Hormone drugs in breast cancer treatment put some cancer cells to 'sleep', allowing them to wake up later and the cancer to return

The 'sleeper cells' could provide clues as to why some breast cancer cells become resistant to treatment, causing a patient's drugs to stop working, and their cancer to return, says the team


                            Hormone drugs in breast cancer treatment put some cancer cells to 'sleep', allowing them to wake up later and the cancer to return

The medicine that is given to treat breast cancer could be forcing some cancer cells into a "sleeper" or inactive mode, allowing them to come back to life years after the initial treatment.

Scientists at Imperial College London, who studied a group of breast cancer drugs called hormone treatments, say the findings are crucial as about 30% of breast cancer patients taking hormone therapies see their cancer eventually return, sometimes 20 years after treatment.

The returning cancer is usually metastatic, which implies that it has spread around the body, and the tumors are often resistant to medication, says the team.

The early-stage discovery, published in the journal Nature Communications, opens avenues to figure out ways of keeping the cancer cells dormant for longer, or even potentially finding a way of awakening the cells so they can then be killed by the treatment, according to the research team.

"For a long time, scientists have debated whether hormone therapies — which are a very effective treatment and save millions of lives — work by killing breast cancer cells or whether the drugs flip them into a dormant 'sleeper' state. This is an important question as hormone treatments are used on the majority of breast cancers. Our findings suggest the drugs may actually kill some cells and switch others into this sleeper state," says Dr. Luca Magnani, lead author of the study from Imperial's Department of Surgery and Cancer.

Magnani adds, "If we can unlock the secrets of these dormant cells, we may be able to find a way of preventing cancer coming back, either by holding the cells in permanent sleep mode or be waking them up and killing them."

Hormone therapies are used to treat a type of breast cancer called estrogen-receptor positive. These make up over 70% of all breast cancers and are fuelled by the hormone estrogen. According to researchers, these cancers are usually treated with surgery to remove the tumor, followed by a course of targeted hormone therapy — usually either aromatase inhibitors or tamoxifen, which target estrogen receptors.

"Although treatments for breast cancer are usually successful, cancer returns for some women, often bringing with it a poorer prognosis. Figuring out why breast cancer sometimes comes back is essential to help us develop better treatments and prevent this from happening," says Dr. Rachel Shaw from Cancer Research UK.

She adds, "This study highlights a key route researchers can now explore to tackle 'sleeping' cancer cells that can wake up years after treatment, which could potentially save the lives of many more women with the disease."

For the current research, the team studied around 50,000 human breast cancer single cells in the lab and found that treating them with hormone treatment exposed a small proportion of them as being in a dormant state. The researchers say the "sleeper cells" may also provide clues as to why some breast cancer cells become resistant to treatment, causing a patient's drugs to stop working, and their cancer to return. 

Breast cancer sleeper cells: Dormant 'sleeper' cells (red) and active cancer cells (green). (Luca Magnani et al. Nature Communications 2019)

The researchers explain that the sleeper cells appear to be an "intermediate stage" to the cells becoming resistant to the cancer drugs. The findings also suggest that the drugs actually trigger the cancer cells to enter this sleeper state, according to the team. 

The analysis shows that cells in this dormant sleeper state are more likely to spread around the body. "Our experiments suggest that these sleeper cells are more likely to travel around the body. They could then 'awaken' in other organs of the body, and cause secondary cancers. However, we still don't know how these cells switch themselves into sleep mode — and what would cause them to wake up. These are questions that need to be addressed with further research," says Dr. Sung Pil Hong, study co-author from Imperial.

According to researchers, since hormone therapies remain one of the most effective treatments against breast cancer, further patient research will focus on whether taking hormone therapies for longer after initial cancer treatment could prevent the cancer cells from waking from their sleeping state.

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