Prognostic impact of radiotherapy dose to the axilla in cN + /ypN0 breast cancer after primary systemic therapy and sentinel lymph node biopsy: toward true de-escalation of axillary management.

BACKGROUND

The optimal extent of axillary radiotherapy in patients with clinically node-positive (cN +) breast cancer who became node-negative on sentinel lymph node biopsy (SLNB) (ypN0 by SLNB) after primary systemic therapy (PST) remains uncertain. While de-escalated axillary surgery has been widely adopted, evidence guiding the necessity and dose of axillary irradiation, particularly to initially involved nodes (ALN_inv), is limited.

METHODS

We retrospectively analyzed 132 patients with cN1-2a breast cancer treated at three institutions between 2009 and 2018. All patients underwent PST, curative breast surgery with SLNB without axillary lymph node dissection, and postoperative radiotherapy. Radiation doses to ALN_inv and axillary levels I-III were reconstructed and expressed as relative mean dose percentages (Dmean%) of the prescribed breast/chest wall dose. Oncologic outcomes were evaluated using Kaplan-Meier and Cox regression analyses.

RESULTS

The median Dmean% values were 91.4% for ALN_inv, 69.5% for level I, 82.9% for level II, and 94.8% for level III. After a median follow-up of 79.0 months, 15 patients (11.4%) developed recurrence, including three axillary recurrences (2.3%), corresponding to a 5-year axillary recurrence-free survival of 98.4%. The 5-year DFS and OS rates were 90.1% and 96.2%, respectively. No clear association was observed between axillary dose and DFS, whereas non-pathologic complete response (HR 3.781, 95% CI 1.055-13.550, p = 0.041) and total mastectomy (HR 4.433, 95% CI 1.535-12.800, p = 0.006) were independently associated with worse DFS.

CONCLUSION

In cN + /ypN0 breast cancer patients treated with PST and SLNB, favorable axillary control and DFS were achieved even with relatively low radiation doses to ALN. No clear association was observed between delivered axillary dose and oncologic outcomes, suggesting the feasibility of tailored de-escalation of axillary radiotherapy. Further prospective studies are necessary to define safe dose thresholds and target volumes.