Genetics and personal genomics for personalized breast cancer surgery: progress and challenges in research and clinical practice

Abstract

Background: The age of personal genomics is here. A flood of translational research discoveries may influence also surgeon oncologist. Breast-conserving surgery (BCS) is standard care in early breast cancer. Classic clinicopathologic factors are suboptimal to predict risk of ipsilateral breast cancer (IBC) recurrence and/or contralateral breast cancer (CBC). Human genetic variation may be involved in local failures.

Objective: To describe the potential clinical utility of genetics, personal genomics, and epigenetics to identify IBC/CBC high-risk patients who might benefit from aggressive surgery (bilateral mastectomy).

Data sources and synthesis: PubMed (MEDLINE) was searched (January 1990 to November 2008).

Results: Even following current guidelines, IBC/CBC as isolated first event in a long-term aspect after treatment suggests a serious problem. Preclinical and clinical data reveal that at highest risk of IBC/CBC are patients with inherited BRCA1/2 mutations who benefited from bilateral mastectomy. Local failure risk prediction is currently unfeasible among familial non-BRCA1/2 (BRCA-test negative) and sporadic (no family history) breast cancer. Genome-wide association studies have already identified novel risk alleles with a series of tumor-initiating single-nucleotide polymorphisms (SNPs). Some of these variants and other novel SNPs and copy-number variants (CNVs) may also be relevant for local failures (IBC/CBC).

Conclusions: Beyond established risk factors, genetic testing allows identification of high-risk patients (BRCA mutation carriers) who may benefit from bilateral mastectomy rather than BCS. Human genetic variation (SNPs/CNVs) and DNA methylation may be relevant for local failures assessment. Technological revolution has opened a new avenue but multiple challenges should be overcome to integrate SNPs/CNVs as markers for IBC/CBC risk-stratification-based personalized surgery.