Mastectomy vs. Preventative Screening for Woman Diagnosed with the BRCA1/2 gene

Written by Jasmine Hardie

  Introduction

In this literature review a critique of evidence will be presented, discussing whether a positive test result of the BRCA mutation effects whether woman would choose a surgical intervention of prophylactic mastectomy or rather to comply with regular breast screening as well as self examinations throughout their lifetime. This is a significant topic as breast cancer is one of New Zealand and the world’s most common form of cancer with significantly high mortality rates (Ministry of Health, 2015). However, if found early enough, appropriate measures can be taken to reduce the risk of death. Throughout this review I have been able to explore a major test available, this being genetic testing for the BRCA mutations and the impact that this has on an individual’s decision of risk reducing intervention. As breast cancer is one of the most common cancers in the world, there is momentous amount of emotional distress involved with this cancer, therefore it is intriguing as to the why measures such as genetic testing are able to be completed to reduce this distress worldwide however are not so prevalent when discussing cancer risks (Ministry of Health 2015). The following question was structured to allow myself to critically review best evidence relating to appropriate clinical practice. “Is double mastectomy’s the safest option for women at high risk of developing breast cancer?”

  Rationale

Breast cancer is one of the most common malignancies in the world for woman. There is a lifetime risk of 10% (King, Marks, Mandell, 2003). It is also New Zealand’s third most diagnosed cancer, being responsible for more than 600 deaths yearly (Ministry of Health, 2015). Testing for the BRCA1 and BRCA 2 mutation allows individuals who meet the criteria or are generally concerned due to personal or family history a chance to consider and research the advantages and disadvantages of preventative measures such as prophylactic mastectomies or regular screening along with thorough regular physical examinations (O’Neill et al, 2010). Many woman have a family history of breast and ovarian cancer, which makes them more susceptible to developing breast or ovarian cancer in the future however are unaware of this and continue living their lives with no concern. Genetic testing is able to inform an individual whether they have inherited either BRCA gene, and therefore are able to make decisions (Roukos, & Briasoulis, 2007).

  The BRCA gene

The best example of what is deemed a high-risk woman of developing breast cancer is a woman who has inherited the BRCA1/2 mutation. BRCA1 and BRCA2 are genes, which are tumour suppressor genes as they produce tumour suppressor proteins. The role of these proteins is to stabilise the cells genetic material by ensuring that all damaged DNA is rapidly repaired in adequate time (National Cancer Institute, 2015). When these genes are mutated, this means that the protein product either does not function correctly or is not created at all and therefore means damaged DNA is unable to properly repair. This mutation in the genes results in the likelihood of the cells developing further genetic alterations that can further lead to cancer malignancies (National Cancer Institute, 2015). Since the first discovery of the BRCA genes, over 5000 singular alike mutations in these genes have been identified. Although the BRCA genes are more likely to be found in individuals with a significant family history of breast cancer, for the general population these mutations are only estimated to effect 0.1%. Testing for the BRCA1 and BRCA 2 mutation allows individuals who meet the criteria or are generally concerned due to personal or family history a chance to consider and research the advantages and disadvantages of preventative measures such as prophylactic mastectomies or regular screening along with thorough regular physical examinations (O’Neill et al 2010).

Being a carrier of either BRCA genes increases an individual’s lifetime risk of developing breast cancer to 80% (Roukos, & Briasoilis, 2007). Comparing this data  to the general populations risk of 10% shows how important it is for woman who are believed to be high risk of this mutation to get genetically tested (Roukos, & Briasoulis, 2007).  Ideally this genetic testing should be available for all woman who are deemed high risk, however since there is such a low prevalence of this mutation in the general population and taking into consideration cost factors, this widely decreases the amount of genetic testing offered. Testing of the mutation is recommended if a direct family member has also been diagnosed with carrying the BRCA mutation. If there is no direct family member known to have the BRCA mutation due to lack of testing, however the individual is still deemed to be high risk due to significant familial and/or personal history of breast cancer, then personal genetic testing remains to be recommended (Roukos, & Briasoulis, 2007).

As woman who test positive for the BRCA1 or 2 mutation are deemed high risk for developing breast cancer in their future years, they then face a number of decisions regarding what they are able to do in regards to this higher risk (O’Niell et al, 2010). One of the options available for woman who have tested positive for either BRCA genes is to undergo a prophylactic mastectomy. This has been shown to reduce the risk of developing breast cancer by 95% in woman who have inherited the disease causing mutation as well as up to 90% for woman who have a significant family history of breast cancer (Hartmann et al, 1999). 

  Influences regarding interventions

One significant factor which influenced women’s perceptions on which risk prevention intervention was more desirable was cost factor. Although in New Zealand screening for breast cancer is free, in many other countries of the world, without adequate health insurance these procedures can cost thousands of dollars if regular check-ups are completed as recommended over several years (Grann et al, 2010). It also becomes more difficult for woman who have been diagnosed with the BRCA mutation to complete regular screenings with more sensitive MRIs as recommended. For example, in the USA a MRI can cost approximately ten times the amount of a mammogram alone (Grann et al, 2010). If the MRI testing for breast cancer cost was reduced by 30% then it could be deemed cost effective for woman wanting to prevent their risk as best as possible. However since it is not reduced, this means that the ideal strategy concluded for BRCA1 and BRCA2 carriers was prophylactic surgery as it is the least expensive with the highest rate of effectiveness (Grann et al, 2010). Cost factor is one of the only outcomes, which remained the same for every individual compared to other outcomes such as quality of life, or life expectancy, which can be completely different, varying between an individuals lifestyle circumstances (Grann et al, 2010).

Another factor, which affects a woman’s choice in preventive measures, was the woman’s age. If choosing to undergo prophylactic surgical intervention, then this is recommended to be completed as soon as possible. This is due to the aggressiveness and early onset of cancer in carriers of the BRCA mutation. Completing the surgery before the age of 40 is shown to reduce the risk of the breast cancer occurring according to a large descriptive study (Roukos, & Briasoulis, 2007). This information is also backed by evidence found from another study completed by the clinical genetics research program in the Lombardi Comprehensive Cancer Centre where it was found that many younger participants opted to complete prophylactic mastectomies as they understood they had a higher lifetime risk of developing breast cancer compared to the older participants above the age of 40 (Schwartz et al, 2012).

  Genetic test results

However prophylactic mastectomies are not always the best option. Woman who tested negative or uninformative for the BRCA genes were much more likely to opt not for preventative surgery, rather complete regular screening instead. Uninformative BRCA test results are the most common in practice and are connected to difficult to quantify and heterogeneous breast cancer risks (Schwatz et al, 2012). Uninformative negative results refer to when a family has significant history with numerous diagnosis of breast/and or ovarian cancer however no member of that family test positive for the BRCA mutation. As none of the members have tested positive, this means that there is no new evidence found about themselves and their family members risk of cancer as the mutation deemed to be the cause of cancer in the family has not been identified (Dijk et al, 2005).

In summary, the literature reviewed clearly shows out of the many options available for high-risk woman, prophylactic mastectomy appears to be the best option in regards to woman who test positive for BRCA genes as it is the most cost effective with the safest outcome.

  Implications on practice

After critically analysing the above literature, it can be found that since a persons BRCA genetic result are able to vary ranging from positive, negative and uninformative test results then this also means that these individuals will have very different perceptions on which post testing intervention is most appropriate. An individual who tests negative for the BRCA genetic mutation may not be at any lesser risk of developing breast cancer in the future however are just unaware of this risk as the results have not identified any hereditary mutation.

Therefore relating back to clinical practice, it is clear to see that whatever risk prevention strategy chosen regardless of test results relies solely on an individual’s perception of wellbeing. Individuals who received positive genetic results had a higher chance of choosing to undergo a prophylactic mastectomy due to the higher percentage of risk reduction, that being 90% (Hartmann et al, 1999). Any individual who undergoes this treatment option will need to be cared for with the upmost respect. Although these individuals should have completed pre surgical counselling regarding this procedure, the individuals can be very emotional as the procedure is very invasive, and it is an immense change in the way the individual will now see themselves (O’Neill et al, 2010).

For the BRCA mutation genetic testing to be more widely known, more education around what it is and how it can potentially save a life is needed. All literature reviewed above discusses woman who had already known about genetic testing due to education provided by healthcare professionals. However, for every woman who does know the advantages of completing genetic testing if deemed high risk, there are also multiple woman who do not (Obesity Fitness and Wellness, 2004). If more woman know about the tests available then more woman will be able to be diagnosed at an earlier age giving them more time to decide on treatment options and lessen the chance of passing away of breast cancer in the future.

Importantly it should also be remembered that not all hereditary forms of breast cancer are due to BRCA1 or BRCA2 mutations (Centers for Disease Control and Prevention, 2015). Breast cancer in the general population is mainly due to somatic mutations in the breast cells developed throughout a person’s lifetime. These mutations do not cluster in families and therefore there is no hereditary impact, thus no extremes preventative measures can be taken in such of BRCA mutations (Genetics Home Reference, 2016).

  Recommendations and rationale related to practice

From this literature review I have been able to construct two appropriate recommendations in which I believe will be beneficial for woman who tested positive for either of the BRCA genes, in deciding which if any preventative measure should be taken. These recommendations are:

  1. For the Ministry of Health to be able to offer all individuals with a higher risk of developing breast cancer due to significant familial history free BRCA mutation testing. Doing this would considerably reduce the amount deaths per year due to hereditary breast cancer. Genetic testing is not something that is done as a spur of the moment decision and takes a lot of consideration, as for some the idea of knowing whether or not they have either BRCA mutation is not ideal. However there are many individuals in the world who do believe they are at high risk of having the BRCA mutation however are unable to afford the testing as well as the interventions that may take place post testing. Depending on the type of test required due to different risk factors, the cost of genetic testing can range from several hundred dollars to several thousand (National Cancer Institute, 2015). With more people being able to afford testing, this would mean more people who are willing to accept the testing are able to do what they like with this new knowledge and potentially able to decrease the risk of developing breast cancer in the future.
  2. The second recommendation is that it should be compulsory to attend genetic counselling prior to completing the BRCA genetic testing as well as after. I believe in this recommendation as the literature reviewed has shown great evidence to suggest that the there may be associated psychological distress related to the choice of whether to complete genetic testing or not. This uncertainty related to testing is mainly due to the fear and anxiety that a positive result could dramatically impact their quality of life. Although genetic counselling can not fully diminish these anxieties, many times being fully informed of options and support can significantly reduce the anxiety of testing (Berry, Parmigiani, Sanchez, & Schildkraut, 1997). Genetic counselling is not only important for prior to genetic testing but also has significant impact of how consumers are able to react to results post testing. A genetic counselling session is carried out by a healthcare professional that is experienced in cancer genetics. This enables consumers to feel comfortable knowing they are receiving the most evidence based care possible (National Cancer Institute, 2015). Genetic counselling disclosure sessions are where the test results and associated implications are discussed. Common implications include associated breast cancer risks, suitable options for prevention depending on the person, surveillance, possible psychological deficits related to conclusion of results and referrals to appropriate healthcare professionals for recommended follow-ups (O’Neill et al, 2010). Making these genetic counselling sessions compulsory for individuals completing the BRCA genetic testing means more informed consumers meaning a lesser risk of harmful emotional distress when receiving results.
  Conclusion

In conclusion, after an in depth and critical review of available literature surrounding choices of risk prevention for woman at high risk of breast cancer, it is clear to see that the majority of the literature suggests that prophylactic mastectomies are the optimal option after receiving positive BRCA genetic results. Prophylactic mastectomies reduced the risk of developing breast cancer for woman who had inherited the BRCA genetic mutation by up to 90% thus making it ‘safer’ then regular screening where a metastasising malignancy can always be missed. Also, regular MRI’s are thought to be too expensive for individuals especially in countries such as the USA where it can cost thousands of dollars without adequate insurance. Therefore it is clear to see that when a woman has been disclosed with a positive BRCA result she is then d

  References

Berry, D. A., Parmigiani, G., Sanchez, J., Schildkraut, J., & Winer, E. (1997). Probability of Carrying a Mutation of Breast-Ovarian Cancer Gene BRCA1 Based on Family History. JNCI Journal of the National Cancer Institute,89(3), 227-237. Doi: 10.1093/jnci/89.3.227

Centers for Disease Control and Prevention. (2015). Does Breast or Ovarian Cancer Run in Your Family. Retrieved from http://www.cdc.gov/features/hereditarycancer/

Dijk, S. V., Otten, W., Timmermans, D. R., Asperen, C. J., Meijers-Heijboer, H., Tibben, A., Breuning, M., & Kievit, J. (2005). What’s the message? Interpretation of an uninformative BRCA1/2 test result for women at risk of familial breast cancer. Genetics in Medicine Genet Med,7(4), 239-245. Doi: 10.1097/01.gim.0000159902.34833.26 

Genetics Home Reference. (2016). Breast Cancer. Retrieved from https://ghr.nlm.nih.gov/condition/breast-cancer

Grann, V., Patel, P., Jacobson, J., Warner, E., Heitjan, D., Ashby-Thompson, M., Hershman, D., & Neugut, A. (2010). Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat Breast Cancer Research and Treatment,125(3), 837-847. Doi: 10.1007/s10549-010-1043-4

Hartmann, L, Schaid, D., Woods, J., Crotty, T., Myers, J., Arnold, P., Petty, P., Sellers, T., Johnson, J., McDonnell, S., Frost, M., & Jenkins, R. (1999). Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer. Obstetrical & Gynecological Survey,54(6), 381-383. Doi: 10.1097/00006254-199906000-00017

Litton, J., Westin, S., Ready, K., Sun, C., Peterson, S., Merc-Bernstam, F., Gonzalez-Angulo, A., Bodurka, D., Lu, K., Hortobagyl, G., & Arun, B. (2009). Perception of screening and risk reduction surgeries in patients tested for BRCA deleterious mutation, Cancer, 115(8), 1598-1604. Doi: 10.1002/cncr.24199

King, M., Marks, J., & Mandell, J. (2003). Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science,302(5645), 643-646. Doi: 10.1126/science.1088759

Ministry of Health. 2015. Breast Cancer. Retrieved from http://www.health.govt.nz/your-health/conditions-and-treatments/diseases-and-illnesses/breast-cancer

National Cancer Institute. (2015). BRCA1 & BRCA2: Cancer Risk & Genetic Testing. Retrieved from http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#q1

National Cancer Institute. (2015). Should people considering genetic testing for BRCA1 and BRCA2 mutations talk with a genetic counselor?. Retrieved from http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#q7

Obesity Fitness and Wellness. (2004). Cancer Screening; More research, education about complexities of BRCA1/2 genetic testing, Trade Journals. 211(1), 1.

O’Neill, S., Valdimarsdottir, H., Demarco, T., Peshkin, B., Graves, K., Brown, K., Hurley, K., Isaacs, C., Hecker, S., & Schwartz, M. (2010). BRCA1/2 test results impact risk management attitudes, intentions, and uptake. Breast Cancer Res Treat Breast Cancer Research and Treatment,124(3), 755-764. Doi: 10.1038/ncponc0930

Roukos, D. H., & Briasoulis, E. (2007). Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome. Nature Clinical Practice Oncology,4(10), 578-590. Doi: 10.1038/ncponc0930

Schwartz, M., Isaacs, C., Graves, K., Poggi, E., Peshkin, B., Gell, C., Finch, C., Kelly, S., Taylor, K., & Perley, L. (2011). Long-term outcomes of BRCA1/BRCA2 testing: Risk reduction and surveillance. Cancer,118(2), 510-517. Doi: 10.1002/cncr.26294