Shortly after posting my latest tumor board presentation, I discovered that someone is making a documentary about men with breast cancer. The preview looked interesting:
During a brief Twitter exchange with the movie’s official account, the subject of no randomized clinical trials specificaly targeting men with breast cancer came up. Now, I don’t know why there aren’t any, but to have some fun speculating:
- Many large clinical trials with tens of thousands of women—and a few men—have already been published. We know that the biology and outcomes between men and women are similar, so spending resources on answering male-specific questions would be wasteful.
- Even if there were clinicaly relevant questions, male breast cancer is so rare that a good randomized controlled trial would never be able to get enough patients.
The first point is easily refuted. The only data comparing outcomes in men and women comes from a 1997 UK study. Treatment has changed significantly since then. Furthermore, most breast cancers in men have estrogen and/or progesteron receptors. Since Tamoxifen binds to the receptors we suspect its effect in men and women is the same. Aromatase inhibitors (AIs) and GnRH analog(u)es like Letrosole, however, affect estrogen production, which is markedly different in the two sexes. The difference may—and likely does—translate into different efficacy, tolerability, and side-effect profile. Does Tamoxifen work better than an AI when given adjuvantly, or for metastatic disease? Most likely. Would an AI combined with a GnRH analoge be better, same, or worse than Tamoxifen? We haven’t a clue.
Yes, it is an obvious question, and yes, there was an attempt to answer it. It couldn’t enroll enough patients in reasonable time, though, and closed prematurely without results. This brings up the second point—are there enough patients per year to have a phase III trial?
In brief, yes. If you are looking for a large enough effect size that has clinical significance along with a statistical one, you do not need a huge sample size for a well-powered study. The NCI has a randomized trial open for patients with adrenocortical carcinoma, a disease that is ten times less common than male breast cancer. Between advocacy groups, social media, and clinicaltrials.gov, it has never been easier for patients to find trials and vice versa. You do need to have a trial open, though.