American College of Surgeons Oncology Group (ACOSOG) Z0010 trial (1999-2003) aimed to evaluate potential predictive factors for recurrences in patients with H&E negative sentinel lymph nodes (SLNs). Eligibility criteria for this multicentre prospective trial included patients with T1-T2, N0, M0 invasive breast cancer who were planned for breast conserving surgery (BCS) with whole breast irradiation. SLNs were assessed for metastasis with standard H&E staining. For patients who had H&E negative SLNs, further immunohistochemistry (IHC) was performed with anti-cytokeratin antibodies. The clinicians were blinded to the IHC results. The incidence of occult metastasis in this group was 10.3%. 5539 patients were recruited from 126 participating sites, and 3904 patients (76.3%) had H&E negative SLNs. Median follow up was 8.4 years. 92.2% of patients completed whole breast irradiation, 43.5% completed adjuvant chemotherapy, and 67.7% completed adjuvant hormonal therapy. There were 127 local, 20 regional, and 134 distant recurrences, and 317 deaths reported. 5 year incidence rates for local recurrence, regional recurrence, and distant recurrence were 2.4%, 0.5%, and 2.8% respectively. There was no difference in recurrence rates between H&E and IHC negative SLNs compared to H&E negative, and IHC positive SLNs. On multivariate analysis, older age (p=0.018, HR 0.98) and positive hormonal status (p<0.0001, HR 0.34) predicted for reduced local failure. Lymphovascular invasion (p=0.008, HR=2), grade 2 disease (p=0.005, HR 2.44), and grade 3 disease (p=0.0003, HR 3.65) predicted for distant recurrences. Older age (p<0.0001, HR 1.07), increasing tumour size (p=0.0013, HR 1.18), and grade III disease (p<0.0001, HR 2.65) predicted for reduced overall survival. When local recurrence was included in the model as a time-dependent variable, older age, T2 disease, higher tumour grade, and local recurrence were associated with reduced overall survival.
Annals of Surgery 2012, DOI: 10.1097/SLA.0b013e3182654494
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