Abstract Introduction: Older women with early-stage luminal A breast cancer tend to have an excellent prognosis with a 5-year relative survival exceeding 99%. Ongoing research on curtailing overdiagnosis and overtreatment have challenged long established standards of care by reducing the use of whole breast radiotherapy and selectively omitting sentinel lymph node biopsy. In light of emerging data suggesting that endocrine therapy can be safely omitted in older women with ultra-low risk luminal A breast cancer, the marginal utility of Oncotype Dx genomic testing was explored. Materials and Methods: We queried the Good Samaritan University Hospital Cancer Registry to identify consecutive breast cancer patients treated from 2014 through 2022. Based on extensive research on radiation omission and selecting patients for partial breast irradiation, we defined an ultra-low risk breast cancer population as age ≥60 years, estrogen receptor ≥1% positive, progesterone receptor 20% positive, HER2-negative, pathologic stage T1b-T2N0, well to moderately differentiated, no lymphovascular invasion, and Ki-67 ≤13.25%. The primary endpoint was the proportion of patients with low (0-18) or intermediate (19-25) risk Oncotype scores, for which chemotherapy is not indicated. Secondary endpoints included local recurrence and overall survival. Results: Out of 1711 patients, 91 met all ultra-low risk eligibility criteria. Median age was 70 years (IQR 65-74; range 60-85) and median breast tumor size was 10 mm (IQR 7-15). Most patients were diagnosed with invasive ductal carcinoma (71.4%) or lobular carcinoma (16.5%). All patients underwent surgical intervention, with 79.1% receiving a lumpectomy and 20.9% receiving a mastectomy. Sixty-nine (75.8%) patients received post-operative radiotherapy and no patients received chemotherapy. The median follow-up was 5.14 years. Only 1 of 91 patients (1.1%) had a high risk Oncotype Dx score of 26, while 12 (13.2%) had an Oncotype Dx score of 19 to 25 and 78 (85.7%) scored 0 to 18. Five-year local control and overall survival was 100% and 93%, respectively. Nine deaths occurred, none related to breast cancer, and no patients developed distant metastases. Conclusion: We describe a pragmatic method of using clinical and pathological features routinely available in a community hospital breast program to define an ultra-low risk cohort. Older luminal A patients with favorable pathology have a very low probability of a high Oncotype Dx genomic score and have an excellent prognosis with standard adjuvant therapy. Future research for ultra-low risk breast cancer patients should focus on treatment de-escalation beyond radiotherapy. Citation Format: M. Schmalzle, R. Radigan, S. Singh, W. Liu, K. Deng, M. Fabrikant, R. Shah, S. L. Fu, J. Kao. Omitting Oncotype Dx Genomic Testing in Ultra Low Risk Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-04.
Schmalzle et al. (Tue,) studied this question.