Genetics and genome-wide association studies: surgery-guided algorithm and promise for future breast cancer personalized surgery

Abstract

Although personalized medicine and oncology in clinical practice is still a dream, some isolated first steps have been taken. Effective preventive and therapeutic interventions are now tailored in some individual breast cancer patients on the basis of BRCA, estrogen receptor and HER2 status. Personal genome-wide tests hold rational promise toward a true personalized management. The recent dramatic increase of more aggressive surgery by 150% in the USA is effective for preventing local recurrence and contralateral breast cancer but represents a surgical overtreatment that may harm patients and health systems. This article is based on three subpopulations: familial BRCA-positive patients and BRCA-negative patients, and sporadic breast cancer patients. Combining established classic and new risk factors, including familial BRCA susceptibility to breast cancer, an integrated surgery-guided algorithm for clinical validity is proposed. Future genome-wide association studies larger than those currently available using newer genotyping platforms with more than 1 million single-nucleotide polymorphisms and copy number variants will complete the genetic map. Due to the small effects of all these risk variants, further functional studies to explore the intracellular interactions of these variants and signaling pathways networks will be required. Ultimately, large, prospective, population-based studies recording family and medical history and genetic and environmental risk factors will lead to true personalized breast cancer local control.

Keywords::

• breast cancer
• genetics
• genome-wide association study
• genomics
• personalized medicine
• surgery

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.