (c) clinical content and outcome of the session. The participants acknowledged that not having to travel to the clinic saves consultands time and expense. They also highlighted that not sharing a physical space with consultands and having to rely on technology can negatively impact on effective communication, building trusting relationships, and performing accurate psychosocial assessments. Regarding the clinical content of sessions, remote genetic counseling was perceived to favor greater focus and succinct, to the point communication. However, participants also felt uncomfortable not being able to use visual aids to support the explanation of complex concepts. Moreover, demographics and the socio-cultural status of consultands emerged as factors influencing the outcome of remote genetic counseling sessions. Finally, participants reported feeling that more experience with this novel approach would improve their confidence and their ability to adapt their counseling skills as appropriate. Based on these findings, we suggest that effective, equitable provision of remote genetic counseling will require an infrastructure that is able to support video counseling, sharing of clinical documents and visual aids, and connect with a wide range of devices. Moreover, the structure of sessions should be tailored to the specific requirements of remote genetic counseling and suitable training efforts should be promoted to enhance professionals' communication skills.

Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing.

Exome/genome sequencing (ES/GS) is increasingly becoming routine in clinical genetic diagnosis, yet issues regarding how to disclose and manage secondary findings (SFs) remain to be addressed, and limited evidence is available on patients' preferences. We carried out semi-structured interviews with 307 individuals undergoing clinical genetic testing to explore their preferences for return of SFs in the hypothetical scenario that their test would be performed using ES/GS. Participants were 254 females (82.7%) and 53 males (17.3%), aged 18-86 years; 73.9% (81.1% of those with lower education levels) reported no prior knowledge of ES/GS. Prior knowledge of ES/GS was more common among patients tested for Mendelian conditions (34.5%), compared to those undergoing cancer genetic testing (22.3%) or carrier screening (7.4%). Despite this reported lack of knowledge, most participants (213, 69.6%) stated they would prefer to be informed of all possible results. Reasons in favor of disclosure included wanting to be aware of any risks (168; 83.6%) and to help relatives (23; 11.4%), but also hope that preventive measures might become available in the future (10, 5%). Conversely, potential negative impact on quality of life was the commonest motivation against disclosure. Among 179 participants seen for cancer genetic counseling who were interviewed again after test disclosure, 81.9% had not heard about ES/GS in the meantime; however, the proportion of participants opting for disclosure of any variants was lower (116; 64.8%), with 36 (20.1%) changing opinion compared to the first interview. Based on these findings, we conclude that genetic counseling for ES/GS should involve enhanced education and decision-making support to enable informed consent to SFs disclosure.

Intrafamilial communication of hereditary breast and ovarian cancer genetic information in Italian women: towards a personalised approach.

Genomic testing expansion is accompanied by an increasing need for genetic counselling and intrafamilial communication. Genetic counselling can play an important role in facilitating intrafamilial communication and relationships. We conducted a cross-sectional, multicenter study including 252 Italian women, using a questionnaire divided in two sections, the first one to be filled after the pre-test counselling and the second after receiving BRCA test results. We assessed the factors influencing intrafamilial disclosure of genetic information for hereditary breast and ovarian cancer, family members with whom probands are more prone to share genetic information, and the perceived understanding of information received by counselees during genetic counselling. Women were accompanied to the counselling more often by their husband/partner. Among those with a positive BRCA test result, 49% intended to communicate it to their offspring and 27% to their husband/partner. Younger women, those living with their husband/partner, and those who described family communication as open/profound and spontaneous/sincere had a higher probability of being accompanied during genetic counselling and discuss about it with relatives. Spontaneous/sincere or open/profound family communication and joyful/happy familial relationships were associated with the decision to undergo genetic testing as a responsibility towards relatives. Women had a good understanding of counselling contents (mean score 9.27 in a scale 1-10). Genetic counselling providers should consider that genetic information disclosure does not depend only on the clarity of the information provided, but also on pre-existing intrafamilial communication and relationships, family structure and marital status, indicating the need for a personalised approach accounting for these factors.

Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?

Background: Detection of variants of uncertain significance (VUSs) in BRCA1 and BRCA2 genes poses relevant challenges for counseling and managing patients. VUS carriers should be managed similarly to probands with no BRCA1/2 variants detected, and predictive genetic testing in relatives is discouraged. However, miscomprehension of VUSs is common and can lead to inaccurate risk perception and biased decisions about prophylactic surgery. Therefore, efforts are needed to improve VUS evaluation and communication at an individual level. Aims: We aimed at investigating whether cosegregation analysis, integrated with a careful review of available functional data and in silico predictions, may improve VUSs interpretation and counseling in individual families. Methods: Patients with Breast Cancer (BC) and/or Ovarian Cancer (OC) fulfilling established criteria were offered genetic counseling and BRCA1/2 testing; VUSs identified in index cases were checked in other relatives affected by BC/OC whenever possible. As an alternative, if BC/OC clustered only in one branch of the family, the parental origin of the VUS was investigated. Public prediction tools and databases were used to collect additional information on the variants analyzed. Results: Out of 1045 patients undergoing BRCA1/2 testing in the period October 2011-April 2018, 66 (6.3%) carried class 3 VUSs. Cosegregation analysis was performed for 13 VUSs in 11 kindreds. Seven VUSs (53.8%) did not cosegregate with breast/ovarian cancer in the family, which provided evidence against their role in cancer clustering in those families. Among the 6 cosegregating VUSs, for two (BRCA1 c.5152+2T>G and BRCA2 c.7975A>G) additional evidence exists from databases and in silico tools supporting their pathogenicity, which reinforces the hypothesis they may have had a predisposing effect in respective families. For the remaining four VUSs (31%), cosegregation analysis failed to provide relevant information. Conclusion: Our findings suggest that cosegregation analysis in a clinical context may be helpful to improve test result interpretation in the specific family and, therefore, should be offered whenever possible. Besides, obtaining and sharing cosegregation data helps gathering evidence that may eventually contribute to VUS classification.