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Annals of Surgical Oncology

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01.07.2009 | Breast Oncology

Genetics and Personal Genomics for Personalized Breast Cancer Surgery: Progress and Challenges in Research and Clinical Practice

verfasst von: Dimosthenis Ziogas, MD, Dimitrios H. Roukos, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 7/2009

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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.

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Titel: Genetics and Personal Genomics for Personalized Breast Cancer Surgery: Progress and Challenges in Research and Clinical Practice
verfasst von: Dimosthenis Ziogas, MD
Dimitrios H. Roukos, MD
Publikationsdatum: 01.07.2009
Verlag: Springer-Verlag
Erschienen in: Annals of Surgical Oncology / Ausgabe 7/2009
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-009-0436-2

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Abstract

Background

Objective

Data sources and synthesis

Results

Conclusions

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