Germline genetic testing for pathogenic variants (PVs) in breast cancer (BC) genes is currently triggered by algorithms that assess the likelihood of PVs in specific patient populations.1 Testing in patients with BC in England was updated in April 2022, making it more widely available, including all women diagnosed <40 years, except those with grade 1 disease.2 However, this exception was recently dropped, apparently to simplify the testing algorithm. We have assessed the likelihood of a PV in BRCA1/2 in grade 1 versus grade 3 ER+HER2- breast cancer showing much higher rates in older women (40–49 years) with grade 3 disease than those <40 with grade 1.

Genetic testing strategies for BC in Europe are primarily targeted at individuals affected with cancer based on PV likelihood with testing of relatives usually only offered if a PV is identified in an index relative.1 More recently, European guidelines are now driven by the potential for gene-level directed management strategies such as poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) in persons with BC.3 In view of the evidence of efficacy for PARPi in earlier stage BC,4 further expansion of the testing criteria is likely to be implemented. A key question is whether this should be offered to all people with BC or whether a threshold should still be used, based on overall likelihood of PV detection, potentially incorporating likely future benefit from PARPi.

We have shown very low rates of PVs in patients with grade 1 breast cancer (G1BC) (0/156) in a population-based study of 1061 women with BCs5 compared with 11 out of 152 (7.2%) for patients with ER+HER2- G3BC (p=0.0003). We have also demonstrated …