The Boston Elevation Dynamic
The one-two punch of a net downhill for the first 16 miles and then the hills of Newton. What this means is that the halfway point in Wellesley (just after those screaming co-eds), almost everyone is beaming with PR potential after checking their watches. But look more closely at the bottom of Heartbreak Hill, only 6 miles later, and those smiles will have turned to grimaces.
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Focus on Your Cadence
A nice high cadence, or quick turnover, will allow you to keep some speed without pounding your quads. Somewhere between 90-94 foot strikes per minute should be more than adequate; this could require some testing in your training to see how it feels.
Run the First Six Miles Conservatively
As the race execution section above notes, there's nothing really to be gained by putting time in the bank here in Boston. The hills of Newton and the under-rated rolling terrain of Brookline will make you pay dearly.
Instead, take the first six miles to run a slightly slower than goal pace effort; approximately 10 to 15 seconds slower. Take the immediate pressure off yourself and take in the sights. You have 20 miles to make up the minute you have lost, but you'll never get the chance to "cruise" again.
By the time the hills arrive, you'll be ready to just dominate them...but you can't. Remember the transition your legs have to make from running down to up, and help them out by keeping your stride compact and "spinning" your way up the hills.
More: Hill Running Made Easy
Do your best to maintain a steady effort, letting the pace drop a bit as you can make it up on the other side. If you force the issue too early, you could pay dearly when you need it most: the last 5.2 miles from the top of Heartbreak Hill to the finish line.