Male order.

We have a lot to learn when it comes to male breast cancers. Roughly 9 in 10 cases are hormone receptor positive with tamoxifen being the standard endocrine therapy of choice. The aptly named phase 2 MALE trial randomized 50 evaluable men to [1] tamoxifen alone versus [2] tamoxifen + a GnRH agonist versus [3] exemestane + plus a GnRH agonist. The primary endpoint of estrogen level at 3 months differed significantly across arms (even among so few men): +67% with tamoxifen (as expected with negative feedback from receptor blockade), -85% with tamoxifen + GnRH agonist, and -72% with exemestane + GnRH agonist. Now, this only informs estradiol levels, not cancer outcomes, but associations between lower estradiol levels and increased cancer survival in premenopausal women has been studied extensively. Finally, all of this should be balanced with the observation that sexual function and quality of life decreased with the addition of GnRH agonists. | Reinisch, JAMA Oncol 2021

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