key: cord-0875391-bhsw2wv4 authors: Benusiglio, Patrick R.; Korenbaum, Clément; Vibert, Roseline; Ezenfis, Joël; Geoffron, Sophie; Paul, Charlotte; Richard, Sandrine; Byrde, Veronique; Lejeune, Manon; Guillerm, Erell; Basset, Noemie; Lotz, Jean-Pierre; Chabbert-Buffet, Nathalie; Gligorov, Joseph; Coulet, Florence title: Utility of a mainstreamed genetic testing pathway in breast and ovarian cancer patients during the COVID-19 pandemic date: 2020-11-10 journal: Eur J Med Genet DOI: 10.1016/j.ejmg.2020.104098 sha: 60f5600e566f38b0664fb8cec01176aeef85ebe3 doc_id: 875391 cord_uid: bhsw2wv4 INTRODUCTION: Mainstreamed genetic testing (MGT) obviates the need for a cancer genetics consultation, since trained oncologists (O) and gynaecologists (G) provide counseling, prescribe testing and deliver results. We report results from our MGT program and emphasize its utility during the COVID-19 lockdown, when cancer genetics clinics had suspended their activity. METHODS: An MGT pathway for breast and ovarian cancer (BC/OC) patients was established in Jan-2018 between the Assistance Publique - Hôpitaux de Paris.Sorbonne Université Cancer Genetics team and the Oncology/Gynecology departments at one teaching and two regional hospitals. Trained O + G evaluated patients with the Manchester Scoring System. A 12-point threshold was recommended for testing. Next-generation sequencing of BRCA1, BRCA2, PALB2, RAD51C and RAD51D was performed. Results were delivered to the patient by O/G. Pathogenic variants (PV) carriers were referred to the genetics clinic. Results are reported for the 2nd-Jan-2018 to 1st-June-2020 period. That includes the eight-week COVID-19 lockdown and three-week de-confinement phase 1. RESULTS: Results were available for 231/234 patients. Twenty-eight (12.1%) carried a PV. Of the 27 patients tested during the COVID-19 period, three carried a PV, two in BRCA1 and one in RAD51C. The clinical impact was immediate for the two BRCA1 BC cases undergoing neo-adjuvant chemotherapy, since double mastectomy and salpingo-oophorectomy will now be performed using two-step strategies. CONCLUSIONS: MGT guaranteed care continuity in BC/OC patients during the critical phases of the COVID-19 pandemic, with immediate implications for PV carriers. More broadly, we report for the first time the successful implementation of MGT in France. On 16 th March 2020, as the exponential increase in COVID-19 cases was threatening to overwhelm the French health care system, the country went into lockdown. People were not allowed outdoors but for very specific reasons, and working from home became normal for most individuals. Non-urgent medical care, including clinical cancer genetics, was suspended or drastically reduced in order to minimize patients' and medical professionals' exposure to the virus. Mainstreamed genetic testing (MGT) obviates the need for a cancer genetics consultation for most eligible cancer patients, since trained oncologists (O) and gynecologists (G) provide genetic counseling, prescribe germline testing and deliver results (1) . Only complex cases and pathogenic variant (PV) carriers are referred to the cancer genetics team. It was only proposed recently as an alternative to traditional cancer genetics clinics-based pathways (2) . Following reports from the United Kingdom of favorable outcomes in ovarian cancer (OC) patients (2), we implemented MGT in breast and ovarian cancer (BC/OC) patients for the first time in France at one teaching and two regional hospitals in the Paris region. We report herein our results and show how it guaranteed continuity of care during the COVID-19 lockdown and de-confinement phase 1. An MGT pathway for BC/OC patients was established in January 2018 between the Assistance Publique -Hôpitaux de Paris (AP-HP) .Sorbonne Université Cancer Genetics team and the Oncology and Gynecology departments at Tenon University Hospital (Paris), Centre Hospitalier Sud Francilien regional hospital, and Groupe Hospitalier de l'Est Francilien regional hospital. Its aims were to improve access to testing in patients from the Ile-de-France region living far from Paris-based genetics clinics, and to bypass increasing consultation waiting times. Approval was obtained from the Institut Universitaire de Cancérologie -Sorbonne Université scientific committee. corresponds to a 6-10% PV detection rate in the BRCA1-BRCA2 major BC/OC susceptibility genes in a British population (3, 4) . O/G provided basic genetic counseling and prescribed testing at or shortly after cancer diagnosis. Patients were given an one-page document summarizing the information given during a traditional cancer genetics consultation. On February 4 th , 2020, an educational video created with the Geneticancer patient association was made available online to patients (https://www.youtube.com/watch?v=5YzBOw8jxeI&t). Blood was drawn immediately afterwards. O/G could contact the cancer genetics team at any stage of the process. Although the MGT program was developed for BC/OC patients, testing prescription was tolerated in patients with other cancers when the context was suggestive of BRCA1-2/PALB2/RAD51C-Dassociated susceptibility. A single academic laboratory centralized testing, using a next generation sequencing panel including the BRCA1, BRCA2, PALB2, RAD51C and RAD51D genes. Results were delivered to the patient by O/G, or at the O/Gs' request, by the cancer geneticist. All PV carriers had to be referred to the cancer genetics clinic. Multidisciplinary team discussion of cases for whom no PV was identified was encouraged. Variants of unknown significance were discussed on a case by case basis. Results are reported for the 2 nd January 2018 to 1 st June 2020 period. That includes the eight-week COVID-19 lockdown (16 th March -11 th May 2020) and the following three weeks (de-confinement phase 1) when travelling restrictions were still present, hospital activity had not returned to normal, and most patients were reluctant to attend non-essential consultations. A total of 234 patients had MGT ( Two are yet to accept and one died. Of the 27 patients tested during the COVID-19 period, three carried a PV, two in BRCA1 and one in RAD51C. The two BRCA1 PV carriers were female patients aged 40 (patient 1) and 54 (patient 2) with triple-negative ductal breast cancer, bilateral and unilateral respectively. Both were undergoing neoadjuvant chemotherapy at the time of writing. Given the genetic results, patient 1 will now have bilateral mastectomy instead of the initially-planned double lumpectomy. Risk-reducing salpingooophorectomy will be scheduled afterwards. As for patient 2, lumpectomy will be performed, but in association with reduction mammoplasty and risk-reducing salpingo-oophorectomy. Double mastectomy will follow in the subsequent months. Regarding the RAD51C PV carrier, debulking surgery has just been performed after three cycles of chemotherapy. Monahan et al. recently predicted that the suspension of screening colonoscopies in Lynch syndrome patients during the COVID-19 pandemic, and their only slow resumption afterwards, would result in an excess of advanced-stage colorectal cancer diagnoses (5) . In the English population as a whole, substantial increases in the number of avoidable cancer deaths in England are predicted as a result of diagnostic delays (6) . As for genetic susceptibility to BC/OC, we expect that the unavailability of J o u r n a l P r e -p r o o f genetic testing will lead to suboptimal cancer treatment and risk management in patients carrying PV, and as a result in avoidable deaths in the long term. France, but slightly higher than rates reported in British patients (3, 4) . This warrants further exploration. Finally, all but two eligible PV carriers have attended the recommended cancer genetics consultation. Flaum et al. also reported that a small minority (2/39) of PV carriers identified via MGT pathways in Northwestern England declined their cancer genetics appointment (4). Nevertheless, long-term risk management and the importance of cascade testing in relatives have been addressed by an expert team in the vast majority of cases from our series, and we are hopeful that in the end the two remaining patients will understand the importance of a referral to our cancer genetics clinic. Gligorov: Roche-Genentech, Novartis, Onxeo, Dachii Sankyo, MSD, Isai, Genomic Health, Ipsen, Macrogenics, Pfizer, Mylan, Lilly, Immunomedics, Sandoz. Honoraria or symposium/travel funding. Groupe Hospitalier Pitié-Salpêtrière Equipe Instabilité des Microsatellites et Cancer, 184 rue du Hôpital Tenon, AP-HP .Sorbonne Université, 4 rue de la Chine Hôpital Tenon, AP-HP .Sorbonne Université, 4 rue de la Chine Centre Hospitalier Sud Francilien, avenue Serge Dassault, F-91106 Groupe Hospitalier de l'Est Francilien, Site Marne-la-Vallée, 2-4 cours de la Gondoire, F-77600 Jossigny, France. *Corresponding author: Consultation d'Oncogénétique -UF d'Oncogénétique REFERENCES Mainstreamed genetic testing for women with ovarian cancer: First-year experience Implementing rapid, robust, costeffective, patient-centred, routine genetic testing in ovarian cancer patients. Sci Rep Pathology update to the Manchester Scoring System based on testing in over 4000 families Mainstreaming germline BRCA1/2 testing in non-mucinous epithelial ovarian cancer in the North West of England Management strategies for the colonoscopic surveillance of people with Lynch syndrome during the COVID-19 pandemic The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study Mainstreamed genetic testing for women with ovarian cancer: first-year experience Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer We are grateful to Laetita Mendes and Elisabeth Boissin from the Geneticancer patient association, and to Anais Fouet. They conceived and created with our collaboration the genetic susceptibility to breast and ovarian cancer information video (https://www.youtube.com/watch?v=5YzBOw8jxeI&t). Study concept and design: Benusiglio, Ezenfis, Byrde, Chabbert-Buffet, Gligorov, Coulet. Acquisition, analysis, or interpretation of data: all authors Drafting of the manuscript: Benusiglio