Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 and NCT00005970.)

No abstract

SummaryTo correlate the variable clinical features of estrogen receptor positive (ER+) breast cancer with somatic alterations, we studied pre-treatment tumour biopsies accrued from patients in a study of neoadjuvant aromatase inhibitor (AI) therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to hematopoietic disorders. Mutant MAP3K1 was associated with Luminal A status, low grade histology and low proliferation rates whereas mutant TP53 associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon AI treatment. Pathway analysis demonstrated mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in ER+ breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumor biology but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

The use of sentinel lymph node surgery after neoadjuvant chemotherapy for patients who present with cN1 breast cancer provides an opportunity to avoid axillary lymph node dissection for those patients who have eradication of their nodal disease with chemotherapy. Since the initial publication of prospective trials demonstrating the false-negative rate of sentinel lymph node (SLN) surgery in this setting, this practice has been increasing. [1][2][3][4] A recent survey of the American Society of Breast Surgeons (ASBrS) reported that 85% of respondents offered SLN surgery to some patients in this setting. 5