The Vicious Cycle: Stress and Cancer

by PJ Hamel Patient Expert

Many of us who've had breast cancer have noticed that its diagnosis was preceded by a period of emotional stress. And certain scientific studies have borne out this connection. Now, scientists have made a tentative link between stress and breast cancer metastasis - and by association, death.

The six months before my breast cancer diagnosis were some of the hardest of my life. Family issues and an ever-increasing workload combined to make each day a minefield of problems. I remember thinking, "The only way I'm going to get a break here is to wind up in the hospital."

Which I did, shortly thereafter. I spent 9 months in and out of the hospital undergoing breast cancer treatment.

A friend of mine, after years enduring a difficult career, finally decided to call it quits; a month later, she was diagnosed with breast cancer. Another friend got the cancer news just months after a painful, drawn out, extremely acrimonious divorce.

As it turns out, this isn't just simple coincidence. Certain studies over the years have drawn a connection between stress - which compromises the immune system's ability to respond - and cancer diagnosis.

Now, a study published in the Journal of Clinical Investigation in August, 2013 shows another connection: between stress and breast cancer metastasis. Since metastasis ultimately leads to death, the inference can be drawn that stress can be a factor in whether you survive breast cancer - or not.

The study identifies a gene, ATF3 ("the stress gene"), that appears to turn cancer-fighting immune cells into "cancer helpers" - cells that actually allow cancer to escape from its original tumor and travel to distant places in the body.

ATF is activated when the body is exposed to stress. ATF causes cells that have been damaged by stress to "commit suicide" - to die, so that their damage isn't passed along to new cells.

When cancer first develops, the body sends immune cells to the site of the errant cancer cells; the immune cells attack and destroy the cancer. However, in some cases, those cancer cells turn the table on the immune cells: they manage to activate the ATF3 gene in those immune cells, causing the cells to malfunction. The result? Cancer cells escape the tumor site without resistance, and travel to other parts of the body.

What causes the stress gene to become active? First, ATF3 is activated by both cancer cells, and cancer treatment itself (radiation, chemotherapy). But it's also kicked into gear by other, non-cancer conditions: UV damage to the skin, for instance (high levels of ultraviolet light); a high-fat diet, and chronic behavioral stress. (Paddock, 2013)

So if the stress gene is activated by cancer and cancer treatment, why don't all of us with cancer see it spread?

Because we all react differently to the factors that activate ATF3. Some of us produce more of it than others; and the more ATF produced, the greater the danger of metastasis.

The study's senior author, Dr. Tsonwin Hai of Ohio State University, and colleagues were able to determine that ATF3 activation produces certain "gene signatures;" ATF3 expresses ATF3 protein, which can turn other genes on and off. Depending on exactly which other genes are turned on (or off), researchers were able to connect certain gene signatures with a high (or low) risk of dying from cancer. Thus, in the future oncologists may be able to administer a test that predicts risk of metastasis, just as the Oncotype-DX test today predicts effectiveness of chemotherapy based on gene signatures.

All of this research is still very preliminary, and years from being translated into a possible drug intervention to control ATF3. But one thing seems increasingly clear: stress and cancer go hand in hand.

Certainly not every woman who's stressed develops breast cancer. But if other factors are in place - environmental, lifestyle, and/or genetic - stress could very well be the X factor that causes cancer to begin. And not just to begin, but to spread" and kill.


Paddock, C. (2013, August 27). Stress fuels cancer spread by triggering master gene. Retrieved from

How our own bodies help turn cancer against us. (2013, August 26). Retrieved from

PJ Hamel
Meet Our Writer
PJ Hamel

PJ Hamel is senior digital content editor and food writer at King Arthur Flour, and a James Beard award-winning author. A 16-year breast cancer survivor, her passion is helping women through this devastating disease. She manages a large and active online survivor support network based at her local hospital and shares her wisdom and experience with the greater community via