Universal genetic testing for women with newly diagnosed breast cancer in the context of multidisciplinary team care

Abstract

Objective To determine the feasibility of universal genetic testing of women with newly diagnosed breast cancer, to estimate the incidence of pathogenic gene variants and their impact on patient management, and to evaluate patient and clinician acceptance of universal testing. Design, setting, participants Prospective study of women with invasive or high grade in situ breast cancer and unknown germline status discussed at the Parkville Breast Service (Melbourne) multidisciplinary team meeting. Women were recruited to the pilot (12 June 2020 – 22 March 2021) and expansion phases (17 October 2021 – 8 November 2022) of the Mutational Assessment of newly diagnosed breast cancer using Germline and tumour genomICs (MAGIC) study. Main outcome measures Germline testing by DNA sequencing, filtered for nineteen hereditary breast and ovarian cancer genes that could be classified as actionable; only pathogenic variants were reported. Surveys before and after genetic testing assessed pilot phase participants’ perceptions of genetic testing, and psychological distress and cancer‐specific worry. A separate survey assessed clinicians’ views on universal testing. Results Pathogenic germline variants were identified in 31 of 474 expanded study phase participants (6.5%), including 28 of 429 women with invasive breast cancer (6.5%). Eighteen of the 31 did not meet current genetic testing eligibility guidelines (probability of a germline pathogenic variant ≥ 10%, based on CanRisk, or Manchester score ≥ 15). Clinical management was changed for 24 of 31 women after identification of a pathogenic variant. Including 68 further women who underwent genetic testing outside the study, 44 of 542 women carried pathogenic variants (8.1%). Acceptance of universal testing was high among both patients (90 of 103, 87%) and clinicians; no decision regret or adverse impact on psychological distress or cancer‐specific worry were reported. Conclusion Universal genetic testing following the diagnosis of breast cancer detects clinically significant germline pathogenic variants that might otherwise be missed because of testing guidelines. Routine testing and reporting of pathogenic variants is feasible and acceptable for both patients and clinicians.

Universal Germline-Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision-Making

“…Similarly, De Silva et al found that in a cohort of Australian patients with breast cancer, universal GGT resulted in changes in clinical management for 77% of individuals. 48 Of note, VUS were not reported to patients in this study to avoid anxiety, unnecessary treatments, and undue burden on cancer clinics. Although VUS were reported in our study, nondisclosure of VUS may be an attractive option, especially for nongenetics providers implementing universal GGT.…”

“…A number of studies have demonstrated that current guidelines miss patients with actionable PGVs, preventing them from receiving genetics-informed care. 22 , 37 , 42 , 47 , 48 It has been suggested that GGT results may result in deviation from management guidelines. In 20,568 women with BC who underwent GGT, Kurian et al found that women with PGVs in BC predisposition genes were more likely to overuse BLM and chemotherapy and to underuse RT compared with patients with negative results.…”

MAGENTA: a Multinational patient survey assessing the Awareness, perceptions and unmet needs in GENetic Testing and counselling among patients with breAst cancer

“…Interestingly, in Australia, where mainstreaming of genetic testing and counselling has removed cost as a major impediment, a considerable proportion of women are unable to get tested due to the extremely stringent eligibility criteria. The Mutational Assessment of newly diagnosed breast cancer using Germline and tumor genomICs (MAGIC) study found that 31 out of 474 study participants were carriers of pathogenic variants in cancer-associated genes ( 13 ). However, 18 out of those 31 participants would be ineligible for routine genetic testing per the local testing guidelines ( 13 ).…”

“…While cost is not a significant barrier to testing in Australia due to mainstreaming of genetic testing for several breast cancer genes, the restrictive eligibility criteria result in a considerable proportion of at-risk women not receiving the benefits of genetic testing and counselling ( 12 , 13 ). Absence of a clear family history due to sociocultural factors also contributes to limited uptake of genetic testing and counselling in Australia.…”

BRCA testing and management of BRCA-mutated early-stage breast cancer: a comprehensive statement by expert group from GCC region

“…Studies on universal testing indicate that guidelines should be broadened to encompass testing of all patients diagnosed with BC ( 65 – 67 ). Researchers report that universal genetic testing after BC diagnosis can uncover clinically significant germline pathogenic variants that might otherwise escape detection due to narrow selection criteria as per current testing guidelines ( 66 ).…”