Another study reports cognitive decline with tamoxifen

I've posted about the breast cancer drug Tamoxifen before.  More than one study has suggested that this drug may cause or contribute to cognitive decline.

These are links to earlier posts on this topic:

http://adventureswithdementia.blogspot.co.uk/2011/10/possible-causescontributory-factors-2_16.html

http://adventureswithdementia.blogspot.co.uk/2011/11/more-on-tamoxifen.html

http://adventureswithdementia.blogspot.co.uk/2012/06/tamoxifen-again.html

This link is to a recent report on research which again suggests that Tamoxifen may be responsible for cognitive decline in some women:

www.examiner.com/article/another-study-reports-cognitive-decline-with-tamoxifen

New readers catch-up 2: Causes/contributory factors

In my effort to try and understand the disease, I've looked so far at three possible causes/contributory factors. Unlike some of the stuff that you can find online, these have all been discussed and researched by perfectly reputable scientists, and at least two of the three were taken seriously by the memory clinic and its very highly respected head.

Just click on the links which take you to various posts on this blog:

1) Lyme disease

2) Tamoxifen  and here  mice experiments

3) Herpes and here

(There's more on Herpes and the best way to find it all is to put the word into the search box (top left) and click 'enter')

Tamoxifen again

I've blogged about the possible link between Tamoxifen and memory/dementia:
here and here.

This is a link to an interesting article on this topic:
http://www.sciencedirect.com/science/article/pii/S0091305701006566.

Another interesting article  -  see the abstract at the start:
http://www.faceblind.org/social_perception/papers/zbasseda/zbasseda-Tamoxifen.pdf

Perhaps most interestingly, Tamoxifen appears to be a drug that researchers turn to when they wish, for whatever reason, to impair the memory of mice: as this link shows  -  and it's an interesting article in its own right: 'After being given tamoxifen (perhaps best known as a breastcancer drug) for eight days, an otherwise normally developing mouse had more than 80 percent fewer new neural stem cells in its hippocampus (a structure in the brain's frontal region linked to short-term memory).' And whereabouts in the brain is Alzheimer's first detected? In the hippocampus, I believe.

More on Tamoxifen

I've not had time yet to find the very detailed letter referred to in the previous Tamoxifen post. However I know the main problem with trying to pin down whether Tamoxifen can have adverse effects in the brain. It definitely crosses the blood/brain barrier. But the complication is that sometimes Tamoxifen acts like Oestrogen and sometimes it acts as an anti-Oestrogen. Its anti-Oestrogen manifestation is what makes it useful in relation to breast cancer, or at least in those breast cancers where Oestrogen plays a part.

It is unclear which effect Tamoxifen might have when it reaches the brain. A further complication is that it is unclear whether Oestrogen itself is beneficial or harmful to the brain; the research gives contradictory results. Unsurprisingly, in these circumstances, the small amount of research that has been done to try and determine whether Tamoxifen is good or bad for the brain is also inconclusive.

So someone like S who, on medical advice, was simultaneously taking Oestrogen (HRT) and Tamoxifen could have been adversely affected by either or both Or presumably the effects could have cancelled each other out, or they could both have had a beneficial effect. And her condition might have nothing to do with either of them!

It interests me that American scientists wanting to degrade the memories of mice used Tamoxifen to do so. These were 'transgenic mice' that had had their genes interfered with to enable this 'unusual' response to Tamoxifen. But this surely raises the possibility that humans with a particular genetic make-up could be similarly affected by Tamoxifen?

It is amazing to me that these scientists already knew about a link between Tamoxifen and memory yet no-one researching memory problems in humans seems to have made such a connection.

I will find the link to the report and post it here.

Possible causes/contributory factors 3/ TAMOXIFEN

Tamoxifen has been in use to treat breast cancer patients for several decades. Typically, it is used, either alone or in combination with chemotherapy, to treat women following surgery and appears fairly successful in preventing a recurrence of the disease.

S has not had breast cancer, but because her mother had it, and at a fairly early age, S has had regular mammograms and was invited to participate in the IBIS study designed to test whether Tamoxifen could have a protective effect against the development of breast cancer in women who might have a genetic pre-disposition towards the disease. (Actually, her mum's cancer was treated before there were tests to determine whether a particular cancer might benefit from Tamoxifen.)

S decided to participate in the trial. She was on HRT at the time, mainly because her mum was thought to be suffering from osteoporosis (though it was later decided that she wasn't). Those running the trial were aware that she was on HRT.

During the five year trial, S started to develop memory problems. She became convinced, before we ever knew anything about a possible connection, that Tamoxifen was the culprit. Shortly before the trial was due to end, she stopped taking the tablets (which might of course have been a placebo as this was a double-blind trial). Somewhere around this time she stopped the HRT also.

As things got worse, I started looking into Tamoxifen and found a surprising number of references to a possible link between Tamoxifen and memory problems. S eventually sought to discover whether she had actually been taking Tamoxifen or a Placebo and it was confirmed that she had been taking Tamoxifen.

We mentioned all this to the Professor at the memory clinic and he certainly didn't dismiss it out-of-hand (as he was quite prepared to do with other ideas).

I tried to find out from IBIS whether they had asked people on the trial if they had noticed problems with their memory (they sent out an annual questionnaire). It turned out that they had not though, interestingly, I understand that they do ask a question about this when surveying participants in the IBIS2 follow-up study testing Anastrozole, an alternative to Tamoxifen.

Eventually we were invited to meet a Professor who was one of those leading these trials. He was a very personable guy who thought S's mum might have been one of his early patients. I raised some of the things that perplexed me about the drug and its possible effects and he, very charmingly, answered them - up to a point though the answer often amounted to 'we don't really know'.

In a follow-up post I will summarise the letter he sent us following our meeting, when I have unearthed it from my increasingly chaotic 'filing system'.

Now I must go and wake S up as, for the second day running, she has slept well past noon.

At least, one way or another, she has so far avoided breast cancer. There's always a bright side if you look hard enough.