Adjuvant dose-dense chemotherapy is not associated with improved recurrence-free survival in early-stage, node-negative, HER2-negative breast cancer

Introduction: Adjuvant dose-dense (DD) chemotherapy improves outcomes in early-stage, node-positive breast cancer and is often extrapolated to node-negative disease despite limited evidence and increased toxicity. Whether DD chemotherapy confers benefit in this low-risk population remains unclear. Methods: Females aged ≥ 18 years with T1-T2, node-negative, HER2-negative breast cancer who received adjuvant DD or non-DD chemotherapy were retrospectively identified. Recurrence-free survival (RFS) was defined as the time from definitive surgery to first documented recurrence; patients without recurrence were right-censored at their last disease-free clinical or imaging assessment. Median follow-up duration was estimated using the reverse Kaplan-Meier method. RFS was compared using log-rank tests, and adjusted hazard ratios (HRs) were estimated using multivariable Cox proportional hazards regression. Results: A total of 139 patients were included, 50 (36%) of whom received DD chemotherapy. Patients treated with DD chemotherapy were younger (50 vs. 56 years, P < 0.001) and had higher rates of T2 tumors (48% vs. 27%, P = 0.012), with no significant differences in hormone receptor status, tumor focality, or lymphovascular invasion. Over a median follow-up duration of 9.9 years (95% CI: 9.0-11.2), 17 patients (12%) developed recurrence (7/50 [14%] in the DD group and 10/89 [11%] in the non-DD group). There was no difference in RFS between DD and non-DD groups ( P log-rank = 0.509). After adjustment for age, hormone receptor status, T stage, tumor focality, and lymphovascular invasion, DD chemotherapy was not associated with reduced recurrence risk (HR: 0.97 [95% CI: 0.26-3.26], P = 0.961). These findings were consistent across T stages, with no difference in RFS in either T1 ( P log-rank = 0.947) or T2 ( P log-rank = 0.755) subgroups, and no significant interaction between treatment regimen and T stage ( P interaction = 0.512). Conclusions: DD chemotherapy was not associated with a reduction in recurrence risk among patients with early-stage, node-negative, HER2-negative breast cancer, even after adjustment for clinical and pathological characteristics. Although limited by a low number of recurrence events, these findings suggest that routine use of DD chemotherapy in this low-risk population may not be justified. Larger prospective studies are needed to identify whether any subset of patients derives meaningful benefit.