Do customers miss your "We can't ship to PO Boxes" message? You can now prevent them from placing the order...
You'll also need to prefix the above expression with a check for null, because during a Shipping Estimate (as opposed to checkout), there is no Address1. So, the final expression looks like this:
ShippingAddress.Address1 != null and Regex.IsMatch(ShippingAddress.Address1, "(?i)\b(?:Post\ (?:Office\ )?|P[.\ ]?O\.?\ )?Box\b")
