Neoadjuvant Endocrine Therapy Could Sway Breast Cancer Radiation Paradigms

Ninety days of endocrine therapy before surgery could change patient/surgeon preference on concurrent radiation use in those with breast cancer.

Endocrine therapy for 90 days prior to surgery and radiation therapy saw increased preference among patients and surgeons while allowing for an additional method to inform adjuvant therapy decisions, according to findings from the phase 2 POWER trial (NCT04272801) presented at a press briefing for the 26th Annual Meeting of American Society of Breast Surgeons.

The trial aimed to assess whether giving 90 days of endocrine therapy would change the patient and surgeon preferences for radiation therapy. Additionally, investigators hoped to gain preliminary data on the impact of pre-endocrine therapy decision conflict or regret.

Of the 75 women enrolled, 95% completed endocrine therapy, with 47% experiencing adverse effects like fatigue, hot flashes, or arthralgias. The investigators noted there was a low level of decisional conflict with no change between the time points, which included those who had changed preference. Overall, 41.3% of patients received radiation therapy.

After pre-endocrine therapy, 28% (P <.001) of patients and 24% (P = .015) of surgeons changed their preferences. Additionally, the agreement between surgeons’ and patients’ preferences for radiation therapy increased significantly from 53.3% (κ = .03) to 81.3% (κ = .6; P <.001).

“The POWER trial allows patients to assess tolerance to endocrine therapy before making adjuvant therapy decisions,” said Shayna L. Showalter, MD, a professor in the Department of Surgery and the Division of Surgery - Breast and Melanoma Surgery at the University of Virginia Health. “Pre-[endocrine therapy] is an innovative method to inform adjuvant therapy decisions.”

Between 2020 and 2024, 75 women were enrolled with a median age of 73. Of note, 4 did not complete the radiation therapy preference survey. Eligible patients had estrogen receptor (ER)–positive or HER2-negative disease with tumors of 2 cm or less.

On day 1, the radiation therapy preferences of patients and surgeons were taken; patients were then given preoperative endocrine therapy. The surveys collected information on patient-reported outcomes (PROs), patient beliefs, and the decisional conflict assessment. On days 30 and 90, PRO surveys were taken again. Patients then moved on to receive breast-conserving surgery with or without radiation therapy followed by adjuvant endocrine therapy. The first follow-up visit was conducted at 2 weeks post-surgery or radiation therapy, with PRO surveys administered. At the 6, 12, and 24-month follow-up visits, PRO surveys and decisional regret assessments were taken.

Showalter noted the trial came from the need for personalized treatment plans and the fact that most older patients received radiotherapy for ER-positive early-stage invasive breast cancer.

Regarding patient preference for radiation therapy prior to endocrine therapy, 10.7% noted it was very unlikely, 49.3% noted it was unlikely, 30.7% noted it was likely, and 9.3% noted it was very likely. After endocrine therapy, 26.7% noted it was very unlikely, 32.0% noted it was unlikely, 20.0% noted it was likely, and 21.3% noted it was very likely.

The rates of surgeon recommendations for radiation therapy before endocrine therapy were 10.7% for very weak recommendations, 64.0% for weak, 21.3% for strong, and 4.0% for very strong. After endocrine therapy, recommendation rates were 30.1% for very weak, 46.7% for weak, 12.0% for strong, and 10.7% for very strong.

Looking towards the future, Showalter hopes the POWER II trial (NCT06507618) will clarify the impact on the over- or under-treatment of this patient population with endocrine therapy prior to surgery. Additionally, she noted the potential to create a paradigm shift for those who are older with early-stage ER-positive breast cancer.

Reference

Showalter SL, Turkheimer L, Meneveau M, et al. 90 days of pre-operative endocrine therapy informs patients and physician preference for radiation therapy: primary results from the POWER trial. Presented at the American Society of Breast Surgeons Press Briefing; April 24, 2025.