Recurrence Rollercoaster – #1 – Why Tamoxifen didn’t work for me


So, for newcomers, a quick recap of the back story:  I had a mastectomy, and when I woke up from surgery, discovered my left arm was paralysed.  This had been caused by damage to the brachial plexus nerve that controls the arm.  I had to have further surgery to free the injured nerves.

It took about nine months before I was finally able to lift my left arm, and control it.  It was a dark time, and I remember being in a state of numbness most of the time.  I still look back on that period with a sense of incredulity, and amazement that I got through it.

In those nine months, to give my arm the best chance of healing, my surgeon and I took the decision not to have any active treatment in case they damaged the nerves.  I was also hoping that the treatments I’d had at Hallwang Private Oncology Clinic in Germany would help.


I agreed that I would go on Tamoxifen.  This was a big deal for me as I’d been so anti-chemicals and hormonal treatments because of their side-effects.  Plus, my track record with conventional treatment (i.e. the paralysis caused by the mastectomy) wasn’t brilliant.  But by then I was starting to panic and wondering what I could do to keep the cancer away.  Never mind that taking Tamoxifen also increased the chances of getting premature menopause, hot flashes, endometrial cancer, deep vein thrombosis, pulmonary embolisms.  Better than dying of cancer, right?

I didn’t have the money to go to Germany for treatments, and also I couldn’t travel by myself because of the paralysed left arm.

Whether staying away from active treatment was a good decision is moot, because about ten months after the mastectomy, I felt a few tiny bumps under my armpit, and a few on the scar line.  I think I was in denial.  Because when I saw the breast surgeon, he said they felt like “disease”.  This was his way of referring to cancer.

[Interestingly, when I was at Hallwang, I was told that the effects of their tri-functional antibody treatment, Removab, would last approximately nine months.  And my recurrence was just after the nine-month period.  So I guess I bought myself some time if indeed it was Removab working.]


“But … but … I’m on Tamoxifen!!!”

Well, it was obvious the Tamoxifen wasn’t working, and the only reason I found out was through the help of Grace Gawler, a cancer strategist.  She told me that a few of her clients had had issues with Tamoxifen, and advised that I get a test called the Cytochrome P450 2D6 Genotype for Tamoxifen Hormonal Therapy (“CYP2D6 test)

Even my breast surgeon had not heard of this test, but it was used in the US and in Australia (where Grace is based).

What the CYP2D6 test could show was whether or not I was metabolising Tamoxifen properly – the thing about Tamoxifen is that it has to be broken down by the liver using the CYP2D6 enzyme, into the active ingredient, Endoxifen.  And in order to do that, the person needs two parts (alleles) of a specific gene, the Cytochrome P450.

“The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, and is one of the main enzymes responsible for converting tamoxifen into its major active metabolite, endofixen.

Variants in the CYP2D6 allele may lead to reduced (“intermediate metabolizer”) or absent (“poor metabolizer”) enzyme activity.

Individuals who carry these variant alleles may have reduced plasma concentrations of endoxifen and benefit less from tamoxifen therapy.”  Source:

It was a bit of a palaver getting the test.  My research showed there were only two labs who offered this test:

1.  Mayo Clinic Medical Laboratories:

Test ID: 2D6TO
Cytochrome P450 2D6 Genotype for Tamoxifen Hormonal Therapy, Saliva

329642D6 Tamoxifen Genotype Interp

329652D6 Tamoxifen Reviewed by

329662D6 Tamoxifen Phenotype Interp

2.  Roche  – AmpliChip®CYP450 Test

We got the test done by Roche and true enough, it showed that I was an intermediate metaboliser (I only had one allele of the gene expression), which put simply meant that I wasn’t able to break down the tamoxifen efficiently and not enough of it was in my body to be useful.

So the solution was to increase the dose of tamoxifen from 20mg to 40mg.  There is research to show that increasing the dose of tamoxifen may be effective for poor to intermediate metabolisers:

“It follows that at least one functional or partially functional allele, in the case of Intermediate Metabolisers (IM), is necessary to reach endoxifen levels that are not statistically different from Eeffective Metabolisers (EM) upon dose adjustment.

Supportive evidence came from another study that increased tamoxifen dose from 20 to 30 mg/day in patients with baseline endoxifen levels below 40 nmol/l. An increase to clinically meaningful endoxifen concentrations was observed; however, this was dependent on CYP2D6 genotype, with PMs having lower rates of increase.

Moreover, after tamoxifen dose adjustments to 30 or 40 mg/day based on CYP2D6 genotype, Japanese patients with one copy of reduced functional allele reached endoxifen levels comparable with the patients with two functional alleles.

Collectively, these studies suggest thatCYP2D6 molecular diagnostics could play an important role in the case of planned tamoxifen dose adjustment in patients with moderately impaired metabolizer statuses such as IM or heterozygous EM patients.”


So, if you’re reading this, you may be wondering: why don’t they test all breast cancer patients for this CYP2D6 gene thingy, before administering Tamoxifen?  Well, it’s expensive and not covered by the NHS.   I was lucky to have private medical insurance and a persuasive breast surgeon who was eager to get to the bottom of things.  And also fortunate to have the knowledge and experience of someone who’d seen it all before: Grace Gawler.

Another reason why this CYP2D test is not widely-used is because it is controversial.  There are studies that show that the test is flawed, and not accurate.

Recent research seems to show that the test may be effective:

“Despite clinical recommendations against using Cytochrome P450 2D6 (CYP2D6) gene expression as a guide for tamoxifen therapy for breast cancer patients, a study from the Mayo Clinic suggests otherwise.

The laboratory of Matthew Goetz, MD, writing in the journal article “Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Germline Pharmacogenetic Studies,” published in Journal of the National Cancer Institute, suggests that the trials on which the recommendations were based were prone to error.”

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