GENETIC COUNSELING OF BREAST CANCER
Genetic counseling for women with a family history of breast cancer requires an initial assessment of their lifetime risk of developing breast cancer on the basis of empirical data derived from taking a family history that includes information about cancer type and age at onset in all first-degree and second- degree relatives and as many more distant relatives as possible. It is important to try and confirm diagnoses if it will make a material difference to the clinical decisions made. Risk estimates can be obtained using epidemiological data, or with the help of computer programs which calculate risks using these data, and can be expressed as a lifetime risk or as a risk for developing cancer over a shorter time period, such as the ensuing 10 years (Antoniou et al. 2004). Programs such as IBIS and BRCAPRO can also calculate the probability of being a BRCA1/2 mutation carrier, although IBIS is limited to unaffected women. Hand-scoring, non-Bayesian methods, such as the Manchester scoring system have the benefit of simplicity and user- friendliness, relying on a scoring system for the numbers of affected relatives. They avoid the need for a computer program (Evans et al. 2004). Screening guidelines based on family history and genetic testing are available on the NICE website, http://www.nice.org.uk/cg41: “Familial breast cancer: the classification and care of women at risk of familial breast cancer in primary, secondary and tertiary care (partial update of CG14)”.
A woman whose mother has a germline breast cancer susceptibility mutation has a prior risk of 50 % of inheriting the susceptibility, so that her lifetime risk of developing breast cancer is about 40 % (assuming 80 % gene penetrance for breast cancer). However, if she remains healthy after the age of 50 years, her actual risk will have fallen because she has lived through a substantial amount of her risk period, with most hereditary breast cancer occurring at a younger age. The risk that the daughter of a gene carrier who remains unaffected at 50 years of age has inherited the susceptibility has fallen to approximately one-third, and if she remains healthy, it is less likely that she has inherited the susceptibility the older she becomes.
The probability that the family is segregating for a BRCA1 or BRCA2 germline mutation may be derived from family history data, in order to give an indication as to the likelihood that the consultant could be offered a predictive test for such a mutation. This chance is very dependent on age at diagnosis in the affected woman (there is a 17 % chance of a BRCA1 mutation in breast cancer families with average age at diagnosis below 35 years, but a 1 % chance when the average age at diagnosis is over 59 years). A family history of ovarian cancer increases the chance of finding a BRCA1 mutation, as does multiple primary breast or ovarian cancers in an affected woman of Ashkenazi Jewish origin (Couch et al. 1997).
The original model for counseling and genetic testing of women desiring and eligible for genetic testing includes a lengthy initial counseling, where the risks and benefits of genetic testing are fully discussed, with due attention being paid to all the implications of a positive or negative test result being discussed before testing, with offers of psychological support. Options for prophylactic and surveillance interventions should be discussed in detail before the test is undertaken, with additional discussions about insurance and employment issues. One of the premises of this model is that many potential psychological sequelae of predictive testing exist, particularly in relation to psychiatric morbidity. Additionally, any effect on uptake of surveillance and prophylactic measures required careful consideration (van Oostrom et al. 2003). These procedures were put in place partly because the detection of a germline BRCA1 or BRCA2 mutation in an affected woman can be of great psychological impact and was considered by some to be possibly equivalent to the shock of the original cancer diagnosis. In addition, detailed counseling would need to cover the possibility of identifying a germline mutation of uncertain significance, especially in population groups that have not been extensively sampled.
This traditional model is the most common context in which women receive genetic testing. More recently, however, population-based testing of unaffected women without detailed counseling has been carried out (Metcalfe et al. 2010). While long-term sequelae are not known, short-term data do not suggest harm (Metcalfe et al. 2012). Clearly, testing before a cancer diagnosis is optimal if the “risks of knowledge” and negative effects of surgical intervention (e.g., preventive oophorectomy) are outweighed by the decrease in cancer incidence. It will not be possible to know this without long-term follow-up. Nevertheless, if the initial treatment of women with breast cancer could be significantly and positively influenced by knowledge of mutation status at the time of diagnosis, then the benefit of rapid, low-cost, tailored genetic testing may be greater than the risks of harm resulting from a more limited pretest counseling. Early studies involving full counseling have suggested that affected women who learn they are carriers at the time of diagnosis or soon afterwards tend to make different surgical decisions than those who find out later (Schwartz et al. 2004, 2005); thus, there is at least precedent for considering testing at the time of diagnosis.