Chemotherapy use among women < 50 years with hormone receptor–positive breast cancer with low (≤15) Oncotype DX 21-gene recurrence score: A National Cancer Database (NCDB) analysis.

544 Background: RxPONDER demonstrated a benefit to chemotherapy (CT) in premenopausal women with hormone receptor-positive (HR+) breast cancer (BC) with 1-3 pathological positive lymph nodes (pN1) regardless of Oncotype DX RS. Whether the benefit is due to the cytotoxic effects of CT itself or potentially from the CT-induced ovarian suppression remains to be determined. In the absence of large prospective data evaluating the predictive ability of RS in this population, including pN1mi, we sought to examine adjuvant CT use patterns among premenopausal women and low RS. Methods: This retrospective analysis queries the NCDB from 2018-2022 for patients (pts) with BC <50 years old (surrogate for premenopausal status) and clinically node negative disease at the time of diagnosis. Pts with stage I-III HR+ HER2-negative BC who underwent upfront curative breast surgery and had pathologically confirmed lymph node status (pN) were included. Oncotype DX RS was categorized as low if RS ≤15. Multivariable binary logistic regression was used to examine associations between clinical-pathological factors and the receipt of adjuvant CT. Results: 6040 pts with Oncotype DX RS ≤15 met inclusion criteria. Most pts, 5090 (84.3%), had invasive ductal carcinoma, and high (>51%) ER and PR expression (>93% of patients). Among all low RS, 5081 (84.4%) had pN0 and 939 (15.5%) had pN1 or higher disease, 704 pts (76.6%) having 1 LN involved, of which 317 pts were pN1mi; 148 (16.1%) had 2 LN and 67 (7.3%) had 3+ LN. Accounting for all pts, 265 (4.4%) received CT: 64 (24.2%) were pN0, while 201 (75.8%) were pN1+. Among pts with pN1 BC, older age was associated with lower odds of receiving adjuvant CT (aOR 0.96, 95%CI 0.93-1.00, p=0.03). Other factors including higher pathologic tumor stage (pT3/T4 vs pT1/T2; aOR 4.46, 95% CI 2.34–8.51), higher pN involvement, specifically 2 LN (aOR 2.45, 95% CI 1.60–3.75) and ≥3 LN (aOR 4.65, 95% CI 2.54–8.51) compared to 1 positive regional LN, and poorly (vs well) differentiated tumor (aOR 2.36, 95% CI 1.14–4.88) had higher odds of receiving CT. Similarly, pts with pN0 and low RS that had pT3/T4 tumors (aOR 3.99, 95% 1.16-13.72) and higher grade (moderately and poorly differentiated tumors) had higher odds of receiving CT (aOR 1.84 95% CI 1.03-3.27 and 6.11 95% CI 2.58-14.44, respectively). Conclusions: Among women <50 years with low RS (≤15), CT receipt was strongly associated with clinicopathologic risk factors, including higher tumor stage, poorly differentiated grade and higher regional nodal involvement. These findings indicate that despite a low RS, young age and node positivity are associated with adjuvant CT recommendation. These results highlight the importance of ongoing trials such as OFSET, which aims to better answer the appropriateness of CT among premenopausal women.