A new HRT med could change the breast cancer risk equation
Industry Buzz
This is a pivotal moment addressing a significant unmet need in women's health. d3-T could significantly enhance options for hormone therapy in menopausal and perimenopausal women.
—Barbara S. Levy, MD, via a press release
These results suggest that AVA-291 may be a useful alternative to T in clinical situations where the aromatization of T limits its therapeutic potential, such as hormone replacement therapy in postmenopausal women.
—The study authors
A novel hormone replacement therapy (HRT) candidate designed to overcome longstanding safety concerns around testosterone use in women is showing early promise in reducing breast cancer risk, according to new findings presented at the American Association for Cancer Research 2026 annual meeting.[]
The investigational drug, AVA-291 (d3-testosterone), is a modified form of testosterone engineered to resist "aromatization"—the biological process by which testosterone is converted into estrogen in tissues.[]
This conversion has been associated with increased proliferation of estrogen receptor-positive (ER+) breast cancer cells and has historically limited the development of testosterone-based therapies for women.
What the findings show
In preclinical data, researchers compared standard testosterone with AVA-291 in ER+ breast cancer cells. Consistent with prior evidence, testosterone stimulated tumor cell proliferation in a concentration-dependent manner.[]
In contrast, AVA-291 showed no significant proliferative effect over comparable ranges, with activity observed only at much higher concentrations.[]
The difference appears to stem from AVA-291's resistance to aromatization. By preventing conversion into estradiol, the drug may avoid the downstream signaling that drives tumor growth in hormone-sensitive breast cancers.[]
"These results suggest that AVA-291 may be a useful alternative to T in clinical situations where the aromatization of T limits its therapeutic potential, such as hormone replacement therapy in postmenopausal women," the authors note.
Unlike conventional testosterone, d3-T’s resistance to aromatization may significantly reduce the risk of estradiol-driven side effects, including breast cancer and gynecomastia, making it a potentially transformative therapy for patients.[]
What it means for the future of women’s health
The development comes amid growing interest in testosterone therapy for women—particularly for symptoms such as low libido and fatigue—but also ongoing concern about safety.
"This is a pivotal moment addressing a significant unmet need in women's health,” Barbara S. Levy, MD, chief medical officer at Visana Health Inc., said in a press release. “d3-T could significantly enhance options for hormone therapy in menopausal and perimenopausal women."[]
AVA-291’s developer, Aviva Bio, is positioning the drug as an alternative that retains the benefits of testosterone while mitigating cancer risk. In January, the FDA shared formal feedback with the company regarding the requirements for the development of a testosterone-based therapy for women.[]
In its feedback, the FDA highlighted the potential link between testosterone use and breast cancer risk as a key barrier to broader adoption.[]
Despite encouraging early data, the findings are preclinical and have yet to be confirmed in large clinical trials. A phase 1 clinical trial is expected to begin this year.[]
If validated in clinical settings, AVA-291 could mark a significant advance in hormone therapy, offering a safer option for women requiring androgen-based treatment without increasing breast cancer risk.