Wibowo E, Pollock PA, Hollis N, Wassersug RJ
Andrology. 2016 Sep;4(5):776-88. doi: 10.1111/andr.12197. Epub 2016 May 6
Most male breast cancer is hormone dependent, via estrogen (ER/PR positive i.e. estrogen receptor, progesterone receptor positive). This is, on the whole, good news as it means the cancer cells are dependent (at least initially) on a signal coming from estrogen via its receptor for survival. Cut that off, and the cells mostly die, or at least become dormant. This is why for many men with breast cancer hormone therapy is the most effective part of their treatment plan.
That means we get Tamoxifen, as there is no data in support of other types of hormone therapy (actually there is little data either way as I have discussed in another post). That Tamoxifen has side effects is widely known, especially for women, because larger studies have been done for them on this subject. For men there is less evidence available, and Wibowo and colleagues have done a great service in pulling together what there is to survey the situation of Tamoxifen complications for men.
Wibowo and colleagues searched the literature for trials on Tamoxifen, and found 14 randomized clinical trials (the most valuable kind of trial design) on men receiving Tamoxifen though none of these were on men with breast cancer (they were for prostate cancer, infertility and gynecomastia). They also found 39 non-randomized clinical trials (a lower level of evidence), 11 of which were on men with breast cancer.
Overall there are relatively speaking few adverse effects, and it is relatively rare that men stop taking their Tamoxifen because of them (I say relatively as compared to, for example most chemo). Focusing on the data for men with breast cancer, the authors find that the most common type of adverse effect was psychiatric (~30%), including decreased libido, anxiety and sleep disorders. Cardiac and vascular disorders were rarer (~10%), but were more often serious health threats.
Over the entire study the discontinuation rate was small – around 5%. Interestingly for men with breast cancer it was higher at 10%.
The news is good – an effective therapy is mostly well tolerated and leads to few adverse effects that result in discontinuation.
My main concern, though, is how well the studies surveyed here for male breast cancer represent the experience of the now thousands of men on this drug. The higher discontinuation rate may well relate to the longer duration of treatment for men with breast cancer, which is typically 5 or even 10 years now. The trials for the other conditions had treatment durations of a few months to 3 years. Perhaps men faced with a significantly longer duration are less willing to endure? I think that what is necessary is a long-term, large population study on Tamoxifen adherence in men with breast cancer, such as are being undertaken for women.
The authors also report biochemical changes from some of the trials they report for disease other than male breast cancer. Very interestingly there is no consensus on the impact of Tamoxifen on E2 (estradiol) levels with trials reporting increases, decreases and no change. Similarly testosterone levels were sometimes seen to go up, and in other cases not to change or more rarely to decrease. The basis for this is unclear – there are likely feedback mechanisms in play, and reduction in ER signaling may cause such changes, but it is clearly not a simple relationship.
Another aspect of estrogen biology the authors discuss is the findings of ER functions in different brain regions that have been made over the past 10 or 15 years. These allow for the hypothesis that the psychiatric effects seen with Tamoxifen are due to direct effects on brain function rather than downstream of changes in systemic hormone levels. This of course requires more study, but raises the hope that perhaps in the future the brain could be spared from the hormone therapy, reducing the side effects that men (and women) suffer.