In the United States, approximately 12.8% of women will be diagnosed with breast cancer at some point in their lifetime. If the cancer is caught early before it has spread to other tissues, the chances of surviving five years after diagnosis is 98.8%. If the cancer is diagnosed after it has been metastasized, the 5- year survival rate dwindles down to 27.4%, underscoring the importance of early detection.
Genetic testing gained mainstream traction in recent years through the popularization of companies such as 23andMe® and Ancestry®. In reality, genetic testing has been available as a powerful diagnostic tool for hereditary cancer, such as breast cancer, since the 1990s. In fact, the U.S. Preventive Services Task Force (USPSTF) recommends genetic screening for BRCA mutations in women with a family history of potentially harmful BRCA mutations. The BRCA1 and BRCA2 genes are tumor suppressor genes and individuals with BRCA mutations have an up to 20-fold increased risk for early-onset breast cancer. Identification of deleterious BRCA mutations provides individuals with therapeutic options to reduce the risk of developing cancer and allows for early cancer detection. Some individuals with know BRCA mutations may opt for chemoprevention drugs (i.e. tamoxifen citrate, raloxifene hydrochloride) or mastectomies to decrease their risk of developing breast cancer. One study with 2,482 women with BRCA 1/2 mutations showed no incidences of breast cancer in women who undergone risk-reducing mastectomy (RRM). In comparison, of the women without RRM, 7% were diagnosed with breast cancer. Additionally, improved surveillance in the form of increased number of mammograms and clinical breast examinations allows for early cancer detection, which increases the chances of treatment success. Genetic counseling generally accompanies genetic testing and are performed by physicians or non-physicians trained in medical genetics and counseling . The role genetic counselor is to guide the patients in (1) understanding the pros, cons, and limitations of genetic testing; (2) understanding the test results and making an informed decision; and (3) identifying strategies to reduce the risk of cancer .
Although the benefits of genetic screening for BRCA mutations in high-risk women are many, the net benefit of genetic screening in women without familial history of potentially harmful BRCA mutations is minimal to potentially harmful. The USPSTF recommends against BRCA testing for women with no family history of harmful BRCA mutations . This may be due to the psychosocial aspect of genetic testing as females identified to carry the BRCA mutations are shown to have increased cancer- related worries than non-carrying females. The same study showed 28% of BRCA mutation carriers to have undergone bilateral risk- reducing mastectomy within 12- months of testing . Given that increased genetic susceptibility does not always translate to cancer development, subjecting low-risk individuals to unnecessary worries and surgeries may proved to be more harmful than beneficial.
Although genetic testing is a powerful tool in assessing the cancer risk, it has many limitations. For one, testing negative for BRCA mutations does not equate to having no genetic susceptibility for cancer development. In fact, many non- BRCA genes mutations have been identified to be associated with hereditary cancer and many more are still left undefined. In one study, 1046 individuals lacking BRAC 1/2 mutation underwent a 29- or 25- gene multi-gene panel genetic testing. Of those participants, 3.8% were found to harbor deleterious mutations in genes associated with increased cancer susceptibility . Furthermore, cancer is a multifactorial disorder that is affected by factors such as environmental exposure (i.e. exposure to radiation), life- style (i.e. diet and tobacco use), and biology (i.e. age and gender). Therefore, focusing solely on genetics will not provide a comprehensive assessment of cancer risk. Although the cost of genetic testing has decreased with the continual emergence of new technology, as of 2010, BRAC1/2 testing cost approximately $400-$500 and more comprehensive sequencing could cost up to $3000 .
For individuals that are at high-risk for breast cancer, it may be good to discuss the pros and cons of genetic testing with a physician and genetic counselor.
- American Cancer Society. Survival Rates for Breast Cancer. September 20, 2019.
- Moyer, V.A., Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med, 2014. 160(4): p. 271-81.
- Scheuer, L., et al., Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol, 2002. 20(5): p. 1260-8.
- Valencia, O.M., et al., The Role of Genetic Testing in Patients With Breast Cancer: A Review. JAMA Surg, 2017. 152(6): p. 589-594.
- Domchek, S.M., et al., Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. Jama, 2010. 304(9): p. 967-75.
- Watson, M., et al., Psychosocial impact of breast/ovarian (BRCA1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort. Br J Cancer, 2004. 91(10): p. 1787-94.
- Desmond, A., et al., Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. JAMA Oncol, 2015. 1(7): p. 943-51.