Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 May 10;43(14):1706-1719.
doi: 10.1200/JCO-24-01334. Epub 2025 Feb 24.

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

Matteo Lambertini  1   2 , Eva Blondeaux  3 , Loredana M Tomasello  1   4 , Elisa Agostinetto  5 , Anne-Sophie Hamy  6 , Hee Jeong Kim  7 , Maria Alice Franzoi  8 , Rinat Bernstein-Molho  9 , Florentine Hilbers  10 , Katarzyna Pogoda  11 , Hans Wildiers  12 , Jyoti Bajpai  13 , Michail Ignatiadis  5 , Halle C F Moore  14 , Ann H Partridge  15 , Kelly-Anne Phillips  16   17   18 , Angela Toss  19   20 , Christine Rousset-Jablonski  21 , Carmen Criscitiello  22   23 , Tiphaine Renaud  24 , Alberta Ferrari  25   26 , Shani Paluch-Shimon  27   28 , Robert Fruscio  29   30 , Wanda Cui  16   17 , Stephanie M Wong  31 , Claudio Vernieri  22   32 , Kathryn J Ruddy  33 , Maria Vittoria Dieci  34   35 , Alexios Matikas  36 , Mariya Rozenblit  37 , Cynthia Villarreal-Garza  38 , Laura De Marchis  39   40 , Fabio Puglisi  41   42 , Kenny A Rodriguez-Wallberg  43 , Francois P Duhoux  44 , Luca Livraghi  45 , Marco Bruzzone  3 , Luca Boni  3 , Judith Balmaña  46
Affiliations
Multicenter Study

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

Matteo Lambertini et al. J Clin Oncol. .

Abstract

Purpose: To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene (BRCA1 v BRCA2) and the association of the timing of genetic testing (before v 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 BRCA1 or BRCA2, 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 BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor-negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA 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% v 32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 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 BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.

PubMed Disclaimer

Conflict of interest 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).

Figures

FIG 1.
FIG 1.
Study flowchart. PV, pathogenic/likely pathogenic variant.
FIG 2.
FIG 2.
Survival outcomes in BRCA1 and BRCA2 carriers: (A) Epanechnikov Kernel-Smoothed annual hazard of DFS events overall, (B) DFS, (C) BCSS, and (D) OS. BCSS, breast cancer–specific survival; DFS, disease-free survival; OS, overall survival.
FIG 3.
FIG 3.
Survival outcomes in patients tested for germline BRCA status before or at diagnosis of breast cancer: (A) DFS, (B) BCSS, and (C) OS. BCSS, breast cancer–specific survival; DFS, disease-free survival; OS, overall survival.
See this image and copyright information in PMC

References

    1. Paluch-Shimon S, Cardoso F, Partridge AH, et al. ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5) Ann Oncol. 2022;33:1097–1118. - PubMed
    1. Rosenberg SM, Ruddy KJ, Tamimi RM, et al. BRCA1 and BRCA2 mutation testing in young women with breast cancer. JAMA Oncol. 2016;2:730–736. - PMC - PubMed
    1. Copson ER, Maishman TC, Tapper WJ, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): A prospective cohort study. Lancet Oncol. 2018;19:169–180. - PMC - PubMed
    1. Lambertini M, Peccatori FA, Demeestere I, et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2020;31:1664–1678. - PubMed
    1. Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline. Ann Oncol. 2023;34:33–47. - PubMed

Publication types

Associated data