Targeting drug-resistant breast cancer with estrogen

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

The team’s unconventional approach has exciting implications for breast cancer patients by suggesting that short-term estrogen treatment before resistance to anti-estrogen therapy occurs, and then switching to a more standard anti-estrogen therapy may better control tumor growth in the long term. Traphagen and Miller recently 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.

“While we generally think of estrogens as a nourishment for breast cancer growth, estrogen treatment may induce tumor regression in some patients with anti-estrogen-resistant breast tumors,” says Miller. Despite the fact that estrogen treatment is effective in some patients, estrogen therapy is rarely used. An ongoing clinical trial at NCCC (POLLY; NCT0218875) will determine whether the cycling strategy between estrogen therapy and anti-estrogen therapies is effective in human patients with advanced breast cancer.

“Tumors that initially respond to estrogen therapy eventually develop resistance to it by reducing the amount of estrogen receptors in the tumor cells. Once these tumors become resistant to estrogen therapy, they can be successfully treated with anti-estrogen therapies,” says Traphagen. “This finding suggests that estrogen treatment may re-sensitize patients’ tumors to anti-estrogen therapies, even if those tumors had previously acquired resistance to anti-estrogen treatments.”

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


Todd W. Miller, PhD, is co-director of the Cancer Biology and Therapeutics Research Program and of the Molecular Tumor Board of the Norris Cotton Cancer Center (NCCC) of Dartmouth and Dartmouth-Hitchcock, Scientific Director of the NCCC’s Comprehensive Breast Program and University Associate Professor of Molecular and Systems Biology at Geisel School of Medicine in Dartmouth. Research in the Miller lab focuses on the identification of cancer signaling pathways and the development of targeted therapies for breast and other cancers.

About Norris Cotton Cancer Center

Located on the Dartmouth-Hitchcock Medical Center (DHMC) campus in Lebanon, NH, Norris Cotton Cancer Center combines advanced cancer research at Dartmouth College’s Geisel School of Medicine in Hanover, NH with the highest levels of high quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as regional, multidisciplinary locations and partner hospitals in NH and VT. NCCC is one of only 51 centers nationwide to be awarded the National Cancer Institute’s prestigious “Comprehensive Cancer Center” title, the result of an excellent partnership between DHMC, New Hampshire’s only academic medical center, and Dartmouth College . As the fifth decade enters, NCCC remains committed to excellence, outreach and education, striving to prevent and cure cancer, improve survival and promote cancer health equality through cutting-edge interdisciplinary research. Each year, the NCCC schedules 61,000 appointments with nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.

About Dartmouth-Hitchcock Health

Dartmouth-Hitchcock Health (D-HH), New Hampshire’s only academic health system and the state’s largest private employer, serves a population of 1.9 million people in northern New England. DH provides access to more than 2,000 health care providers in nearly every field of medicine and delivers care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was again named as the # 1 hospital in New Hampshire by US News & World Report in 2020, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the country; the Children’s Hospital at Dartmouth-Hitchcock, the state’s only children’s hospital; affiliated hospitals in Lebanon, Keene and New London, NH and Windsor, VT, and Visiting Nurse and Hospice for Vermont and New Hampshire; and 24 Dartmouth-Hitchcock clinics providing outpatient services in New Hampshire and Vermont. The DH system annually trains nearly 400 residents and fellows and conducts world-class research in partnership with the Geisel School of Medicine in Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.

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