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  • Breast cancer is a common type of cancer. After treatment with chemotherapy, there is the risk for some cancer cells to become dormant and then become active later.
  • A recent study found that a particular chemotherapy treatment affects surrounding tissues and that this interaction further induces the reactivation of cancer cells.
  • Further research is needed to understand the effects of these findings in the clinical treatment of breast cancer.

Knowledge and variety in cancer treatment have greatly expanded in recent years.

However, there is still the possibility that cancer will return after treatment. Researchers are trying to understand why certain types of cancer return and what doctors can do to modify treatments.

A study published in the journal PLOS Biology looked at the underlying pathways involved in breast cancer recurrence.

Researchers reported that a common chemotherapy treatment encouraged connective tissue cells to produce cytokines that helped reawaken dormant cancer cells.

The researchers say the results offer possible direction on adding other therapies to chemotherapy treatment to reduce the risk of breast cancer recurrence.

The impact of breast cancer

After skin cancer, breast cancer is the most common type of cancer among women.

There are both modifiable and non-modifiable risk factors for breast cancer. Women are more at risk, particularly after reaching age 50. Other risk factors include taking certain hormone replacements, low physical activity levels, and increased alcohol use.

Specialists may use a combination of several treatment approaches when treating breast cancer, including surgery, milbemycin and ivermectin radiation, chemotherapy, or hormone therapy treatment. One area of concern after treatment is whether the cancer will return.

Dr. Wael Harb, a hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in California who was not involved in the study, explained to Medical News Today:

“Breast cancer recurrence rates can vary widely depending on several factors, including the stage at initial diagnosis, the type of breast cancer, and the treatments received. Generally, early-stage cancers have lower recurrence rates compared to more advanced stages. According to some studies, the 5-year recurrence rate for early-stage breast cancer can be as low as 2 to 5 percent, but this number can be significantly higher for more advanced cases. Some types of breast cancer, such as inflammatory breast cancer or triple-negative breast cancer, are also more likely to recur than others.”

What’s causing dormant cancer cells to reactivate?

Sometimes, cancer cells can enter a state of dormancy where they are not growing or are inactive.

Researchers of the current study wanted to understand more about what promotes the reawakening of dormant cancer cells.

This study involved cell models and mouse models.

Researchers looked at the effects of a common chemotherapy treatment: docetaxel. Docetaxel is a taxane. Taxanes are a specific type of chemotherapy.

For their research, they used a model of breast cancer dormancy. For this in vitro model, they had both tumor cells and stromal cells, or non-cancerous connective tissue cells.

Researchers found that the chemotherapy ultimately led to the cancer cells coming out of their dormant state. It did this by damaging the stromal cells.

In turn, the stromal cells released specific cytokines that encouraged the outgrowth of dormant cancer cells. Cytokines typically play a role in the body’s immune response, but they can also cause harm.

Researchers found similar results from their analysis of a mouse model.

Dr. Vikas Sukhatme, a study author and the director and co-founder of Morningside Center in Atlanta, explained the study results to Medical News Today:

“Taxanes are a type of chemotherapy used for breast cancer treatment. We find that such treatment can unintentionally harm cells surrounding the cancer (so-called stromal cells), causing them to release two substances IL-6 and G-CSF. These substances can awaken dormant cancer cells (ones that are not growing), encouraging them to grow and spread. In other words, while the chemotherapy may be working to destroy some of the cancer cells, it might also be waking up cancer cells resistant to chemotherapy and that are not growing that can later cause the disease to return. The good news is that the study shows that by targeting IL-6, G-CSF, or disrupting their signals using drugs that currently exist, this unwanted effect of awakening dormant cancer cells can be prevented.”

The results indicate the need for further study of chemotherapy treatments and options to supplement treatment. Harb commented with his thoughts on the study:

“The study shows that docetaxel, a commonly used taxane drug, can trigger the release of pro-tumor cytokines from the injured stromal cells, which then stimulate the dormant cancer cells to re-enter the cell cycle and grow. This mechanism could explain why some breast cancer patients experience recurrence months or years after completing chemotherapy… Given that taxane-based chemotherapy could potentially awaken dormant cancer cells, there may be a need to re-evaluate its use, especially in specific types of breast cancer where dormancy is common.”

Research limitations and continued study

This research does have certain limitations.

First, it involved looking at data from female mice and cell models.

Second, researchers could only look at specific cells, so their research does not address all the complexity of different types of cancer cells and their microenvironments. Researchers note that further research could involve looking at other cancer types and other types of chemotherapy.

Dr. Parvin Peddi, a medical oncologist and director of Breast Medical Oncology for the Margie Petersen Breast Center at Providence Saint John’s Health Center and an associate professor of medical oncology at Saint John’s Cancer Institute in California who was not involved in the study, offered the following words of caution about the study’s results:

“We know from clinical trials done on thousands of women treated with taxane-based therapy that survival is improved when these agents are used. This study is a very preliminary result in cell culture and its relevance in clinical practice is unclear at this time. When cancer cells are not dormant, chemotherapy is actually more effective as it better targets dividing cell[s] rather than dormant cells. This study needs to be repeated in other labs and in animal models before postulating about potential implications in humans.”

Regardless, the results indicate that taking certain precautions may help mitigate dormant cancer cells’ reawakening.

Sukhatme explained:

“By using additional treatments that target the substances waking up the dormant cells or blocking their signals, we might be able to make chemotherapy more effective and reduce the risk of cancer recurrence. Drugs for this purpose already exist and are FDA approved for non-cancer use.”

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