A report by the Microsoft 365 Defender Research team explained how attackers compromised admin accounts in a Microsoft 365 tenant. They then created a malicious OAuth app, granted the app some high-priority permissions, and used it to update the Exchange Online configuration to allow spam traffic to flow. All of this comes down to allowing attackers to compromise admin accounts.
One way to protect administrator mailboxes is not to use them. And if you want administrators to use separate mailboxes for their permissioned and non-permissioned activities, that's what you might do. However, we can be smarter and use transport rules to selectively block email sent to administrator mailboxes to dissuade internal people from sending email and blocking all but the most essential email coming in from external domains.
How to use Exchange Online mail flow rules to improve the effectiveness of your EOP spam filtering and protect Office 365 users from phishing attacks.