Simple anti-inflammatory medication may prolong effect of breastcancer treatment

Researchers from the Netherlands Cancer Institute, Oncode Institute and the University of Genoa have now uncovered a way that could make hormone therapy work for a longer period through the use of an existing, safe and inexpensive type of medicine: corticosteroids. They publish their findings today in the leading journal Nature and will soon launch a study for patients with metastatic breast cancer. 
More than 3,000 women in the Netherlands pass away because of breast cancer each year. Most women with this disease are diagnosed with hormone-dependent cancer and receive hormone therapy to block tumor growth. This treatment can suppress the disease for years, but resistance often occurs and the tumor can regrow despite therapy, requiring more intensive treatments.

Recent research by Irene Caffa and Alessio Nencioni at the University of Genoa and San Martino Hospital suggests that patients who follow a specific low-calorie diet may respond better to hormone therapy, which might delay the necessity to switch to more intensive treatments, such as chemotherapy. The idea of modified diets to improve cancer treatment is appealing, but due to the low amount of calories ingested per day (sometimes as little as 300 to 600), it is incredibly hard for people to follow such a diet, especially when they are ill. Not to mention the associated risks of malnutrition. Patients who follow this kind of diet as part of clinical studies do so only under close medical guidance.
The Italian study immediately caught the attention of Nuno Padrão , PhD candidate at the Netherlands Cancer Institute. He was determined to find out how this diet aids sensitivity to hormone therapy, as there was no conclusive underlying biological explanation. Nuno: “My grandmother was diagnosed with breast cancer a few years earlier, and I realized how hard it would have been for her to follow such an extreme diet. It would be great if we could help patients like her in a more feasible way.”

He convinced his group leader Wilbert Zwart, contacted the Italian team, and initiated a joint investigation. Through a clever combination of experiments in cells, mice and patient samples, the researchers discovered that cortisol plays a key role. This hormone is produced when the body is under physical or psychological stress, including times of very low calorie intake.
“We witnessed cortisol levels rise sharply in the blood of patients and mice when they consumed very few calories,” Zwart recalls. “This hormone can enter tumor cells and slow their growth. When we modified cancer cells to no longer respond to cortisol, the positive effect of the diet on the response to hormone therapy disappeared. That’s when I knew we were onto something big.”

Follow-up studies confirmed the crucial role of cortisol, which is part of the corticosteroid family. Treatment with these drugs reactivated the sensitivity to hormone therapy in mice: it made the tumor ‘believe’ that the body was following a strict diet, without actually reducing calorie intake.
The best part: physicians have been using corticosteroids as anti-inflammatory drugs for years to treat conditions like chronic inflammation and asthma, which means that there is extensive medical experience with these drugs. Zwart says: “These findings suggest that we may have uncovered a new application for this widely used and inexpensive medication, which may be able to replace or delay more intensive, expensive treatments.”

Because the NKI houses a hospital and research institute under one roof, Zwart was able to immediately involve his clinical colleagues. Together, they were able to translate the discovery into a clinical trial that is set to open next year, with the support from Oncode Institute. Patients with metastatic, hormone receptor-positive breast cancer will be treated with corticosteroids alongside hormone therapy (see below).
“It would be highly beneficial for these patients if we can demonstrate that we can safely postpone the need to prescribe chemotherapy by restoring sensitivity to hormone therapy,” says Vincent Dezentjé, the medical oncologist who will lead the study. He treats people with breast cancer and conducts research on hormone therapy. “These patients have metastatic cancer, will likely succumb to the consequences of the disease, and are heavily affected by intensive treatments such as chemotherapy. It would be incredibly valuable if a corticosteroid would allow them to continue benefitting from a milder treatment like hormone therapy. Ideally, this would also help them live longer with a better quality of life.”

The research at the Netherlands Cancer Institute is financially supported by KWF Dutch Cancer Society and the Antoni van Leeuwenhoek Foundation. The group led by Wilbert Zwart receives additional funding through Oncode Institute.