Axillary surgery versus no-axillary staging in T1N0 breast cancer: 20-year follow-up of the INT 09/98 randomized clinical trial

The role of axillary surgery in breast cancer has shifted over time from a therapeutic operation to a staging method for subsequent adjuvant therapies, through the introduction of sentinel lymph node biopsy. The discovery of molecular subtypes has since questioned the necessity of axillary staging in breast cancer. The INT09/98 randomized trial explored the omission of axillary surgery in early-stage breast cancer in patients under 65 years of age. From June 1998 to June 2003, a total of 565 T1N0 breast cancer patients were enrolled. The trial tested the non-inferiority of quadrantectomy without axillary surgery (QU) compared to quadrantectomy with axillary dissection (QUAD). The primary endpoint was overall survival (OS). Secondary endpoints included disease-free survival (DFS) and incidence/timing of axillary lymph node metastasis in the QU arm. Follow-up at 20 years showed no significant differences between the QU versus the QUAD arm. The adjusted hazard ratio for OS was 1.18 (P = 0.326) and DFS was 1.27 (P = 0.280) respectively, both within the predetermined non-inferiority limit. Axillary relapse rates in the QU arm remained low, indicating that only a subset of metastatic nodes cause recurrences if not removed. In the QU arm, patients with favourable biological features but unknown axillary node involvement did not receive adjuvant chemotherapy, without significant differences in outcomes. The axillary relapse rate with distant metastases was similar in both arms and may reflect aggressive biology of the primary tumour. Avoiding axillary surgery and reducing adjuvant treatments in early breast cancer does not increase distant metastases or affect long-term survival. Axillary relapsed patients with distant metastases in both QU and QUAD arms may represent cancers with genomically determined poorer prognosis, independent of surgical intervention and adjuvant therapies. NCT01508546 (http://www.clinicaltrials.gov).