Researchers have achieved improved, long-term control of drug-resistant breast cancer growth in mice with the use of oestrogen and anti-oestrogen treatments.
A team of researchers at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) have found that switching between oestrogen and anti-oestrogen treatment at a specific point in time can significantly increase the duration of tumour regression in mice. A clinical trial will now be carried out to inform which breast cancer patients may benefit from this treatment.
The findings have been publishing in Oncogene.
Oestrogen treatment and anti-oestrogen treatment
Anti-oestrogen treatments block growth signals from oestrogen receptors (ER) in tumours. These treatments have been found to be effective for ER-positive breast cancer, however, it can be common for the tumours to become resistant to anti-oestrogen treatments over time.
For the research, the team, led by molecular biologist Todd Miller, PhD, and Nicole Traphagen, a PhD candidate in the Miller Laboratory, took an unconventional approach which suggests that treating patients short-term with oestrogen before anti-oestrogen therapy resistance occurs, and then switching back to anti-oestrogen therapy can offer better control of tumour growth. An ongoing clinical trial at NCCC will now determine whether the strategy of cycling between the two therapies is effective in human patients with advanced breast cancer.
Miller noted that oestrogen treatment is effective in some patients, however, this form of therapy is rarely used: “Although we typically think of oestrogens as feeding breast cancer growth, treatment with oestrogens can actually induce tumour regression in some patients with anti-oestrogen resistant breast tumours.”
“Tumours that initially respond to oestrogen therapy eventually develop resistance to it by decreasing the amount of oestrogen receptors in the tumour cells. Once these tumours become resistant to oestrogen therapy, they can be successfully treated with anti-oestrogen therapies,” added Traphagen. “This finding suggests that treatment with oestrogen can re-sensitise patients’ tumours to anti-oestrogen therapies, even if those tumours had previously acquired resistance to anti-oestrogen treatments.”
The researchers will not study the molecular characteristics of breast cells that respond to oestrogen therapy to help predict and improve selection of patients who may respond, and to inform development of new drug combinations that can help optimise the anti-cancer effects of oestrogen therapy.