Impact of the 21-Gene Oncotype DX Recurrence Score on Adjuvant Chemotherapy Decision-Making in Invasive Ductal Carcinoma: A Real-World Analysis From a Single Japanese Institution.

Background The 21-gene Oncotype DX Recurrence Score (RS) assay (Exact Sciences Corporation, Madison, WI) is a genomic test used to inform adjuvant chemotherapy decisions in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. In Japan, the assay has been reimbursed under national health insurance since September 2023, yet institution-level real-world data restricted to invasive ductal carcinoma (IDC) remain sparse. We therefore characterized the impact of the RS on adjuvant chemotherapy decisions in patients with IDC at our institution. Methods We conducted a single-center, retrospective, observational study of consecutive patients with HR-positive, HER2-negative IDC who underwent Oncotype DX testing at Kanazawa University Hospital between April 2022 and April 2026. Patients who received neoadjuvant systemic therapy were excluded a priori. Pathology was assessed locally rather than through external central review; estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki-67 were evaluated in accordance with the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and the recommendations of the International Ki-67 in Breast Cancer Working Group. Clinical risk was dichotomized using the Adjuvant! Online version 8.0 simplified criteria (developed by Peter M. Ravdin, MD, PhD, at the University of Texas Health Science Center at San Antonio, TX) adopted in the MINDACT trial, and genomic risk was dichotomized at the TAILORx-defined threshold (RS ≤ 25 vs. RS ≥ 26). The primary endpoints were the clinico-genomic discordance rate and the actual rate of adjuvant chemotherapy administration or omission. Ninety-five percent Wilson score confidence intervals (CIs) were calculated for the principal proportions. Results Of 140 consecutive patients tested, 102 were eligible for analysis after exclusion of non-IDC histology (n = 24), missing histological grade (n = 12), an unevaluable RS result (n = 1), and incomplete clinical staging (n = 1). The median age was 55 years (range, 37-78); 59.8% of patients were postmenopausal, and 62.7% were node-negative. The median RS was 16 (range, 0-51); 17 patients (16.7%; 95% CI, 10.6-25.2) had an RS ≥ 26. Sixty-six patients (64.7%) were classified as clinical high risk and 36 (35.3%) as clinical low risk. The overall clinico-genomic discordance rate was 57.8% (59 of 102; 95% CI, 48.1-67.0) and was driven predominantly by the clinical high/RS low-intermediate combination (52.9%, 54 of 102; 95% CI, 43.3-62.4); the opposite, clinical low/RS high pattern accounted for only 4.9% (five of 102; 95% CI, 2.1-11.0). Adjuvant chemotherapy was withheld in 51 of 66 clinical high-risk patients (77.3%; 95% CI, 65.7-85.7) and in 50 of 54 clinical high/RS low-intermediate patients (92.6%; 95% CI, 82.4-97.1). Overall, 17 of 102 patients (16.7%; 95% CI, 10.6-25.2) received adjuvant chemotherapy. Conclusions In this Japanese single-institution IDC cohort, approximately three in five patients showed discordance between clinical and genomic risk, with reclassification overwhelmingly directed toward de-escalation. Oncotype DX testing was associated with the omission of adjuvant chemotherapy in more than three-quarters of clinically high-risk IDC patients, supporting its substantial influence on adjuvant treatment decision-making in routine Japanese clinical practice.