Stress Hormone Therapy Used To Treat Breast Cancer Side Effects May Make Tumors Drug Resistant

Breast Cancer Hormone Therapy
Hormone therapy for breast cancer treatment side effects may be undoing treatment. Photo courtesy of Shutterstock

Hormones play a pivotal role in breast cancer from diagnosis to treatment, and balancing their use to make sure the good side effects outweigh the bad can get tricky. For example, researchers from the Thomas Jefferson University recently disocvered that the stress hormones doctors currently use to treat side effects of breast cancer therapy, could actually be making tumors treatment-resistant. Their findings were published in the journal Oncogene.

Up to 80 percent of all invasive breast cancer cases are driven by the hormone estrogen; these cases are diagnosed as estrogen receptor (ER) positive disease. Women with ER positive disease are treated with estrogen blockers, such as tamoxifen or aromatase inhibitors to starve the cancer cells, eventually stopping the growth of cancer. However, after 10 years about 25 percent of patients will develop resistance to the drugs.

The researchers believe drug resistance is caused by CK5 cells because they have the ability to reject estrogen-blocking therapy and chemotherapy. About 10 to 15 percent of ER positive disease patients have CK5 cells within their breast cancer tumor already. Overtime the tumor accumulates CK5 cells and eventually begins rejecting therapy treatments.

Previous research shows the hormone progesterone stimulates the growth of CK5 cells in breast cancer. Progesterone is an ingredient found in birth control and hormone replacement therapies for menopausal women, and naturally produced when the body is under stress.

Progesterone belongs to a family of hormones called 3-ketosteroids, which include glucocorticoids used to treat nausea and other symptoms of breast cancer therapy treatments. The researchers suspected since progesterone causes CK5 cell growth, perhaps other stress hormones within the same family could also be causing problems. When they tested out four other steroids from the 3-ketosteroids family, not only did glucocorticoid boost CK5 cell growth, but so did two of the other steroids dexamethasone and aldosterone by as much as four to seven times. The experiment was repeated in mice with human breast cancer tissue cells with the same results.

"Not only are these steroids sometimes used in cancer treatment, glucocorticoid hormones are also naturally produced by the body in response to stress," the study’s co-author Chelain Goodman, a medical student at Thomas Jefferson University, said in a press release. "Women with breast cancer experience greater levels of stress and studies have shown that this stress can negatively impact their treatment.”

In order to stop stress hormones from growing CK5 cells, researchers used the hormone prolactin, which naturally triggers women to produce milk after childbirth. Prolactin also helps maintain mature healthy breast cells. But because CK5 cells are immature, it was able to stunt their growth and ultimately counteract stress hormones’ negative effects.

"The data we have collected suggests that hormones used in breast cancer treatment, which are also produced by the body in response to stress, could have a major impact on disease progression and outcomes in some patients," the study’s senior author Dr. Hallgeir Rui, a cancer professor at Thomas Jefferson University, said in a press release. "Although prolactin appears to be an excellent candidate to counteract the effect of stress hormones on women with this subtype of breast cancer, the hormone can also drive other types of breast cancer, so we must proceed with caution."

Source: Rui H and Goodman C. Oncogene. 2015.

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