Mayo Clinic and Bon Secours Lead Evangeline Trial Testing (Z)-Endoxifen for Premenopausal Breast Cancer
Key Insights
The Evangeline Phase 2 clinical trial is evaluating (Z)-endoxifen as a chemotherapy-free treatment for premenopausal women with early-stage estrogen receptor-positive breast cancer (search).
Mayo Clinic researchers report success rates of 80% to 90% with endoxifen, which targets estrogen receptors without causing the severe menopausal side effects associated with current treatments.
The trial addresses a growing medical need as breast cancer (search) rates are rising among women under 50, with physicians reporting increased diagnoses in patients in their twenties and thirties.
The Evangeline national clinical trial is testing a promising new approach to treat premenopausal women with breast cancer (search) without chemotherapy, offering hope for improved outcomes while preserving quality of life. Led by Atossa Therapeutics in collaboration with Mayo Clinic and participating centers including Bon Secours Cancer Institute (search), the Phase 2 study is evaluating (Z)-endoxifen in women with newly diagnosed early-stage estrogen receptor (search)-positive (ER+/HER2-) breast cancer.
Rising Incidence in Young Women
Breast cancer (search) rates are increasing among women under 50, creating an urgent need for better treatment options. Dr. William Irvin of Bon Secours Cancer Institute (search) reports a dramatic shift in patient demographics: "Where it used to be I would see somebody in their thirties three or four times a year, it's now three or four times a month."
According to Matthew Goetz, professor of oncology and pharmacology at Mayo Clinic, estrogen receptor-positive breast cancer (search) represents 70% to 80% of all breast cancer (search) cases and has particularly increased in women in their late 20s and early 30s. This hormone-driven cancer type accounts for more than 70% of cases, as noted by Dr. Irvin.
Current Treatment Limitations
For estrogen receptor-positive breast cancer (search), the primary treatment strategy involves blocking estrogen rather than using chemotherapy. "In estrogen-positive breast cancer (search), a lot of the times, you know 70% plus, we're trying not to give chemotherapy or chemotherapy is not indicated. So the mainstay of medical therapy is blocking estrogen," Dr. Irvin explained.
However, current treatments present significant challenges for younger patients. Aromatase inhibitors (search), while effective, cause severe side effects in premenopausal women by inducing early menopause. "For some women, those symptoms can be fairly significant, including hot flashes, they can include joint pain, they can include bone loss," Goetz said.
Tamoxifen, traditionally used for premenopausal women because it doesn't shut down ovarian function, has its own limitations. "Tamoxifen doesn't work very well in the pre-surgery setting while the tumor is still in the body," Dr. Irvin noted. Additionally, "Tamoxifen has been shown not to work as well in young women," according to Goetz.
The Endoxifen Advantage
The Evangeline trial is investigating (Z)-endoxifen, a metabolite produced when tamoxifen breaks down in the liver. Rather than relying on the body's variable conversion of tamoxifen, patients in the trial receive endoxifen directly.
"Endoxifen is a metabolite of an older drug that's been used for many years called Tamoxifen," Goetz explained. "This metabolite has been shown to be substantially more potent and, in fact, very effective for the treatment of breast cancer (search) that's postmenopausal."
Dr. Goetz's laboratory at Mayo Clinic developed this new medication specifically to target estrogen receptors without causing substantial side effects. "The hypothesis and preliminary data show that it will be superior to Tamoxifen in treating breast cancer (search)," Dr. Irvin said.
Trial Design and Early Results
The Evangeline trial follows a structured protocol where patients receive endoxifen for four weeks before surgery. After this treatment period, clinicians conduct a biopsy to assess how effectively the medication stops cancer cell growth.
Early results are encouraging. Dr. Goetz reports success rates as high as 80% to 90% with endoxifen treatment. The Bon Secours Cancer Institute (search) has enrolled two patients in the trial so far.
Clinical Impact and Timeline
(Z)-endoxifen represents a potential breakthrough for premenopausal breast cancer (search) patients by offering a non-chemotherapy treatment option that doesn't impact ovarian function. This approach could significantly improve quality of life while maintaining therapeutic efficacy.
"So as drugs and knowledge and technology have gotten better, we've always been able to improve upon that, improve quality of life, improve cure rates. So this is really one of those next steps," Dr. Irvin said.
The national trial is expected to complete enrollment and data collection by the end of 2026, potentially paving the way for a new standard of care for young women with hormone receptor-positive breast cancer (search).