At the 4th National Comprehensive Cancer Network (NCCN) Asia Conference, Professor Carlson, leader of the NCCN Breast Cancer Clinical Practice Guidelines (Guidelines) Expert Panel from Stanford University Medical Center, presented on the key points of the updates in the 2nd edition of the Guidelines in 2011. Sentinel lymph node biopsy Treatment options for patients with positive sentinel lymph nodes The ACOSOG Z0011 trial focused on whether patients with positive sentinel lymph node biopsy (SLNB) breast cancer should undergo further axillary lymph node dissection (ALND) surgery. The trial randomized 856 patients with clinical stage T1 to 2 breast cancer who underwent breast-conserving surgery and had anterior lymph node metastasis into two groups, one with ALND (420 patients) and the other without further axillary surgery (436 patients). The results at a median follow-up of 6.3 years showed no significant difference in local recurrence rates between the two groups (4.1% versus 2.8%, p=0.11), nor were there any significant differences in local area recurrence-free survival, disease-free survival (DFS) and overall survival (OS). According to Prof. Carlson, the trial suggested that for breast cancer patients with negative clinically examined lymph nodes, staged T1-2, with less than three involved anterior lymph nodes and treated with breast-conserving surgery and whole-breast radiotherapy, ALND was associated with more complications and did not significantly improve the rate of locoregional recurrence or OS compared with SLNB only. Therefore, the new version of the guideline adds the recommendation that “axillary lymph node dissection may not be necessary for selected patients with positive anterior lymph nodes”. New drug option for MBC Denosumab for prevention of bone-related events Early data showed that pamidronate disodium reduced the incidence of bone-related events (SRE) compared with placebo in patients with metastatic breast cancer (MBC) with at least one osteolytic bone metastasis. Follow-up studies further suggest that zoledronic acid can further reduce SRE on top of pamidronate disodium. The new drug denosumab is a fully humanized monoclonal antibody that binds to nuclear factor-κB receptor activator (RANK) ligands to inhibit osteoclast activity. in a 2010 study published in the Journal of Clinical Oncology, 2046 patients with advanced osteolytic bone metastases were randomized to receive either zoledronic acid (4 mg ) or denosumab (120 mg ). The incidence of both first or multiple SREs was significantly lower in the denosumab group. Therefore, the new version of the guideline adds the recommendation of “denosumab as an option for the prevention of SRE in patients with bone metastases”. Eribulin monotherapy for MBC Eribulin is a synthetic analogue of halichondrin B, which blocks the formation of microtubulin multimers. The EMBRACE study, reported at the 2010 American Society of Clinical Oncology (ASCO) annual meeting, included 762 patients with advanced breast cancer in lines 2-5 who had received anthracycline and paclitaxel chemotherapy and progressed within 6 months of the last chemotherapy, randomized to eribulin treatment or to treatment by physician’s choice. The results showed significant improvements in objective efficiency (12% versus 5%, P=0.002) and OS (13.12 months versus 10.65 months, P=0.04, HR=0.81) in the eribulin group, and clinical benefit rates (23% versus 17%) and progression-free survival (PFS, 3.7 months versus 2.2 months, P=0.14, HR= 0.87) also showed a trend of improvement. Based on this, eribulin has been approved by the US FDA for the treatment of patients with MBC who have received adjuvant or advanced chemotherapy with anthracyclines and paclitaxel and have received chemotherapy with two or more advanced regimens. Breast cancer biomarkers Hormone receptor, human epidermal growth factor receptor 2 (HER2) re-testing Estrogen receptor (ER), progesterone receptor (PR) and HER2 status may be altered in breast cancer metastases. Therefore, the new version of the Guidelines recommends that re-testing should be considered to determine the ER, PR, and HER2 status of tumors that are unknown and have negative or no overexpression results on the initial test. Clinical significance of CYP 2D6 Tamoxifen can be metabolized by cytochrome P450 2D6 (CYP 2D6) to a more active product. Recent studies have attempted to answer the question of whether changes in the degree of tamoxifen metabolism caused by CYP 2D6 polymorphisms correlate with its efficacy. However, the existing findings are conflicting and it is unclear how to respond to the different CYP 2D6 genotypes, so this year’s Guideline is silent on this issue and does not recommend routine CYP 2D6 testing.