Neoadjuvant endocrine therapy in BC care: When will the US catch up to European colleagues?

By Lisa Marie Basile | Fact-checked by MDLinx staff

Published March 8, 2025

Key Takeaways

Conference Buzz

“Our European colleagues would argue they’re years ahead of us with neoadjuvant endocrine therapy.” — Jo Chien, MD, breast oncologist and Medical Director of Breast Medical Oncology at UCSF
“NET provides a rich research platform to assess MOA, PK, and PD, as well as mechanisms of resistance. It is also a potential platform to test novel agents and combinations in HR+/HER2— disease, inform adjuvant trials, and patient selections." — Jo Chien, MD

This article is part of our Miami Breast Cancer Conference 2025 coverage. Explore more.

Neoadjuvant endocrine therapy (NET) is typically administered prior to surgery, with a two-fold goal: to conserve the breast and to reduce tumor size.

But it hasn’t exactly caught on in the US as it has in Europe, according to Jo Chien, MD, breast oncologist and Medical Director of Breast Medical Oncology at UCSF. “Our European colleagues would argue they’re years ahead of us with neoadjuvant endocrine therapy,” she explained to attendees of Miami Breast Cancer Conference 2025, day 2.

The fact is, NET remains under-utilized in the US. For post-menopausal women, only limited clinical guidelines exist to help guide treatment,^[] and Dr. Chien says that for premenopausal women, "NET should not be offered routinely outside a clinical trial."

The role of NET

Dr. Chien describes NET as “a nebulous concept,” noting it offers disease control for patients who are not good candidates for surgery and/or chemotherapy. Patient response to NET also plays an evidence-based prognostic role, she says.

“NET provides a rich research platform to assess MOA, PK, and PD, as well as mechanisms of resistance. It is also a potential platform to test novel agents and combinations in HR+ HER2-negative disease, inform adjuvant trials, and patient selections,” Dr. Chien says. She explains how the data supports endocrine therapy over surgery—for post-menopausal women, it actually improves breast conservation rates. “Many patients do not benefit much from neoadjuvant chemotherapy (NCT), especially in post-menopause,” she says. “For post-menopausal women, neoadjuvant ET with an aromatase inhibitor may increase loco-regional options; if no intent for surgery, it may be used for disease control,” she says.

Ongoing trials and challenges

Conducting NET trials can be challenging. “There is a wide range of primary endpoints selected for these trials, so there's really no accepted gold standard biomarker for trials,” Dr. Chien says. The biomarker serves as a surrogate marker for long-term outcome; currently, Ki-67 is the most validated biomarker, according to Dr. Chien.

She also noted a few resources physicians can refer to for more information, including:

The PeriOperative Endocrine-Therapy for Individualised Care (POETIC) trial, which looked at the long-term outcome and prognostic value of Ki-67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer.
Postmenopausal Estrogen/Progestin Interventions (PEPI) index. PEPI 0 is another biomarker validated to show low risk of recurrence after NET. PEPI was developed based on the PO24 trial to assess risk of relapse.
NET trials with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which are used in breast cancer treatment in combination with NET.

Limited studies for premenopausal women

In the end, NET can be used to increase surgical options for postmenopausal patients and in those who are poor candidates for both surgery or chemotherapy, Dr. Chien explained. That said, “There are few NET studies including premenopausal women." However, “small trials have demonstrated similar Ki-67 suppression between pre- and postmenopausal patients,” she says.