Study Suggests Chemo Before Surgery May Promote Metastasis

In most cases, chemotherapy is a helpful and even lifesaving technology that slows the growth of cancer and sometimes even eliminates it altogether. But in certain situations, it also has the potential to exacerbate the issue.

Chemotherapy as a neoadjuvant therapy (a treatment given before surgery) was initially only used on larger tumors, but as breast cancer education flourished and tumors began to be caught when they were smaller, doctors began to use chemotherapy on smaller tumors in the hopes of increasing the chances and length of time of survival.

This may not be the best idea for certain cases, however. According to studies done with lab mice and human tissues, receiving chemotherapy to shrink a tumor before a surgery can actually cause the cancer to metastasize to other areas of the body, making it potentially incurable.

The reason appears to be that there are certain “on-ramps” to the body’s blood vessels that are affected by typical chemotherapy drugs like paclitaxel, doxorubicin, and cyclophosphamide. When an immune cell meets a tumor cell near one of these “on-ramps,” it allows it access into the blood vessel, which will carry it to other parts of the body where it can metastasize into a new tumor.

Photo: Adobe Stock/JPC-PROD
Photo: Adobe Stock/JPC-PROD

A 2014 study of 3,760 patients revealed that the risk level for this metastasis is based on the patient’s individual “tumor microenvironment,” which refers to the number of tumor cells, immune cells, and blood vessel cells (the “on-ramps”) that are touching each other.

In this study, researchers looked at 20 breast cancer patients who underwent pre-op chemotherapy and investigated their tumor microenvironments before and after chemo. None of the patients saw an improvement in their tumor microenvironments, and many saw increased risk of metastasis after treatment. Paclitaxel was shown to increase cancer cell mobility, make blood vessels more permeable to cancer cells, and increase the number of immune cells ushering cancer cells onto the “on-ramps.” Doxorubicin and cyclophosphamide had a similar effect.

The lesson here is that if the tumor is small enough for a simple lumpectomy without neoadjuvant chemotherapy, that may be the best option to avoid the extra risk of metastasis. Julio Aguirre-Ghiso of Mount Sinai School of Medicine, an expert in metastasis who was not involved in the study, says the study is a reminder that our scientific advancements do sometimes have downsides.

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“It raises awareness that we might have to be smarter about how we use chemotherapy.”

So while breast cancer death rates continue to drop thanks to scientific advancements like chemotherapy, it is important to remain aware that there is still work to be done.

Critics of the study believe that if chemo really increased the chances of metastasis, it would have shown up in studies before now. More specific future research should give us more insight into exactly how risky neoadjuvant chemotherapy actually is and provide less problematic options for shrinking tumors before surgery.

Photo: Adobe Stock/Monkey Business
Photo: Adobe Stock/Monkey Business

If chemotherapy and surgery are likely in your future, talk to your oncologist about the potential risks and benefits of neoadjuvant chemotherapy. A simple lab test may be able to determine how much effect chemotherapy will have on your tumor microenvironment and your cancer’s ability to metastasize.

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