Universal genetic testing of patients with newly diagnosed breast cancer — ready for prime time?

Silva, Dilanka L De; James, Paul; Mann, G. Bruce; Lindeman, Geoffrey J.

doi:10.5694/mja2.51317

Cited by 4 publications

(6 citation statements)

References 17 publications

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“…For people with newly diagnosed breast cancer, identification of a germline (heritable) mutation in a cancer predisposition gene, such as BRCA1 or BRCA2 , has important treatment implications. It can inform decisions about therapy, guide future cancer prevention strategies, and facilitate risk management of their blood relatives 1 …”

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

Silva

Skandarajah

Sinclair

et al. 2023

Medical Journal of Australia

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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.

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confidence: 99%

“…It can inform decisions about therapy, guide future cancer prevention strategies, and facilitate risk management of their blood relatives. 1 …”

mentioning

confidence: 99%

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

Silva

Skandarajah

Sinclair

et al. 2023

Medical Journal of Australia

Self Cite

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“…We assumed that gBRCAm status is known for every patient entering the model. Despite calls for universal germline genetic testing in all patients with newly diagnosed breast cancer, National Comprehensive Cancer Network guidelines still recommend testing based on risk factors associated with clinical presentation, personal health history, and family history . The availability and effectiveness of adjuvant olaparib for patients with gBRCAm is likely to prompt increased testing among patients with newly diagnosed early-stage breast cancer.…”

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confidence: 99%

“…Despite calls for universal germline genetic testing in all patients with newly diagnosed breast cancer, National Comprehensive Cancer Network guidelines still recommend testing based on risk factors associated with clinical presentation, personal health history, and family history. 30 , 31 , 32 The availability and effectiveness of adjuvant olaparib for patients with gBRCAm is likely to prompt increased testing among patients with newly diagnosed early-stage breast cancer. A recent study of strategies to identify patients with breast cancer eligible for olaparib treatment reported that universal testing in patients with TNBC was cost-effective (ICER<$60 000 per QALY) compared with a selective testing strategy, and expanding testing to all patients with ERBB2-negative disease had a favorable ICER as well.…”

Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness of Adjuvant Olaparib for Patients With Breast Cancer and Germline BRCA1/2 Mutations

Zettler,

De Silva,

Blinder

et al. 2024

JAMA Netw Open

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ImportanceThe OlympiA trial found that 1 year of adjuvant olaparib therapy can improve distant disease-free survival and overall survival from early-stage breast cancer in patients with a germline BRCA1/2 mutation. However, olaparib, an oral poly-adenosine diphosphate ribose polymerase inhibitor, is estimated to cost approximately $14 000 per month in the US.ObjectiveTo estimate the incremental cost-effectiveness of adjuvant olaparib compared with no olaparib in eligible patients.Design, Setting, and ParticipantsIn an economic evaluation from a health care system perspective, the cost-effectiveness of adjuvant olaparib was analyzed using a Markov state-transition model. The model simulated costs and lifetime health outcomes of 42-year-old women with high-risk early-stage breast cancer and a known BRCA1/2 mutation who completed definitive primary therapy and neoadjuvant or adjuvant systemic therapy. The study was conducted from August 2021 to July 2023. The effectiveness of olaparib was based on the findings of the OlympiA randomized clinical trial, and other model parameters were identified from the literature. The model was calibrated to the 1-, 2-, 3-, and 4-year distant disease-free and overall survival observed in the OlympiA trial, and olaparib was assumed to reduce the risk of distant recurrence only in the first 4 years.ExposureOne year of adjuvant olaparib or no adjuvant olaparib.Main Outcome and MeasureIncremental cost-effectiveness ratio (ICER) in 2021 US dollars per quality-adjusted life-year (QALY) gained. All outcomes were discounted by 3% annually.ResultsIn the base case, adjuvant olaparib was associated with a 1.25-year increase in life expectancy and a 1.20-QALY increase at an incremental cost of $133 133 compared with no olaparib. The resulting ICER was approximately $111 000 per QALY gained. At a willingness-to-pay threshold of $150 000 per QALY, olaparib was cost-effective at its 2021 price and in more than 92% of simulations in probabilistic sensitivity analysis. The results were sensitive to assumptions about the effectiveness of olaparib and quality of life for patients with no disease recurrence.Conclusions and RelevanceIn this study, from a US health care system perspective, adjuvant olaparib was a cost-effective option for patients with high-risk, early-stage breast cancer and a germline BRCA1/2 mutation.

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“…The MAGIC study reported by De Silva and colleagues in this issue of the MJA was well positioned to examine both goals of mainstreaming 7 . The authors offered universal genetic testing to 474 Australian women with newly diagnosed or recurrent breast cancer.…”

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Moving breast cancer susceptibility gene testing into the mainstream

Wong

Foulkes

2023

Medical Journal of Australia

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Universal genetic testing of patients with newly diagnosed breast cancer — ready for prime time?

Cited by 4 publications

References 17 publications

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

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

Cost-Effectiveness of Adjuvant Olaparib for Patients With Breast Cancer and Germline BRCA1/2 Mutations

Moving breast cancer susceptibility gene testing into the mainstream

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