Stress Hormones May Reduce Breast Cancer Treatment Efficacy

Hormones that reduce side effects may stimulate growth of cells resistant to therapy.

Hormones administered to breast cancer patients to reduce side effects may actually reduce the efficacy of treatments for the disease.

A study published recently in the journal Oncogene evaluated the hormone progesterone, an ingredient in contraceptives and menopausal hormone replacement therapies, which may stimulate the growth of breast cancer cells resistant to anti-estrogen therapy and chemotherapy.

The researchers found that stress hormones frequently used to treat the side effects of common chemotherapy could cause cancer drugs to fail sooner in some breast cancer patients, however this effect may be reversible.

"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," Hallgeir Rui, MD, PhD, said in a press release. "However, these studies must be confirmed in clinical trials with patients before any new treatment recommendations can be made."

Approximately 70 to 80% of invasive breast cancers are driven by estrogen, which is called estrogen receptor (ER) positive disease. Patients are able to successfully limit the growth of cancer with therapies that block estrogen receptors.

Some women can use hormone blockers such as tamoxifen or aromatase inhibitors to manage the cancer for a decade or more, however, 1 in 4 women develop resistance. The study noted that CK5 cancer cells are able to resist estrogen-blocking therapy and chemotherapy.

The researchers exposed breast cancer cell lines to four 3-ketosteroids, 2 of which, dexamethasone and aldosterone, increased CK5-cell numbers as much as 4 to 7 times. Human breast cancer cells grown in mice showed increased growth of therapy-resistant tumors in mice treated with dexamethasone and aldosterone.

"Not only are these steroids sometimes used in cancer treatment, glucocorticoid hormones are also naturally produced by the body in response to stress," first author Chelain Goodman, MD, PhD 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. Glucocorticoids are also widely prescribed for common diseases, including many chronic rheumatoid or autoimmune diseases which can co-occur with breast cancer. This research helps pinpoint a new mechanism behind therapy-resistance in patients with this subtype of ER-positive breast cancer containing CK5 cells and suggests a way to counteract the effect.”

To counteract the effect of stress hormones, the researchers used prolactin, which is able to maintain cell maturity. CK5 cells are less mature and similar to stem cells, according to the study. As a result, when prolactin was added to cells exposed to 3-ketosteroids, CK5 cells were prevented from expanding.

"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. An alternative possibility supported by this research is inhibiting a protein called BCL6 that appears to be critical for steroid-induction of CK5 cells,” Dr. Rui said. "Perhaps the simplest solution would be to seek alternatives to steroids for controlling the side-effects of chemotherapy in patients with this tumor subtype."