This work is still early, but it's been interesting to see a lab-based correlate emerge along with with the observation of women, and particularly older women, doing better in lung cancer studies (several prior posts here). Last year, the folks at Cell Therapeutics, Inc., analyzed results from their trials with Xyotax (post here), which demonstrated that their favorable results were seen in younger women. Estrogen may be very relevant to several biological processes related to lung cancer (reviewed in this post), so there is reason to believe that sex differences in lung cancer outcomes are plausible.

Results at ASCO this year were notable for a couple of presentations that noted a correlation of estradiol levels with lung cancer outcomes. Estradiol is the major form of estrogen in humans, the "female" hormone, although levels are present in men as well. The results for women under 60 vs. 60 and older in a couple of xyotax trials were broken down by estradiol levels. Women with lower estradiol levels did better regardless of their age, while those with higher estradiol levels did less well, again regardless of their age:

(Click to enlarge)

So age appears to be more of a surrogate for hormonal status than an independent prognostic factor, at least according to an early analysis.

It would be interesting, though, to see if estradiol levels were also prognostic in men, since men also have detectable levels. In fact, that was looked at in the Xyotax trials, and would you believe that the men with lower estradiol levels (below the median) had a significantly longer survival than the men with higher estradiol levels? Here's the figure for the results, among 318 of 583 men on the STELLAR-3 (carbo/taxol vs. carbo/xyotax) or STELLAR-4 trial (gemcitabine or navelbine vs. xyotax) who had serum samples available:

Note: Estradiol levels are measured differently than in the above curve in women, hence the different numbers (scale).

Unlike women on these xyotax trials, men didn't do better with xyotax regardless of their estradiol levels.

There are trials that are just now beginning to look into using anti-estrogen therapies like tamoxifen or faslodex (fulvestrant) in combination with tarceva or other anti-cancer strategies, to see whether they will confer the survival benefit that seems to be present for post-menopausal women to pre-menopausal women, or maybe even men. Right now, we haven't seen the results of these trials, but I'll be watching for more and will keep everyone posted if we learn more.