In summary, the identification of a germline BRCA mutation in a woman with breast or ovarian cancer should not, at present, influence her local or systemic treatment. The recognition of a hereditary breast or ovarian cancer, however, indicates the need for specialized surveillance and prevention strategies to manage subsequent cancer risk in that woman and in her female relatives.
Males in such families may also benefit from heightened surveillance for colon, prostate and possibly breast cancer. The choice of whether or not to undergo genetic testing is a difficult one and should only be made after genetic counseling by a qualified professional.
Such professionals should also be involved in the interpretation of genetic test results. Such expertise is necessary because the integration of test results into a cancer risk assessment is a complex endeavor, particularly if results are “negative” in the setting of a strong family history or if the results are ambiguous (genetic variants of uncertain significance).
Although the feared social risks of genetic testing appear not to have materialized in any systematic way, the psychosocial consequences and impact upon family dynamics are important considerations that are still being defined. Finally, the medical management of individuals at highest hereditary risk is being continuously refined. A new era of genetically targeted risk management has dawned, and much research is required to maximize the benefits of this technology for families at risk.
We have recently published an evaluation of 305 unselected women of Ashkenazi descent undergoing breast-conservation therapy for a total of 329 invasive breast cancers.
Using an anonymized design, outcomes of 28 women with founder mutations in BRCA1 or BRCA2 were compared to those of women without mutations. Overall, women with mutations fared poorer than those without, with 10 year breast-cancer-specific survival of 71.9% compared to 87.2% in those without. After adjustment for tumor size and nodal status, however, mutation status was not an independent predictor of worse survival. These results, using a study design that avoids the survival biases inherent in other series, suggest that women with certain specific BRCA mutations tend to present at a more advanced stage than women without such mutations, although it remains unclear if this tendency for more advanced presentation is a result of a lack of screening among younger women or a consequence of a more aggressive biology.
Mark E. Robson
Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 2003
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