The concept of genetic testing and personalised medicine has recently been brought to the media’s attention by the actress Angelina Jolie following her choice to undergo a double mastectomy as a preventive medical procedure based on genetic testing. Angelina was found to carry the mutant form of BRCA1, which predicts a personal risk to breast cancer of more than 85% during a woman’s lifetime. According to the American National Cancer Institute, a woman with a BRCA 1 gene mutation is 5 times more likely to develop breast cancer than a woman without this mutation and anywhere between 11 to 36 percent more likely to develop ovarian cancer. Mutations in the BRCA1 gene may also increase a woman’s risk of developing uterine, cervical, colon and pancreatic cancer. However, if we look into the history of the BRCA 1 mutations and cancer risk, we find that before 1940, the risk was 24% as compared to the current 82% risk.
This issue gives rise to some important questions: what has resulted in the same genetic set of characteristics for breast cancer incidence going from 24% in 1940 to 85% in 2013? How does this view of genetic expression and the influence of the lifestyle and environment relate to the decision to have a bilateral mastectomy for the prevention of breast cancer? Furthermore, how do we know that a specific genetic factor is being “translated” in the individual into an eventual disease early enough to do something about it?
To answer this and other questions, a roundtable discussion was recently published in the peer reviewed publication ‘Consultant’. It featured a medical geneticist (Dr Wilson), a breast surgeon (Dr Rahman) and an internist (Dr Kaplan) who all refer to clinical case studies and share current medical options for the management and testing of breast and ovarian cancers. They note that the typical approach is to use clinical features that are surrogates for metastatic potential, such as tumour size, tumour grade, lymph node involvement and hormone receptor status, to determine the average 10-year risk.
However, the consensus between these panellists was that we have arrived at an important juncture in the treatment of breast cancer. We stand between the clinical-pathological paradigm, which has been dominant for several decades, and the emerging genomic paradigm.
As a promoter of personalised medicine, I believe that we cannot change our genes, but we can change the environment, diet and lifestyle that may encourage the genetic risk to be translated into cancer. There are literally hundreds of different biomarkers that are used to assess specific functions that relate to how genes are being expressed in response to lifestyle, diet and environment. It is through this type of analysis that physicians can develop a personalised program based on the understanding of the trajectory of health or disease in the individual aimed at reducing the risk of preventable disease and improving function.