Adjuvant chemotherapy in T1a/bN0 breast cancer with a high 21-Gene Recurrence Score (>25): A 10-year follow-up in a real-world cohort

Background In ER+/HER2- early breast cancer (BC), a 21-Gene Recurrence Score (RS) > 25 indicates a high-risk of distant-recurrence and a predictes benefit from adjuvant chemotherapy (aCT), independent of tumor size. However, T1a/b (≤ 1cm) node negative (N0) tumors, that are usually regarded clinically as of very low risk of recurrence, are under-represented in trials validating the prediction role of RS testing. We therefore aimed to investigate the benefit of aCT in patients with T1a/bN0 BC and RS > 25, where clinical and genomic risk indicators are discordant. Methods The study cohort included all patients with T1a/bN0 ER+/HER2- BC with RS > 25, tested within Clalit Health Services (CHS), Israel’s largest healthcare provider, between February 2006 and December 2019. Demographic, clinicopathological and treatment data were extracted from the CHS centralized registry. Patients who received aCT were matched 1:1 by propensity-scoring to patients receiving no aCT. Invasive disease-free survival (iDFS) events and freedom from iDFS were primary endpoints. Distant-recurrences and freedom from distant-recurrence were the secondary endpoints. Kaplan-Meier analysis with log-rank test was used for comparing the study outcomes. Results Among 9858 CHS patients tested for RS during the study period 156 met the inclusion criteria. aCT was administered to 74 (47.4%) patients. Median follow-up was 121.0 months (95% CI, 108.4 -133.6). Within the 148 matched-cases, eighteen iDFS events occurred, nine (12.1%) in each treatment group (χ ²  = 0.72, p = 0.39). Four (5.4%) of the aCT treated and three (4.0%) of the untreated patients were diagnosed with a distant recurrence (\(\:\chi\:2=0.22,\:\) p =0.64). Conclusions In our cohort, with a mean follow-up of 10-years, patients with T1a/bN0 BC and RS > 25, did not show improved iDFS with aCT compared to those who did not receive aCT. The 21 Gene Recurrence Score (RS) > 25 was not predictive of iDFS, possibly due to the low number of events observed.