Clinical Behavior of Breast Cancer in Young Carriers and Prediagnostic Awareness of Germline Status.

Purpose

To investigate the clinical behavior of breast cancer in young carriers according to the specific gene () and the association of the timing of genetic testing (before at diagnosis) with prognosis.

Methods

This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in or , who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306).

Results

Compared with carriers (n = 1,683), carriers (n = 3,069) had more frequently hormone receptor-negative (74.4% 15.5%) and high-grade (77.5% 49.1%) tumors. Similar outcomes were observed in and carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% 32.4%), less nodal involvement (N0: 65.9% 50.8%), less frequently received chemotherapy (84.4% 92.9%), and axillary dissection (37.5% 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]).

Conclusion

This global study provides evidence on the different clinical behavior of breast cancer in young and carriers. Identifying a PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.

COI Statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

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