Key messages

• We are not sure whether tamoxifen benefits survival, disease progression (disease getting worse), or well-being in people with advanced hepatocellular carcinoma (the most common type of liver cancer) when compared with no active treatment, supportive treatment (to relieve symptoms), or a dummy pill.

• We are not sure whether tamoxifen changes how often serious and non-serious unwanted effects occur in people with advanced hepatocellular carcinoma (where the cancer has spread) when compared with no active treatment, supportive treatment, or a dummy pill.

What are hepatocellular carcinoma and tamoxifen?

Hepatocellular carcinoma is a common primary liver cancer in adults. This means the cancer cells started in the liver. It occurs most often in people infected with hepatitis B or C viruses for a long time. Hepatitis B and C are liver infections.

Hepatocellular carcinoma can be diagnosed by scanning the liver with a detector and a high level of a tumour marker, called alpha-fetoprotein, in the blood. If the results of the scan are unclear, a liver biopsy can be performed. Liver biopsy is a procedure in which a needle is inserted into the liver and a tiny piece of liver tissue is taken for analysis under a microscope.

Hepatocellular carcinoma is usually treated with surgery, medicines to kill the cancer cells given locally (directly into a blood vessel supplying the cancer), or a liver transplant. In advanced cases (where the cancer has spread), supportive care is provided to relieve symptoms.

Tamoxifen is a medicine that decreases the effects of oestrogen. Oestrogen is a hormone responsible for female sex characteristics that is found in both women and men. Tamoxifen prevents oestrogen from interacting with cancer cells and may reduce the growth and spread of cancer.

What did we want to find out?

We wanted to find out if tamoxifen was better than no treatment, supportive treatment, or a dummy pill to reduce death, improve well-being, and slow down the worsening of the disease. We also wanted to find out if tamoxifen was associated with any serious (life-threatening) or non-serious unwanted effects.

What did we do?

We searched for studies that compared tamoxifen with a control group consisting of no treatment, supportive treatment, or a dummy pill. We compared and summarised the results and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found 10 studies that included 1715 people with inoperable (cannot be removed using surgery) or advanced (late-stage) hepatocellular carcinoma. All studies assessed tamoxifen given by mouth. The largest study included 496 people, and the smallest study included 22 people. Six studies were conducted in one centre, three studies were performed in multiple centres in one country, and one study was performed in multiple centres across nine countries. Pharmaceutical companies, national research grants, and local institutional grants funded these studies. All 10 studies had problems with design and methods.

There was little to no difference in the number of deaths between the tamoxifen group and the control group after monitoring for one to five years (eight studies). In the tamoxifen group, 488 of 682 people (72%) died compared to 487 of 682 people (71%) in the control group.

The evidence is very uncertain about the effect of tamoxifen and control on serious unwanted effects. Only one study reported serious unwanted effects at the end of one year.

The evidence is very uncertain about the effect of tamoxifen and control on the well-being of people after monitoring for nine months (one study).

There was little to no difference in the worsening of the disease between the tamoxifen group and the control group after monitoring for one to five years (four studies). In the tamoxifen group, 191 of 359 people (53%) had cancer progression compared to 198 of 362 people (55%) in the control group.

Tamoxifen may have little to no effect on unwanted events considered non-serious after monitoring for one to three years, but the evidence is very uncertain (four studies). In the tamoxifen group, 10 of 265 people (4%) had non-serious unwanted effects compared to 6 of 197 people (3%) in the control group.

What are the limitations of the evidence?

Our confidence in the evidence is low to very low because of the small number of studies with few participants. Some of the studies did not report their methods. It is possible that people in the studies were aware of which treatment they received. Not all the studies provided data about everything that we were interested in. Poor study methods could exaggerate or underestimate the benefits and unwanted effects of tamoxifen. We still lack evidence on the effect of tamoxifen compared with no treatment, supportive treatment, or a dummy pill on death, well-being, worsening of cancer, and serious and non-serious unwanted effects.

How up to date is this evidence?

The evidence is up to date to 26 March 2024.