In a cross-sectional study reported in JAMA Network Open, Rezoug et al found that universal genetic testing identified immediately actionable and established germline pathogenic variants in more than 1 in 20 newly diagnosed patients with invasive breast cancer and was associated with systemic therapy recommendations for one-third of those affected.
Study Details
A total of 805 patients from three hospitals in Montreal who had a first diagnosis of pathologically confirmed stage I to IV breast cancer between September 2019 and April 2022 were eligible for inclusion. Of this population, 729 patients (90.6%) consented to be tested. The median age at diagnosis in the testing cohort was 53 years (range = 23–91 years); nearly two-thirds of these patients (65.4%) were White and of European ancestry.
Testing comprised an obligatory primary panel for B1B2P2, which included BRCA1/2 and PALB2, as well as an optional secondary panel for the following 14 additional breast cancer susceptibility genes: ATM, BARD1, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53. A total of 659 (90.4%) and 70 (9.6%) patients in the testing cohort opted to receive the primary panel with and without the secondary panel, respectively.
Key Findings
The investigators identified 54 germline pathogenic or likely pathogenic variants in breast cancer susceptibility genes in 53 patients (7.3%), including 39 (5.3%) in B1B2P2 and 15 (2.1%) in 6 of the additional 14 genes (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11).
Based on a multivariable analysis, the following clinical factors were independently associated with B1B2P2-positive status:
- Age younger than 40 at diagnosis (odds ratio [OR] = 6.83, 95% confidence interval [CI] = 2.22–20.90)
- Triple-negative disease (OR = 3.19, 95% CI = 1.20–8.43)
- High-grade disease (OR = 1.68, 95% CI = 1.05–2.70)
- Family history of ovarian cancer (OR = 9.75, 95% CI = 2.65–35.85).
Approximately one-third of the patients with B1B2P2-positive disease (n = 13; 33.3%) were deemed eligible for PARP inhibitor therapy.
The investigators concluded: “The results of this study and related studies have informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer who are younger than age 50, those with triple-negative and/or bilateral breast cancer, those potentially eligible for PARP inhibitors, and, unrelated to this study, male patients with breast cancer. Affected women who do not meet these criteria are referred to the medical genetics service for appropriate evaluation. As genetic testing evolves, publicly funded genetic testing programs will need to be evaluated for benefit and cost-effectiveness in clinical situations.”
William D. Foulkes, MBBS, PhD, of McGill University, Montreal, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was funded by the Jewish General Hospital Foundation, the Quebec Breast Cancer Foundation, and the Fonds de Recherche du Quebec Santé. For full disclosures of the study authors, visit jamanetwork.com.
