The Phase 2 clinical trial PremiÈRe (SOLTI-2104) is the first to evaluate the oral drug elacestrant -either alone or combined with ovarian function suppression- in premenopausal women with early HR+/HER2- breast cancer
After 4 weeks of treatment, during the pre-surgery period, significant reductions were observed in cell proliferation indices in patients’ tumors and a shift towards less aggressive molecular profiles. The results suggest that elacestrant could become a new oral endocrine therapy option for young women, with potential to avoid ovarian suppression in some patients, thereby reducing toxicity and improving treatment adherence. PremiÈRe continues the research line initiated by the SOLTI ELIPSE study, which had already demonstrated the antiproliferative activity of elacestrant in early luminal breast cancer, but in postmenopausal women
The trial, promoted by the academic group SOLTI, was presented today at the San Antonio Breast Cancer Symposium (SABCS) 2025, one of the most influential international breast cancer conferences
The academic research group in breast cancer SOLTI presented today at the San Antonio Breast Cancer Symposium (SABCS) 2025 the results of the Phase 2 PremiÈRe (SOLTI-2104) trial, which evaluates the use of the oral drug elacestrant in premenopausal women with early HR+/HER2- breast cancer, either alone or in combination with other drugs that induce ovarian suppression.
The young patient population is historically an underexplored area, and these results provide the first evidence that elacestrant, a highly innovative drug from the “selective estrogen receptor degraders” family, is capable of stopping the proliferation of cancer cells and also shows a safety profile consistent with previous data.
Dr. Meritxell Bellet, co-principal investigator of the study, SOLTI Board member, medical oncologist at Vall d’Hebron University Hospital, and researcher at the Vall d’Hebron Institute of Oncology (VHIO) Breast Cancer Group, is the presenter of the study at SABCS 2025.
A specific challenge in young women with early HR+/HER2- breast cancer
Premenopausal women represent nearly 30% of patients with early HR+/HER2- breast cancer. In this group, the standard strategy is based on ovarian function suppression (OFS) combined with tamoxifen or aromatase inhibitors, which has been shown to improve disease-free survival but at the cost of significant toxicity, intense climacteric symptoms, sexual dysfunction, and a major impact on adherence and long-term quality of life.
In this context, the oral drug elacestrant had already shown superiority over standard hormone therapy in patients with metastatic HR+/HER2- breast cancer, and antiproliferative activity in early disease in postmenopausal women in the ELIPSE window trial, also promoted by SOLTI.
“We know that ovarian suppression combined with tamoxifen, and particularly with aromatase inhibitors, is highly effective in reducing the risk of relapse, and even overall survival in high-risk patients, but we also know it’s not a neutral treatment: it involves inducing chemical menopause in young women, with clear impacts on symptoms, hot flashes, joint pain, bone demineralization, sexual difficulties, and long-term adherence,” explains Dr. Bellet.
“With PremiÈRe, we wanted to answer a very specific question: can we use a new generation oral endocrine drug like elacestrant in premenopausal women with early breast cancer and achieve relevant biological activity without needing to suppress ovarian function in all of them?”.
Results: comparable antiproliferative and molecular responses with and without ovarian suppression
The results of the PremiÈRe study show “complete cell cycle arrest” (CCCA) rates of 28.6% in the group treated with elacestrant and 26.9% in the group that received elacestrant plus ovarian suppression, with slightly higher percentages in Luminal A tumors. Both arms also showed a significant reduction in the cell proliferation marker Ki67, with decreases of 62% and 72%, respectively. In parallel, there was a shift towards a less proliferative phenotype, with conversion of PAM50 molecular profiles from high or medium risk to low-risk categories, and from Luminal B tumors to Luminal A or Normal-like. The treatment also showed a safety profile consistent with previously described data for elacestrant in other clinical settings.
“The most important finding in PremiÈRe is that the biological activity of elacestrant has been very similar in both monotherapy and combination with ovarian suppression,” says Dr. Bellet. “We see marked inhibition of tumor proliferation, favorable changes in gene expression, and a shift towards lower-risk profiles, which makes us think this drug could become an attractive oral endocrine therapy option for premenopausal women with early disease.”
Towards rational de-escalation strategies in endocrine therapy
One of the highlights of the study is the potential to de-escalate endocrine treatment in young women, maintaining biological efficacy while reducing the toxicity and complexity associated with prolonged ovarian suppression.
“The main goal of PremiÈRe was to assess the biological effect and safety of elacestrant alone or in combination with ovarian suppression over a short period, prior to surgery,” explains Dr. Tomás Pascual, translational researcher of the trial, SOLTI Board member, and medical oncologist at Hospital Clínic Barcelona. “The results show consistent and very similar antitumor activity between monotherapy and combination, which allows us to suggest, for the first time, that perhaps not all young patients need intensive ovarian suppression to benefit from next-generation endocrine therapies.”
“At a time when we seek effective yet better-tolerated treatments, PremiÈRe provides key information to move towards rational de-escalation strategies in the endocrine therapy of premenopausal women,” adds Dr. Pascual. “The next steps are to validate these findings in larger and comparative studies, expand our understanding of the hormonal changes induced by elacestrant in women without ovarian suppression, and incorporate biomarkers to help identify which patients may benefit from a simpler and more personalized approach.”
Continuity with the ELIPSE study and SOLTI’s academic research
PremiÈRe is part of SOLTI’s window trial program, which takes advantage of the interval between diagnosis and surgery to study in depth the biological impact of new therapeutic strategies in breast tumors, and in this sense, the trial follows up on the ELIPSE study.
“PremiÈRe is a clear example of how independent academic research allows us to ask questions that go beyond classical regulatory development and focus on very specific patient needs,” emphasizes Dr. Bellet. “Our goal is to generate data that helps rethink the standard of care for young women with HR+/HER2- breast cancer, incorporating oral options that can be just as effective, more sustainable, and better integrated into their life plans.”
PremiÈRe is an academic study led by SOLTI in collaboration with multiple research centers and has been supported by Menarini Stemline.
About the PremiÈRe study (SOLTI-2104)
PremiÈRe is a Phase 2, open-label, non-comparative, and randomized trial promoted by SOLTI, which evaluates the biological effect and safety of elacestrant alone or in combination with ovarian function suppression via triptorelin in premenopausal women with early ER+/HER2- breast cancer.
The treatment is administered for approximately 4 weeks prior to surgery or a control biopsy,
