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The care of breast cancer predisposition gene mutation carriers.

In this issue of Advances in Breast Cancer we are privileged to have three eminent specialists review the genetic basis of high-risk breast cancer predisposition genes and the status of two aspects of risk-reduction surgery: risk-reducing mastectomies in gene mutation carriers who are well and the management of the contralateral breast in cancer-affected carriers.

Professor Gareth Evans reviews the current understanding of high-risk predisposition gene carriers and puts in context the role played by high-penetrant autosomal dominant genes in breast cancer aetiology. There is developing interest in polygenic low-penetrant genes that may be influenced by environmental factors, although the actual contribution of such genes to breast cancer pathogenesis remains elusive. The majority of gene carriers have either a BRCA1 or BRCA2 mutation, but a helpful table in this article summarises the role of TP53, ATM, PTEN and CHEK2.

Mr Andrew Baildam reviews the role of risk-reducing mastectomy as the only practical means of cancer prevention in this high-risk group of breast cancer predisposition gene carriers. Risk-reduction rates, as a result of prophylactic mastectomy, are confirmed to be in excess of 90% in a recent publication reporting the experience of 10 centres that regularly practise risk-reducing mastectomy [1]. This publication is important because of the contribution by multiple centres with clinical practice arrangements, risk assessment and surgical techniques that are applicable to those that we are familiar with today rather than from outdated concepts and techniques from the past. The importance of multidisciplinary team-working in specialised units that offer risk-reducing mastectomy is an important message; pitfalls that betide the novice or occasional risk-reducing mastectomy surgeon should not go unheeded. The details of the surgical techniques, and the in-depth assessment for case selection, lie outside the remit of this issue of Advances in Breast Cancer, but an elegant summary is provided.

Mr John Benson summarises the evidence base for recommendations on how to manage the contralateral breast in an affected carrier with a high-risk predisposition mutation diagnosed with unilateral breast cancer. This is often a vexing question, as many young patients, sometimes with an extremely strong family history of breast cancer, may not have a proven gene-carrier status at the time of breast cancer diagnosis. Management of the contralateral breast at the time of cancer management of the index breast often adds another dimension to the decision-making with an array of further information on diagnosis and treatment options, in addition to coping with the prolonged multimodal treatment of breast cancer. The contralateral breast nevertheless remains at risk in high-risk predisposition gene carriers. A negative gene test in such individuals is at best uninformative and the contralateral breast needs to be managed as high risk even in the absence of a recognised high-risk predisposition gene.

Breast conservation surgery remains an option in many cases of breast cancer diagnosed in high-risk predisposition gene carriers. Randomised clinical trial data will never be available to provide the answers to many existing questions and difficulties in interpreting the current literature are recognised. In the USA, the popularity of contralateral risk-reduction mastectomy even for early-stage breast cancer is rising dramatically. Careful patient counselling and caution should be exercised in the absence of strong data to define relative cut-off values on which contralateral risk-reducing surgery should be recommended rather than offered, or indeed agreed to upon patient request. The competing risks of risk-reduction compared to the real threat of the established cancer in the index breast needs to be considered and patient understanding ensured. Many patients, particularly those with a strong family link and with an established high-risk predisposition gene, have a clear view of their management when their own breast cancer diagnosis is made. In the presence of a known high-risk predisposition gene within the family, a rapid test to determine the carrier status of the affected individual at the time of diagnosis may be possible.

Technology to correct genetic defects in vivo is unlikely in the foreseeable future and there has been much media publicity about a recent case of embryo selection. High-risk predisposition genes account for a small proportion of the total number of breast cancers diagnosed. The overall care of breast cancer predisposition gene mutation carriers is complex and needs to be patient focused. Multidisciplinary team management comes to the fore in managing these patients to individualise recommendations, the implications of which are far reaching within the affected family and ongoing care is often long term.


[1.] Evans G, Baildam A, Brain A et al. Risk-reducing mastectomy: outcomes in 10 European Centres. J Med Genet, epub 7 Nov 2008; doi:10.1136/jmg.2008.062232.

Gerald Gui

Academic Surgery (Breast Unit), The Royal Marsden NHS Trust, London, UK
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Author:Gui, Gerald
Publication:Advances in Breast Cancer
Article Type:Editorial
Geographic Code:4EUUK
Date:Mar 1, 2009
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