Microscopic tumor foci in axillary lymph nodes may reveal the recurrence dynamics of breast cancer

Dear Editor,In early breast cancer,the prognostic value of the num-ber of macroscopically metastasized axillary nodes has been recognized in earlier reports[1].However,the impact of microscopic tumour cell deposits on the sur-vival outcome of early breast cancer patients is still debated[2].This issue has gained increasing attention since the implementation of sentinel node biopsy in axil-lary node staging for tailoring breast cancer treatments,and the status of the single resected node would deter-mine the clinical decision of whether or not to perform the axillary lymph node dissection[3].Moreover,this issue raises more questions on whether to administer primary or adjuvant systemic treatment for patients with lymph nodes bearing isolated tumour cells(pN0[i+])or micrometastases(pN1mi).Despite the wide debate on the clinical treatment dilemma encountered by early breast cancer patients with microscopic tumour cell deposits,the biology underlying different pathologi-cal presentations at microscopic level(pN0,pN0[i+],pN1mi)and the disease outcomes remain poorly known.In an attempt to shed some light on this topic,we have analyzed,in the context of dormancy-based metastasis development model[4],early breast cancer patients con-ventionally classified as pN0(tumour foci with largest diameter≤2 mm)[5]by systematically reassessing their tumor recurrence dynamics following primary tumour resection at a single institution.

Pharmacogenetic and pharmacogenomic discovery strategies

Genetic/genomic profiling at a single-patient level is expected to provide critical information for determining inter-individual drug toxicity and potential efficacy in cancer therapy.A better definition of cancer subtypes at a molecular level,may correspondingly complement such pharmacogenetic and pharmacogenomic approaches,for more effective personalized treatments.Current pharmacogenetic/pharmacogenomic strategies are largely based on the identification of known polymorphisms,thus limiting the discovery of novel or rarer genetic variants.Recent improvements in cost and throughput of next generation sequencing(NGS)are now making whole-genome profiling a plausible alternative for clinical procedures.Beyond classical pharmacogenetic/pharmacogenomic traits for drug metabolism,NGS screening programs of cancer genomes may lead to the identification of novel cancer-driving mutations.These may not only constitute novel therapeutic targets,but also effector determinants for metabolic pathways linked to drug metabolism.An additional advantage is that cancer NGS profiling is now leading to discovering targetable mutations,e.g.,in glioblastomas and pancreatic cancers,which were originally discovered in other tumor types,thus allowing for effective repurposing of active drugs already on the market.