In a locoregionally advanced breast cancer with multiple positive surgical margins, how safe is it to wait for a re-excision vs treating upfront with comprehensive RT if surgery cannot be done the short term due to the COVID outbreak?

Agreed, higher radiation dose will not replace negative margins. Obtaining negative margins is ideal. If the patient is a systemic therapy candidate, I would agree with @Dr. First Last and proceed with systemic therapy and then re-excision.

At our institution, we let the patient continue systemic treatment (AI or chemo based on phenotype) with plan for re-excision once COVID-19 settles down and then RT.