Participants in population screening diagnosed with ESBC receive substantially less-intense treatment than non-participants. Differences persist when potential overdiagnosis is taken into account; these differences should be factored into debates around mammographic screening.
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.
Uptake of MDM-recommended treatments is high. There is a minority of patients in whom MDM recommendations are not followed, highlighting that there are extra steps between recommendations at an MDM and decisions with patients. More attention to this issue is appropriate, and the reasons for non-concordance warrant further study.
572 Background: Selective use of radiotherapy (RT) after surgery for early breast cancer (EBC) has been an elusive goal. The role of breast MRI in localised EBC is controversial. We aimed to determine if preoperative MRI could identify patients with EBC in whom the ipsilateral invasive recurrence (IIR) rate was sufficiently low without RT, such that RT might be safely omitted. Here we report primary and secondary outcomes, and imaging/biopsy findings for occult lesions. Methods: PROSPECT is a prospective single-arm study. Criteria for omission of RT included age at least 50, nil/minimal or mild Background Parenchymal Enhancement (BPE) on MRI, unifocal pT1N0 cancer, not Triple Negative (TNBC), no LVI. All patients who underwent PROSPECT MRI were included in the analysis. Imaging findings on MMG, US and MRI were documented and all biopsies were recorded. Pathology of lesions identified by MRI was described. The primary outcome was the IIR at 5 years of those treated without RT. An IIR rate of 5% or less was considered acceptable. The protocol specified primary analysis occurred after the 100th patient reached 5 years follow up in May 2021. Results: Between 9/2011 and 5/2019, 443 patients had MRI after diagnosis. BPE was nil/minimal or mild in 344 patients. MRI detected 194 occult lesions in 144 (33%) patients; 139 (72%) were ipsilateral. 61 MMG/US occult malignant lesions - 36 invasive and 25 DCIS - were identified in 48 patients (11% of total cohort). Of 38 ipsilateral lesions in 32 patients (7% of total cohort), 23 were DCIS, 4 were T1a, 7 T1b and 4 T1c. 201 patients were treated on trial without RT. The median age was 63 years (range: 50 to 84), median tumour size 11 mm (range: 2 to 20), grade 1 (104), grade 2 (86) or grade 3 (11). The rate of IIR at 5 years was 1% (1/101). There were 2 IIRs at 4.6 and 7.7 years follow up, 1 regional recurrence, and 1 patient with both a regional and distant recurrence with 1 breast cancer death. There was 1 contralateral (CL) breast cancer, 1 CL DCIS, 2 other cancer diagnoses and 1 death from other causes. Of 242 patients undergoing MRI but not in the main study, median age was 63 range: 50-80, median tumour size, 13mm (range: 4-145). 9 underwent mastectomy (2% of total cohort). Followup is complete for 235. There was 3 IIR, 3 CL primary and no distant metastases or breast cancer deaths. Conclusions: Breast MRI in selected, low risk patients identified occult malignancy in 11% of patients. At a median of 5 years follow up the IIR and other breast cancer events was very low. This suggests that local recurrences may be due to occult breast cancers, and MRI may allow the identification of truly localised cancers for which radiation may be safely omitted. The event rate for the entire cohort was very low, suggesting that identification of occult malignancy in apparently unifocal EBC is beneficial. Confirmatory trials are needed. Clinical trial information: 12610000810011.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.