A study in mice sheds light on the mechanisms through which stress can contribute to the spread of breast cancer.
Breast cancer is one of the most common types of cancer.
In the United States, there were about 266,120 new cases last year, according to the National Cancer Institute.
Although breast cancer is also one of the most treatable types of cancer, once it metastasizes — that is, grows and spreads — it can be quick to diversify.
When cancer tumors are so diverse, doctors may find it hard to apply the right kind of treatment, as the therapy that works for one type of tumor may have no effect on another.
Previous research that Medical News Today covered suggests that exposure to chronic (long-term) stress is one factor that contributes to cancer cell growth in breast cancer.
Now, a new study conducted by a team from the University of Basel and the University Hospital of Basel in Switzerland has uncovered further evidence to suggest that stress can fuel the spread of breast cancer tumors, perhaps also supporting their diversification.
The study — which the team carried out in a mouse model — found that stress hormones support breast cancer metastasis. The scientists also state that the stress hormone derivatives present in certain anti-inflammatory treatments could actually “disarm” chemotherapy agents.
Lead author Prof. Mohamed Bentires-Alj and colleagues explain their findings in a new study paper that appears in the journal Nature.
“Intra-patient tumor heterogeneity is an obstacle to treatment,” they note, “as it causes divergence in diagnostic markers between primary tumors and matched metastases that may lead to inadequate treatment.” They say that new research needs to find a way to address this mismatch.
The intricate mechanisms at play
Prof. Bentires-Alj and team worked with a mouse model of breast cancer. They started by studying how different the original tumors were from metastatic tumors by assessing specific gene activity.
The researchers note that in metastatic tumors, a type of receptor called “glucocorticoid receptors” were very active. These receptors bind to stress hormones, including cortisol.
Also, the team found that mice with metastases had higher levels of cortisol and another stress hormone, corticosterone, than rodents in which cancer had not yet spread.
The investigators also observed that when these stress hormones are highly present, they activate glucocorticoid receptors. This, they explain, triggers cancer cells’ spread and supports their diversification.
Furthermore, Prof. Bentires-Alj and colleagues saw that glucocorticoid receptors also interact with synthetic derivatives of cortisol — for example, dexamethasone — which doctors use as anti-inflammatories to address some of chemotherapy’s side effects.
This interaction, however, seems to interfere with some chemotherapeutic agents, neutralizing their effects. This is what happens with the chemotherapy drug paclitaxel, for instance; it becomes less effective in the presence of dexamethasone.
Based on these results, the scientists advise physicians to use caution in prescribing glucocorticoid hormones for the treatment of breast cancer, in case they end up doing more harm than good.
Prof. Bentires-Alj and team also explain that by the same token, inhibiting glucocorticoid receptors could be a helpful new approach in breast cancer treatment. “Tumor heterogeneity is a serious hurdle for therapy,” explains Prof. Bentires-Alj.
“These findings highlight the importance of stress management in patients — and especially those with triple-negative breast cancer. Moderate exercise and relaxation techniques have been shown to correlate with enhanced quality of life and greater survival in patients.”
Prof. Mohamed Bentires-Alj