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. 2024 Sep 3;7(9):e2431427.
doi: 10.1001/jamanetworkopen.2024.31427.

Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer

Zoulikha Rezoug  1   2   3 , Stephanie P Totten  4 , David Szlachtycz  1   5 , Adrienne Atayan  1   2 , Kristen Mohler  1   2 , Sophie Albert  1   2 , Leila Feng  1   2 , Brianna Lemieux Anglin  1   2 , Zhen Shen  1 , Daniel Jimenez  2   5 , Nancy Hamel  2 , Nicholas Meti  6   7 , Khashayar Esfahani  6   7 , Jean-François Boileau  1   6   8 , Ipshita Prakash  1   6   8 , Mark Basik  1   6   8 , Sarkis Meterissian  2   8 , Francine Tremblay  8 , David Fleiszer  8 , Dawn Anderson  7   8 , George Chong  4   5 , Stephanie M Wong  1   6   8 , William D Foulkes  1   2   4   5   6
Affiliations

Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer

Zoulikha Rezoug et al. JAMA Netw Open. .

Abstract

Importance: Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases.

Objective: To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer.

Design, setting, and participants: This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024.

Results: Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors.

Conclusions and relevance: In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Boileau reported receiving grants and personal fees from AstraZeneca, Novartis, Pfizer, Merck, Roche, and Lilly; personal fees from Allergan, Exact Sciences, Veracyte, and Gilead; and grants from AbbVie and Bristol Myers Squibb outside the submitted work. Dr Foulkes reported receiving grants from AstraZeneca to support the biennial BRCA symposium, which is held in Montreal, Quebec, Canada. He is not involved in any of the negotiations for this support. No other disclosures were reported.

Figures

Figure.
Figure.. Cohort Selection and Genetic Testing Results
Of 729 women tested, 53 (7.3%) were identified with 54 germline pathogenic variants. aA single patient had 2 pathogenic or likely pathogenic variants in BRCA1 and CHEK2.
See this image and copyright information in PMC

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