I use JShop for all my shops and all my clients, and we've got some shops with several thousand products running fine. 12,000 products is nothing in database terms - it's just 12,000 rows in a database table so even if you are joining multiple tables as long as everything indexed properly and queries are sound, you shouldn't have any problems. Even free software like osCommerce, ZenCart etc should be fine.
The biggest issue with 12,000 products is less the shopping cart itself but more of product management.
You need 12,000 descriptions.
You need to track 12,000 inventory items.
You need to manage 12,000 potential shipping variations.
For example the big issue in that many skus is incorporating products, descriptions, details and managing them. Does your software tie into your inventory/distribution system to reflect product levels & availability? Can you import etilize/spex/cnet product data or descriptions/pics directly from your vendor?
SEO, Checkout API, Ease of Search/finding are all important and many carts support these features however product management from store to customer will be the biggest issue you face with that many skus.