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Know someone who鈥檚 been diagnosed with breast cancer? There鈥檚 a good chance that person has received hormone therapy. Estrogen receptor-positive (ER+) breast cancers account for about 75 percent of cases. Hormone therapy is one of the most common and effective treatments. However, it鈥檚 far from a cure. Some ER+ tumors develop resistance. Many patients enter remission only to see the disease return in a form that can鈥檛 be treated with hormone therapy. Now, biologists at Cold Spring Harbor (CSHL) have made a discovery that could someday help prevent breast cancer recurrence and lead to better patient outcomes.

Research from CSHL Associate Professor Camila dos Santos鈥� lab shows that inhibiting the BPTF protein in mice can slow ER+ cancer metastasis and restore tumors鈥� susceptibility to hormone therapy. The finding could have 鈥渉uge implications for making cancer more treatable,鈥� says Michael Ciccone, a former researcher in the lab. 鈥淲e鈥檙e not curing cancer, but we’re forcing it into an avenue that we鈥檙e good at, which is targeting it with hormone therapies.鈥�

Previous research had found that knocking out BPTF slows breast cancer growth but doesn鈥檛 stop tumors from forming. As such, pharmaceutical companies didn鈥檛 see much promise in the protein. However, Ciccone and his lab-mates, graduate student Dhivyaa Anandan and postdoc Deeptiman Chatterjee, saw untapped potential. To learn more, they bred a classic breast cancer mouse model with a BPTF knockout mouse. To their surprise, they found the tumors in the crossbred mice remained ER+ throughout their development.

鈥淭丑别re isn鈥檛 any mouse model that maintains a hormone-positive cancer throughout the cycle of the tumor,鈥� Ciccone said. When treated with , one of the most common hormone therapies for ER+ breast cancer, the tumors were 鈥渞esponding and not growing,鈥� he said. 鈥淭hat鈥檚 when we realized that we were onto something.鈥�

The team tested a combination of BPTF loss and tamoxifen in organoid systems, human breast cancer cell lines, and mouse models resistant to hormone therapy. In all cases, the combination restored sensitivity to treatment. 鈥淥ur work highlights biological mechanisms that are not only very fascinating, but translatable,鈥� Chatterjee said.

Anandan emphasized that it was the group鈥檚 fundamental approach to research that made their discoveries possible. 鈥淐ancer is often studied in a binary way,鈥� she says. 鈥淚s it there or not? Did the tumors grow or shrink? This study showed there is far more nuance. If we don鈥檛 look at the types of tumors that are growing, how they鈥檙e growing, and where they鈥檙e spreading鈥攁ll the very nuanced analyses we did鈥攚e miss so much.”

Written by: Margaret Osborne, Science Writer | [email protected] | 516-367-8455

Funding

Pershing Square Sohn Cancer Research Alliance, Simons Foundation, CSHL-Northwell Affiliation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences

Citation

Ciccone, M.F., et al., 鈥淟oss of BPTF restores estrogen response and suppresses metastasis of mammary tumors鈥�, Nature Communications, October 15, 2025. DOI:

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鈥淭丑别 Animal Shared Resource houses and cares for the animals essential for scientific research. Our staff perform all aspects of animal husbandry, ensure humane care, and assist researchers with highly technical procedures and protocol design and development.鈥� 鈥� Animal Facility Director and Attending Veterinarian Rachel Rubino, DVM

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