Would you consider partial breast irradiation in patients who otherwise meet PBI guidelines who have a pathogenic variant of CHEK2 or other moderate penetrance gene?  

I would favor whole-breast RT. Although we don’t have data on moderate penetrance genes, in BRCA mutation even whole breast prophylaxis data suggests less risk of a second new primary in these patients. Evron et al., PMID 30475942 

Let’s first level-set that this question assumes that such a patient has already made the (reasonable) decision to forego surgical prophylaxis. This comes with a lifetime of active surveillance with higher than “normal risk” post-treatment. In such a case, PBI (again, assuming the ...