High likelihood of actionable pathogenic variants in breast cancer genes in women with very early onset breast cancer

  1. Gareth Evans

University of Manchester, Manchester, United Kingdom


Objectives:Early age at onset of breast cancer is a known risk factor for hereditary predisposition: To identify rates of BRCA1, BRCA2 and TP53 pathogenic variants (PVs) in very young breast cancers.

Methods: Women with breast cancer diagnosed aged ≤30 years where obtained from two sources:A population based study of 283 women diagnosed sequentially 1980-1997 in North West England and from referrals to the Manchester Genomic Medicine Department, 1990-2018. Sequencing of BRCA1, BRCA2 and TP53 was performed alongside tests for copy number variants, those testing negative underwent a full panel of 14 breast cancer associated genes.

Results: In total 352 women with breast cancer aged ≤30years were tested, 69 PVs in BRCA1(19.7%), 33 BRCA2(9.4%) and 20 TP53(5.7%) were identified. Testing of 172 negative women identified only 10 additional PVs (PALB2=3,CHEK2=3,ATM=3,PTEN=1). CHEK2 c.1100DelC was less common in the ≤30years population than in older women, whilst BRCA1/2 were more common in women aged 26-30 than younger women(p=0.009), whereas TP53 showed the reverse trend(p=0.008). Manchester score was highly predictive of BRCA1/2/TP53 PVs with only 3/95 (3%) of those with scores <15 having a PV and 30/30 (100%) of those ≥40. Surprisingly 9/21(43%) with DCIS had a PV(TP53=6), as common as triple negative 48/11(BRCA1=42), with 7/37(19%) of Her2+ with TP53 PVs.

Conclusions: Rates of BRCA1/BRCA2/TP53 PVs are extremely high in breast cancer ≤30 years, with limited benefit from additional panel testing. Certain breast pathologies such as DCIS, triple negative and HER2+ are strongly predictive of particular gene associations.