Liliana Varesco

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.

Implementing NGS-based BRCA tumour tissue testing in FFPE ovarian carcinoma specimens: hints from a real-life experience within the framework of expert recommendations

Aims Next Generation Sequencing (NGS)-based BRCA tumour tissue testing poses several challenges. As a first step of its implementation within a regional health service network, an in-house validation study was compared with published recommendations. Methods Epithelial ovarian cancer (EOC) formalin-fixed paraffin-embedded specimens stored in the archives of the eight regional pathology units were selected from a consecutive series of patients with known BRCA germline status. Two expert pathologists evaluated tumour cell content for manual macrodissection. DNA extraction, library preparation and NGS analyses were performed blinded to the germinal status. Parameters used in the study were confronted with guidelines for the validation of NGS-based oncology panels and for BRCA tumour tissue testing. Results NGS analyses were successful in 66 of 67 EOC specimens, with good quality metrics and high reproducibility among different runs. In all, 19 BRCA pathogenic variants were identified: 12 were germline and 7 were somatic. A 100% concordance with blood tests was detected for germline variants. A BRCA1 variant showed a controversial classification. In different areas of two early stage EOCs showing somatic variants, intratumour heterogeneity not relevant for test results (variant allele frequency >5%) was observed. Compared with expert recommendations, main limitations of the study were absence of controls with known somatic BRCA status and exclusion from the validation of BRCA copy number variations (CNV). Conclusions A close collaboration between pathology and genetics units provides advantages in the implementation of BRCA tumour tissue testing. The development of tools for designing and interpreting complex testing in-house validation could improve process quality.

Identification of women at risk of hereditary breast–ovarian cancer among participants in a population-based breast cancer screening

Women attending mammography screening may benefit from family history (FH) assessment for the identification of Hereditary Breast Ovarian Cancer (HBOC). Few studies explored the efficacy of tailored educational interventions in driving the attention on FH-associated risk among these women. To compare the efficacy of two educational tools in increasing attention towards FH, 6.802 women with a negative mammography were randomized to receive a note on FH of breast/ovarian cancer (letter A, n = 3.402) or a note with details on possible implication of FH patterns (letter B, n = 3.200). Upon women's request, a brief questionnaire was administered on phone at the Screening Unit (S.U.) to select those eligible for an in-depth FH evaluation at the Genetic Unit (G.U.). Each affected relative was scored 1-3 according to type of cancer, age at diagnosis, gender, position in the family tree. In all, 401 women contacted the S.U.: 244 (6.6%) in group A and 177 (5.2%) in group B (adjOR 1.27; 95%CI 1.03-1.56). FH scored ≥ 3 for 164 women: 177 (47.5%) in group B and 224 (35.7%) in group A, (adjOR 1.59, 95%CI 1.06-2.38). The G.U. traced and interviewed 148 women, 65 (43.9%) were offered an in-person consultation: 38 attended and 30 were eligible for testing. A test was performed for 24 women: no BRCA pathogenic variant was found. Among mammographic screening attendees, educational material with a simple description of FH may improve self-referral of women deserving an in-depth evaluation for HBOC identification. Additional educational efforts are needed to enhance the efficiency of the intervention.