Genetic Predisposition to Breast Cancer: when public awareness demands clarity

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By Dr. Luis Costa, Director of Oncology at Santa Maria Hospital, Lisbon.

 Ever since last May, a great deal of attention has been focused on news that the actress Angelina Jolie underwent a preventive bilateral mastectomy after learning that she was a carrier of a pathogenic gene mutation (1) known to be responsible for a higher incidence of breast and/or ovarian cancer.

Among the many media messages emerging from Jolie’s revelation was that carriers of such a mutation should consider preventive surgery and that non-carriers could rest easy that they were in a lower risk category. While these messages have opened up useful opportunities for dialogue between a woman and her doctor, the truth behind genetic testing is much more complex. 

Women who have a heritable BRAC1 or BRAC2 gene mutation such as Jolie’s bear the same characteristic or genetic defect that gives them a higher genetic susceptibility to cancer. Research into these mutations has been of incredible valuable in identifying women who may benefit from certain preventive measures.

Indeed, once found to be carriers, patients’ relatives can be also screened and can then make informed decisions as to precautionary strategies going forward.

Yet not only does a genetic predisposition for breast cancer represent only an average of 5% of all cases but the cumulative lifetime risk of cancer varies between 15% and 85%. It is also important to remember that the absence of a BRAC1 or BRAC2 genetic mutation does not necessarily mean that a woman is not at high risk for breast cancer, as is the case with women suffering from breast cancer at a young age with a family history of the disease but not showing any mutation. In the future, these cases may perhaps be explained by new mutations that are not yet specifically recognized as pathogenic mutations.

In terms of genetic screening itself, certain criteria in a woman’s clinical history can be used to determine whether she should be referred for genetic consultation. Some criteria are obvious, such as a personal history of breast cancer at a young age or a history of breast and ovarian cancer in an immediate relative.

At other times, however, clinical history is not as suggestive but may nevertheless meet criteria for genetic testing, such as the example of a young woman suffering from an aggressive type of breast cancer known as “Triple Negative” but with no known instances of cancer in her family.

Finally, before going ahead with genetic testing, it is essential that women with breast cancer and their relatives be equipped with all of the information available from reliable, supportive sources, including psychological evaluation and support. Where a pathogenic mutation is detected, women can choose from a broad spectrum of treatment options, from intensive surveillance to hormonal treatment to preventive breast and/or ovarian surgery.

The public awareness created by Angelina Jolie’s decision should therefore be seen as an opportunity to help those women who are carriers of the mutation, as in Jolie’s case, to seek accurate information and advice when they too are facing difficult yet crucial decisions.

1. Ford D, Easton DF, Stratton M, et al: Genetic heterogeneity and penetrance analysis of the
BRCA1 and BRCA2 genes in breast cancer families: The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676-689, 1998

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