If you want to maximize what SpamAssassin can do, you will probably have to train the bayesian filter that SA uses. Take a look at the SpamAssassin and Cpanel docs. It's just a matter of throwing messages at SA and telling it if these are spam or not.
We spent a few days fine tuning our own SpamAssassin installation with special rulesets (and lots of training) to reduce our spam load. Currently, we have 100% accuracy for over a week.
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