Alaska Pharmacists Association Continuing Education Home Study Series Program 0139-0000-19-201-H04-P/T Genetic Mutations in Quarterly AKPhA Newsletter Cancer: BRCA1 and Release Date 10/07/2019 Expiration Date 10/07/2022 BRCA2 CPE Hours: 2.0 (0.2 CEU) Authors: This lesson is a knowledge-based CPE activity Danielle Hess, PharmD Candidate 2020 and is targeted to pharmacists and technicians Anne Marie Bott, PharmD, BCOP, BCPS, in all practice settings. NCPS, Alaska Native Medical Center Learning Objectives Cancer is a genetic disease that results from an At the completion of this activity, the participant accumulation of mutations in genes that normally will be able to: control cellular growth. This accumulation of mutations 1. State two positive changes you can make to can arise from either somatic or germinal tissue. While your practice following participation in this the majority of mutations are somatic and result from series. environmental exposures, lifestyle, the aging process, or simply chance, germline mutations are inherited. These 2. Summarize three practice updates or changes inherited mutations in specific tumor suppressor genes you acquired while participating in this series. and DNA mismatch genes predispose individuals to 1 Disclosure various hereditary cancer syndromes. The author(s) and other individuals responsible for Of the tumor suppressor genes associated with inherited planning AKPhA continuing pharmacy education cancer syndromes, BRCA1 and BRCA2 play an activities have no relevant financial relationships to important role in the repair of damaged DNA and the disclose. stability of genetic material within cells. However, when these genes are mutated or altered, the DNA repair Fees process may not function properly, which causes cells to CE processing is free for AKPhA members. Non- be more prone to developing additional genetic members must submit $20 per quiz at: alterations that can lead to cancer. When an individual https://alaskapharmacy.org/payments/ carries a mutated BRCA1 or BRCA2 gene, their offspring have a 50% chance of inheriting the mutation. Although To Obtain CPE Credit for this lesson you must offspring may possess a normal second copy of the gene, complete the evaluation and quiz linked at the end the effects of mutations in BRCA1 and BRCA2 remain 2 and score a passing grade of 70% or higher. If you visible. score less than 70%, you may repeat the quiz once. CPE credit for successfully completed quizzes will In general, BRCA1 and BRCA2 gene mutations are the leading genetic factors for breast and ovarian cancers.2 be uploaded to CPE Monitor within 60 days. Most notably, these genes are the strongest susceptibility genes for breast cancer, as they are responsible for 90% of hereditary breast cancer cases. In addition, BRCA1 The Alaska Pharmacists Association is and BRCA2 are accountable for majority of hereditary 3 accredited by the Accreditation Council for ovarian cancer. When inherited, individuals tend to develop breast and ovarian cancer at younger ages than Pharmacy Education as a provider of continuing 2 those who do not possess these mutations. pharmacy education. Across the general population, 12% of women will develop breast cancer and 1.3% will develop ovarian cancer during their lifetime.4 In contrast, a recent study develop cancer. On the other hand, a negative result can aimed to estimate age-specific risks of breast, ovarian, be more difficult to interpret, as it is dependent on an and contralateral breast cancer for mutation carriers to individual’s family history of cancer and whether a evaluate risk modification by family cancer history and BRCA1 or BRCA2 mutation has been discovered in a mutation location. The resulting cohort of over 9,000 blood relative.2 mutation carriers demonstrated that about 72% of women who inherit a harmful BRCA1 mutation and Once an individual’s risk is determined, this risk is about 69% of women who inherit a harmful BRCA2 managed through a number of methods. First, enhanced mutation will develop breast cancer by the age of 80, screening, such as starting breast cancer screenings at a while the cumulative ovarian cancer risk was 44% for younger age or more frequently is an option. Therefore, BRCA1 and 17% for BRCA2 carriers.5 Apart from breast experts typically recommend that BRCA1 or BRCA2 and ovarian cancers, BRCA1 and BRCA2 mutations have mutation carriers begin clinical breast examinations been associated with fallopian tube and peritoneal starting at age 25 to 35 years old, along with a cancers. Likewise, men with BRCA2 mutations, and to a mammogram every year. If detected at an early stage, lesser extent BRCA1 mutations, are at an increased risk breast cancer may have a better probability of being of breast and prostate cancers, while both men and treated successfully. In contrast, ovarian cancer does not women are at an elevated risk of pancreatic cancer.2 have an established early screening method.2 Table 1: Cancer Risk in General Population Additionally, risk-reducing prophylactic surgery is Compared to BRCA1/2 Carriers available to remove at-risk tissue, such as a bilateral Cancer General BRCA1 BRCA2 prophylactic mastectomy to reduce the risk of breast Population Carrier Carrier cancer development. In regards to reducing ovarian Risk4 Risk4 Risk4 cancer risk, a woman’s ovaries and fallopian tubes can 2 Breast 12% 46-87% 38-84% be removed. Ovarian 1-2% 39-63% 16.5-27% Lastly, chemoprevention medications can be utilized to In order to determine an individual’s BRCA1 and BRCA2 reduce the risk of cancer. For example, tamoxifen or status, multigene (panel) testing is used to conduct next- raloxifene are FDA-approved to reduce the risk of breast generation sequencing to detect harmful mutations. cancer in women at high risk of development. Similarly, However, the expert consensus argues for testing oral contraceptives are thought to reduce the risk of individuals who do not have cancer only when the ovarian cancer by around 50% in both the general population and women with harmful BRCA1 and BRCA2 individual’s personal or family history suggests the 2 probable incidence of a harmful mutation due to the mutations. fairly infrequent incidence of harmful BRCA1 and BRCA2 gene mutations in the general population. In Overall, BRCA1 and BRCA2 mutations stand at the particular, the United States Preventive Services Task forefront of genetic mutations leading to breast and Force recommends that women who have family ovarian cancers. Therefore, knowledge of family history members with breast, ovarian, fallopian tube, or and personal risk are significant factors necessary for peritoneal cancer be evaluated to determine if they have proper risk management. When risk is properly assessed, a family history that is suggestive of an increased risk of risk management can result in early detection and a a harmful mutation in BRCA1 or BRCA2.2 higher probability of successful treatment. References: When an individual’s family history is indicative of BRCA1 or BRCA2 mutations, it is recommended to first 1. National Cancer Institute. The genetics of cancer. NCI at the NIH. 2019. test the family member with cancer if possible. If this 2. National Cancer Institute. BRCA mutations: cancer risk and individual is shown to have a harmful BRCA1 or BRCA2 genetic testing. NCI at the NIH. 2019. mutation, other family members should then consider 3. Mehrgou A, Akouchekian M. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med J genetic counseling to determine potential risks and the Islam Repub Iran. 2016;30:369. need for genetic testing. If genetic testing is performed, a 4. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, positive test indicates that the individual has inherited a Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2016, known harmful mutation in BRCA1 or BRCA2; thus, an National Cancer Institute. Bethesda, MD, increased risk of developing certain cancers is present. https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site, April 2019. However, a positive result does not determine whether 5. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, or not the individual will ultimately develop cancer, as Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 some individuals who inherit these mutations never Mutation Carriers. JAMA. 2017;317(23):2402-2416. 5-HT3 Receptor Dolasetron Antiemesis Treatment Antagonists (5-HT3 RA) Granisetron Ondansetron for Chemotherapy- Palonosetron Corticosteroid Dexamethasone Induced Nausea and Atypical Antipsychotic Olanzapine Typical Antipsychotic, Prochlorperazine Vomiting Phenothiazine Derivative 5-HT4 Receptor Agonist Metoclopramide Authors: *available in fixed combination with palonosetron only Janelle Solbos, PharmD Candidate 2020 Breakthrough Emesis Treatment Anne Marie Bott, PharmD, BCOP, BCPS Breakthrough and anticipatory nausea can present when NCPS, Alaska Native Medical Center the patient is not actively receiving chemotherapy. Prevention of nausea and vomiting is ideal. If emesis Pharmacists in all roles and positions support patients does occur, this can lead to anticipatory nausea and with knowledge and expertise. Here we discuss vomiting in the future and/or discontinuation of 3 medications that are recommended to prevent and/or chemotherapy. If patients experience emesis despite treat emesis in adult cancer patients, according to the optimal therapy, it is recommended to try an agent from National Comprehensive Cancer Network (NCCN)1 and a different class than was used previously and American Society of Clinical Oncology (ASCO) subsequent antiemetic regimens should be adjusted guidelines2. accordingly. Patients with cancer present in all healthcare settings; Cornerstones of acute CINV management, 5-HT3 RAs, therefore, pharmacists knowledgeable of the agents used NK1 RAs, dexamethasone, and olanzapine, are usually to manage different types of chemotherapy-induced utilized first. Dexamethasone and 5-HT3 RAs are nausea and vomiting (CINV) are better able to provide included in most antiemesis regimens so their use in patient care.