全乳がん患者の遺伝子検査：GET FACTS無作為化臨床試験

Increasing germline genetic testing rates may impact contralateral prophylactic mastectomy (CPM) rates in patients with newly diagnosed breast cancer.

To quantify the impact of a personalized contralateral breast cancer (CBC) risk counseling tool that incorporates genetic testing results.

This randomized clinical trial recruited participants from a single tertiary referral center between June 8, 2020, and December 31, 2022. Patients aged 18 to 80 years with unilateral breast cancer who underwent genetic counseling and surgery were eligible. Exclusion criteria were prior or metastatic breast cancer or prior multigene panel testing. Follow-up was completed June 30, 2023.

Personalized age-specific CBC risks were estimated based on the presence or absence of pathogenic variants associated with breast cancer and were incorporated into a visual decision support tool. Patients were randomized 1:1 to quantitative counseling via the tool vs standard counseling without personalized CBC risk estimates.

Co-primary end points included patients' personal CBC risk knowledge and propensity to undergo CPM, before and after counseling, by randomization arm. The secondary end point was CPM rate. Sample size calculations assumed postcounseling CBC risk self-assessments would be 5% different from baseline (SD, 20%). A total of 199 patients in each arm would achieve 80% power and 5% type I error (based on a 2-sample t test). Univariate and multivariate analyses were performed for each end point.

A total of 400 patients were randomized (mean [SD] age, 54 [11] years), and 54 were excluded after randomization, leaving 346 patients. Among 341 patients with data available, 21 (6.2%) were Asian or Pacific Islander, 18 (5.3%) were Black, 295 (86.5%) were White, and 7 (2.1%) were of other race; 33 of 330 patients with available data (10.0%) were of Ashkenazi Jewish ancestry. Seventy-five of 346 patients (21.7%) had a first-degree relative with breast cancer. Patients who received quantitative counseling more accurately reported their CBC risk estimates than those who received standard counseling by univariate (coefficient, -9.39; 95% CI, -14.86 to -3.93; P < .001) and multivariate (coefficient, -9.52; 95% CI, -16.50 to -2.51; P = .008) analyses. The type of counseling did not significantly impact perception of risk, self-reported propensity to undergo CPM, or CPM rates.

In this randomized clinical trial, patients more accurately described their calculated CBC risk after quantitative counseling. This improved knowledge did not impact decisions to undergo CPM. The CBC risk assessment tool is publicly available and can be used for preoperative discussions.

ClinicalTrials.gov Identifier: NCT04245176.