Pathogenic Variant Prevalence Highlighted For Postmenopausal Breast Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Over 3% of postmenopausal breast cancer patients carry a pathogenic variant (PV) in a breast cancer-related gene, data from the Women’s Health Initiative (WHI) suggests. 

“Most guidelines do not address testing among postmenopausal women without hereditary risk factors, the most common subgroup of breast cancer patients, as PV prevalence data are lacking”, explain Allison Kurian, from Stanford University in California, USA, and co-investigators.

The team therefore used next-generation sequencing to assess for PVs in 28 genes – including BRCA1/2, ATM, BARD1, CDH1, CHEK2, PALB2, STK11 and TP53 – in 2195 WHI participants diagnosed with breast cancer at a median age of 73 years and 2322 controls who were aged a median of 81 years at their last follow-up.

This revealed that breast cancer patients were significantly more likely than controls to both carry a PV (6.74 vs 4.01%) and to test positive for a PV associated with breast cancer risk (3.55 vs 1.29%).

But just 30.8% of breast cancer patients and 20.0% of controls who tested positive for a BRCA1/2 PV would be recommended for genetic testing as per the US National Comprehensive Cancer Network 2019 guidelines, the researchers note. The eligibility rates for testing for other breast cancer-specific PVs were similar, at 34.0% and 16.0%, respectively.

The prevalence of BRCA1/2 mutations was 2.21% among breast cancer participants aged less than 65 years at diagnosis versus 1.09% among those who were 65 years or older at diagnosis, although there was no significant age-related difference in PV rates.

“Women diagnosed when younger than 65 years had similar probability of BRCA1/2 PVs as Ashkenazi Jewish individuals (≈2.5%), for whom testing is supported”, the researchers observe in a research letter to JAMA.

Allison Kurian and co-authors therefore advise: “These data on the prevalence of PVs in breast cancer susceptibility genes among postmenopausal women should inform testing guidelines. 

“Among postmenopausal patients with breast cancer, PV prevalence may be high enough to warrant testing even in the absence of early diagnosis age or family history.” 

Reference  

Kurian AW, Bernhisel R, Larson K, et al. Prevalence of pathogenic variants in cancer susceptibility genes among women with postmenopausal breast cancer. JAMA 2020; 323:995–997. doi:10.1001/jama.2020.0229