1 min readTargeting Drug-Resistant Breast Cancer with Oestrogen

Lebanon, NH — Researchers at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) hope to make oestrogen therapy a more accessible treatment option for breast cancer patients who could benefit from it. Anti-oestrogen treatments, which block growth signals from oestrogen receptors (ER) in tumours, are effective treatments for ER+ breast cancer. But it is common for breast tumours to become resistant to anti-oestrogen treatments over time. The research team, led by molecular biologist Dr. Todd Miller and Nicole Traphagen, a PhD candidate in the Miller Laboratory, found that in mice, cycling between oestrogen treatment and anti-oestrogen treatment at a specific point in time can dramatically increase the duration of tumour regression. 

The team’s unconventional approach has exciting implications for breast cancer patients by suggesting that treating short-term with oestrogen before anti-oestrogen therapy resistance occurs, and then switching back to a more standard anti-oestrogen therapy can better control tumour growth long-term. Traphagen and Miller have newly published their findings, entitled “High estrogen receptor alpha activation confers resistance to estrogen deprivation and is required for therapeutic response to estrogen in breast cancer,” in Oncogene.

“Although we typically think of oestrogens as feeding breast cancer growth, treatment with estrogens can actually induce tumour regression in some patients with anti-oestrogen resistant breast tumours,” says Miller. Despite the fact that oestrogen treatment is effective in some patients, oestrogen therapy is rarely used. An ongoing clinical trial at NCCC (POLLY; NCT0218875) will determine whether the strategy of cycling between oestrogen therapy and anti-oestrogen therapies is effective in human patients with advanced breast cancer.

“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-estrogen therapies,” says Traphagen. “This finding suggests that treatment with oestrogen can re-sensitize patients’ tumours to anti-oestrogen therapies, even if those tumours had previously acquired resistance to anti-oestrogen treatments.”

Miller and Traphagen will also study the molecular characteristics of breast cells that respond to oestrogen therapy. The goal is to use this information to predict and improve selection of patients who may respond to oestrogen therapy and inform development of new drug combinations to optimize the anti-cancer effects of oestrogen therapy.

Article adapted from a Dartmouth-Hitchcock Medical Center news release.

Publication: High estrogen receptor alpha activation confers resistance to estrogen deprivation and is required for therapeutic response to oestrogen in breast cancer. Traphagen, NA et al. Oncogene (April 19, 2021): Click here to view.

Breast Cancer, oestrogen, oestrogen therapy

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