Management of BRCA Tumour Testing in an Integrated Molecular Tumour Board Multidisciplinary Model

Jacopo Azzollini; Andrea Vingiani; Luca Agnelli; Elena Tamborini; Federica Perrone; Elena Conca; Iolanda Capone; Adele Busico; Bernard Peissel; Erica Rosina; Monika Ducceschi; Mara Mantiero; Salvatore Lopez; Francesco Raspagliesi; Monica Niger; Matteo Duca; Silvia Damian; Claudia Proto; Filippo de Braud; Giancarlo Pruneri; Siranoush Manoukian

doi:10.3389/fonc.2022.857515

Management of BRCA Tumour Testing in an Integrated Molecular Tumour Board Multidisciplinary Model

Front Oncol. 2022 Apr 8:12:857515. doi: 10.3389/fonc.2022.857515. eCollection 2022.

Authors

Jacopo Azzollini¹, Andrea Vingiani^{2

3}, Luca Agnelli^{2

4}, Elena Tamborini², Federica Perrone², Elena Conca², Iolanda Capone², Adele Busico², Bernard Peissel¹, Erica Rosina¹, Monika Ducceschi⁵, Mara Mantiero⁵, Salvatore Lopez⁵, Francesco Raspagliesi⁵, Monica Niger⁴, Matteo Duca⁴, Silvia Damian⁴, Claudia Proto⁴, Filippo de Braud^{3

4}, Giancarlo Pruneri^{2

3}, Siranoush Manoukian¹

Affiliations

¹ Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
² Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
³ Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.
⁴ Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁵ Department of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Abstract

Tumour testing of the BRCA1/2 genes is routinely performed in patients with different cancer histological subtypes. To accurately identify patients with tumour-detected germline pathogenic variants (PVs) is a relevant issue currently under investigation. This study aims at evaluating the performance of the tumour-to-germline diagnostic flowchart model defined at our Institutional Molecular Tumour Board (MTB). Results from tumour BRCA sequencing of 641 consecutive unselected cancer patients were discussed during weekly MTB meetings with the early involvement of clinical geneticists for appropriate referral to genetic counselling. The overall tumour detection rate of BRCA1/2 PVs was 8.7% (56/641), ranging from 24.4% (31/127) in high-grade ovarian cancer to 3.9% (12/304) in tumours not associated with germline BRCA1/2 PVs. Thirty-seven patients with PVs (66%) were evaluated by a clinical geneticist, and in 24 of them (64.9%), germline testing confirmed the presence of the PV in blood. Nine of these patients (37.5%) were not eligible for germline testing according to the criteria in use at our institution. Cascade testing was subsequently performed on 18 relatives. The tumour-to-germline diagnostic pipeline, developed in the framework of our institutional MTB, compared with guideline-based germline testing following genetic counselling, proved to be effective in identifying a higher number of germline BRCA PVs carriers.

Keywords: BRCA1; BRCA2; HBOC (hereditary breast and ovarian cancer); genetic counselling; homologous recombination; ovarian cancer; somatic variants.

Copyright © 2022 Azzollini, Vingiani, Agnelli, Tamborini, Perrone, Conca, Capone, Busico, Peissel, Rosina, Ducceschi, Mantiero, Lopez, Raspagliesi, Niger, Duca, Damian, Proto, de Braud, Pruneri and Manoukian.