Abstract GS02-08: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer
Authors: Jagsi Reshma , Griffith Kent , Harris Eleanor , Wright Jean , Recht Abram , Taghian Alphonse , Lee Lucille , Moran Meena , Small William , Johnstone Candice , Rahimi Asal , Freedman Gary , Muzaffar Mahvish , Haffty Bruce , Horst Kathleen , Powell Simon , Sharp Jody , Sabel Michael , Schott Anne , El-Tamer Mahmoud 
Published: May 2024

Background:

Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients age 65-70 or older with Stage I breast cancers treated with breast conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy (RT). We designed a prospective single-arm trial, IDEA (Individualized Decisions for Endocrine therapy Alone), to see if younger postmenopausal patients could also be successfully treated without RT, adding a genomic assay to classic selection factors.

Methods:

Postmenopausal patients aged 50-69 with pT1N0 unifocal invasive breast cancer with margins 2 mm or wider after BCS whose tumors were ER+, PR+, and Her2- with Oncotype DX 21-gene recurrence score (RS) 18 or lower were eligible to avoid RT if they consented to take at least 5 years of ET and surveillance on study. The primary endpoint was the rate of breast cancer recurrence at 5 years of follow-up after BCS. A valid 5–year assessment was defined as a clinical assessment within 4 months prior to the 5-year anniversary or later. Follow-up time was calculated from the date of BCS until first recurrence [ipsilateral breast events (IBE) or regional or distant failures] or to last clinical follow-up. The time-to-event endpoint was calculated using the product-limit method of Kaplan and Meier measured from the date of BCS.

Results:

200 eligible patients were enrolled from 13 US institutions between June 2015 and October 2018. Median age was 63 years (IQR 58-66); mean RS was 11.2 (SD 4.8). Tumors were grade 1 in 85 patients, grade 2 in 109, and grade 3 in 6. Mean tumor size was 10 mm (SD 4.6). Lymphovascular invasion was present in 16 tumors and an extensive intraductal component in 11. Median follow-up time was 5.21 years (IQR 5.01-5.97); 8 of 14 patients with less than 56 months of follow-up were lost to follow-up. Overall and breast cancer-specific survival rates at 5 years were both 100%; 2 deaths occurred later than 5 years. The 5-year freedom from recurrence was 99% (95% CI, 96%-100%). One of the two events occurring by 5 years was an isolated axillary recurrence at 21 months treated with axillary dissection and breast and regional nodal irradiation. The other was an IBE at 49 months, treated with repeat BCS. Both these patients had been compliant with ET. Six additional patients recurred later than 5 years after BCS (5 IBEs, 1 IBE plus regional recurrence). Crude rates of IBE for the entire follow-up period for patients aged 50-59 and 60-69 were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall relapse were 5.0% (3/60) and 3.6% (5/140).

Conclusions:

This multicenter trial of ET without RT following BCS achieved a very low risk of relapse for postmenopausal patients with Stage I cancers using a genomic assay in combination with classic clinical and biologic features for treatment selection, including for patients younger than age 60. IDEA demonstrates a 5-year probability of recurrence consistent with or lower than the 4% risk estimated a priori, and the patients accrued were younger when compared to prior prospective trials (e.g., PRIME II, minimum age 65; CALGB 9343, minimum age 70; LUMINA, median age 67). The results of ongoing NRG BR007 trial, which randomly allocates women meeting these eligibility criteria to receive RT or not, and similar randomized and single-arm studies will help determine whether the option of avoiding initial RT can be offered to a broader group of women than current guidelines recommend. Long-term follow-up beyond the 5-year required period of ET will be important to determine if the risk of recurrence increases, particularly after discontinuation of ET.

Citation Format: Reshma Jagsi, Kent Griffith, Eleanor Harris, Jean Wright, Abram Recht, Alphonse Taghian, Lucille Lee, Meena Moran, William Small, Candice Johnstone, Asal Rahimi, Gary Freedman, Mahvish Muzaffar, Bruce Haffty, Kathleen Horst, Simon Powell, Jody Sharp, Michael Sabel, Anne Schott, Mahmoud El-Tamer. Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-08.