The TESTBREAST journey: Revisiting the importance of early detection by frequent screening of women at high risk of breast cancer

Abstract

Women with an inherited pathogenic variant (PV) in a breast cancer (BC) susceptibility gene, or familial predisposition (FP) have an increased risk to develop BC. There is a need for improvement of screening methods due to interval cancers and radiation exposure. The aim of the TESTBREAST study is to develop a blood test suitable for early diagnosis. Here, the clinical composition of participants is provided. From 2010 to 2022, 1108 women were included in the TESTBREAST study, with currently 750 participants suitable for serum analysis. The median follow-up was 7 years [1-14]. Of the 1108 participants, 70% (n = 728) had a PV. BC was diagnosed in 16.5% (n = 124), mainly stage I-II (68.5%), and mostly BRCA1 (n = 47, 47%) and BRCA2 (n = 29, 29%) carriers. Invasive cancer was diagnosed in 100 cases: 76% (n = 76) had a PV with a median age of 49 [26-68] at diagnosis, whereas 24% (n = 24) had a FP, with a median age of 51 years [25-65]. The general population (the Netherlands) is aged 61 years on average at diagnosis. Triple negative breast cancer (TNBC) occurred in 51% (n = 39) of the TESTBREAST women with a PV, whereas this was 11% in the general population. Within the TESTBREAST cohort, BRCA carriers were younger at diagnosis and often had the aggressive TNBC subtype. Improvement of current screening methods for early detection is especially important for this group of high-risk women to reduce interval cancers, exposure to radiation, and to improve survival.

Keywords: breast cancer; germline mutation; hereditary breast and ovarian cancer; high‐risk; screening.

FIGURE 1

(A) Tumor stage among TESTBREAST participants diagnosed with breast cancer (n = 124); stage I (53.4%), stage II (19.8%), stage III (4.3%), stage IV (1.7%), in situ (DCIS and LCIS: 20.7%). (B) stage among patients of the national registry; stage I (40%), stage II (35%), stage III (8%), stage IV (5%), DCIS (12%).

FIGURE 2

(A) Breast cancer subtypes in the entire TESTBREAST cohort (n = 100); luminal A (49.0%), luminal B (3.1%), HER2‐enriched (1.0%), TNBC (44.8%), luminal A and B (2.1%). (B) subtypes in the national registry; luminal A (77%), luminal B (8%), HER2‐enriched (4%), TNBC (11%). (C) subtypes in TESTBREAST patients with familial predisposition (n = 24); luminal A (70.8%), luminal B (8.3%), HER2‐enriched (4.2%), TNBC (16.7%), luminal A and B (0%). (D) subtypes in TESTBREAST patients with proven genetic risk (n = 76); luminal A (41.7%), luminal B (1.4%), HER2‐enriched (0%), TNBC (54.2%), luminal A and B (2.8%). (E) Breast cancer subtypes in TESTBREAST patients with a BRCA1 mutation (n = 47); luminal A (22.7%), luminal B (0%), HER2‐enriched (0%), TNBC (75.0%), Luminal A and B (2.7%). (F) subtypes in TESTBREAST patients with a BRCA2 mutation (n = 29); luminal A (71.4%), luminal B (3.6%), HER2‐enriched (0%), TNBC (21.4%), Luminal A and B (3.6%).