CJON Writing Mentorship Article
NCPD Article

PARP Inhibition: Genomics-Informed Care for Patients With Malignancies Driven by BRCA1/BRCA2 Pathogenic Variants

Carissa Hines-Mitchell

Suzanne M. Mahon
genomic science, PARP inhibitor, BRCA1/BRCA2, germline, somatic, biomarkers
CJON 2023, 27(2), 181-189. DOI: 10.1188/23.CJON.181-189

Background: Germline and somatic biomarker testing for BRCA1/2 pathogenic variants can provide important susceptibility, prognostic, and predictive information, guiding recommendations for care.

Objectives: This article reviews BRCA1/2, DNA damage and repair mechanisms, prevention and screening guidelines for patients with germline pathogenic BRCA1/2 variants, indications for poly (ADP-ribose) polymerase (PARP) inhibitor therapy, associated side effects, tumor resistance, and implications for nurses.

Methods: A comprehensive review of the CINAHL®, MEDLINE®, and PubMed® databases was performed using the following search terms: BRCA1/2, PARP inhibitors, and genomic testing.

Findings: PARP inhibitors are indicated for select patients with malignancies associated with BRCA1/2 pathogenic variants. Awareness of PARP inhibitors, their mechanism of action, indications for use, and associated side effects helps oncology nurses guide patients and families in care recommendations, provide detailed patient education, effectively monitor for side effects, and promote adherence to therapy.

Jump to a section

    Earn free contact hours: Click here to connect to the evaluation. Certified nurses can claim no more than 1 total ILNA point for this program. Up to 1 ILNA point may be applied to Care Continuum OR Coordination of Care OR Diagnosis and Staging OR Nursing Practice OR Oncology Nursing Practice OR Treatment. See www.oncc.org for complete details on certification.

    Genomic science has expanded the scope, complexity, and precision of care for patients with cancer. The understanding of specific genetic pathogenic variants, including BRCA1/BRCA2, has led to updated implications for the prevention, screening, detection, and treatment of certain malignancies. These improvements in the individualization of oncology care delivery present challenges and opportunities for nurses to provide comprehensive care not only for patients but also their families, with the goal of improving outcomes and enhancing quality of life.

    The tumor suppressor genes BRCA1/BRCA2 inhibit cell proliferation and tumor development. Pathogenic variants in these genes increase the risk of developing multiple malignancies, have implications for the selection of therapies, and provide some prognostic information. This article reviews the function of BRCA1/BRCA2 genes, relevant DNA repair mechanisms, prevention and screening guidelines for at-risk individuals, indications for poly (ADP-ribose) polymerase (PARP) inhibitor therapy, associated side effects, tumor resistance, and relevant implications for oncology nurses.

    BRCA1/BRCA2 Biomarker Testing

    Biomarker testing for pathogenic variants, such as in the BRCA1/BRCA2 genes, has revolutionized oncology practice (Mahon, 2020). Biomarker testing can provide valuable information about disease susceptibility, prognosis, and treatment efficacy.

    The BRCA1/BRCA2 genes were isolated more than two decades ago, and early research and clinical practice focused on cancer risks associated with germline (inherited) pathogenic variants in these tumor suppressor genes (Petrucelli et al., 2022). A tumor suppressor gene directs the production of a protein, helping to regulate cell division. When the gene is altered, cell division is uncontrolled, ultimately leading to malignancy (Joyce et al., 2022). Therefore, BRCA1/BRCA2 genes are considered susceptibility biomarkers because a pathogenic variant in either gene is associated with an increased risk of developing breast, ovarian, prostate, pancreatic, or malignant melanoma cancer (National Comprehensive Cancer Network, 2023).

    BRCA1/BRCA2 biomarker testing provides prognostic data. Prognostic biomarkers aid in anticipating oncologic outcomes, including disease progression or recurrence (National Library of Medicine, 2016). For example, detection of a BRCA1 pathogenic variant has been correlated with better overall survival in patients with ovarian cancer; however, the effect of a BRCA2 pathogenic variant on overall survival in ovarian cancer is uncertain (Huang, 2018). A pathogenic BRCA1/BRCA2 variant in prostate cancer may be associated with a short interval to castration resistance (Kimura et al., 2022). Likewise, in pancreatic cancer, a BRCA1/BRCA2 pathogenic variant is independently associated with poor survival outcomes (Blair et al., 2018). Prognostic data are relative to germline and somatic BRCA1/BRCA2 pathogenic variants.

    Researchers have specifically determined that the BRCA1/BRCA2 genes identify and correct double-strand errors as part of the homologous recombination (HR) DNA repair pathway (Carré-Simon & Fabre, 2021). Therefore, BRCA1/BRCA2 are predictive biomarkers that provide information about potentially effective treatments. Malignancies associated with a BRCA1/BRCA2 pathogenic variant are typically sensitive to platinum-based chemotherapies and PARP inhibitors, leading to more favorable outcomes when these treatments are used (Imyanitov & Sokolenko, 2021). Understanding of this information can help oncologists select precise, effective therapies when developing treatment plans for patients with malignancies driven by pathogenic variants in BRCA1/BRCA2.

    DNA Damage and Repair

    DNA is a double-stranded molecule that carries genetic material that encodes directions to develop and sustain living organisms. Throughout the life span, DNA damage can occur because of endogenous and exogenous factors (Carré-Simon & Fabre, 2021). DNA damage and repair occur continuously, and in normal conditions, genomic stability is maintained (Dziadkowiec et al., 2016).

    Genetic changes that lead to malignancy can result from errors that occur as cells divide, damage to DNA because of a carcinogenic exposure, or inherited alterations from the parent(s). Some endogenous causes of DNA damage include misstructured cellular bases during DNA replication and free radicals stemming from metabolic processes (Carré-Simon & Fabre, 2021). Exogenous causes of DNA damage are often because of carcinogens, including chemical and radiation exposure.

    Breaks in DNA strands are a form of DNA damage that can lead to tumor development. In a single-strand break (SSB), only one chain of the genetic material is damaged, whereas in a double-strand break (DSB), both chains become injured. SSBs occur frequently and are repaired more easily. DSBs are more complex and more complicated to repair (see Figure 1). If left unrepaired, DNA damage can lead to a variety of conditions, including malignancy (Pooley & Dunning, 2019).

    FIGURE1

    SSB and DSB Repair

    There are several DNA repair pathways in humans, including base excision repair, nucleotide excision repair, SSB repair, HR repair, nonhomologous end joining, and mismatch repair (Cortesi et al., 2021). PARP is a protein that enables the repair of DNA damage in cells. PARP activity is necessary for the repair of SSBs through the base excision repair pathway. By inhibiting PARP activity, SSBs are not repaired and are converted to DSBs (Rose et al., 2020).

    In DNA with a DSB, there are five main repair pathways: nonhomologous end joining, alternative nonhomologous end joining, single-strand annealing, break-induced replication, and HR (Cortesi et al., 2021). The HR repair mechanism is the most precise, leading to optimal cellular structural repair outcomes. This mechanism takes place after DNA replication but before cell division. DSBs are repaired primarily by the HR repair pathway (Toh & Ngeow, 2021).

    HR-deficient cells are unable to repair DSBs in DNA (Zheng et al., 2020). Over time, unrepaired DSBs can lead to the accumulation of genomic changes, such as insertions and deletions, copy number alterations, or structural rearrangements in chromosomes. These changes result in genomic instability, which leads to carcinogenesis and disease progression.

    BRCA1/BRCA2 Germline and Somatic Pathogenic Variants

    Several notable DNA repair genes play an active role in the HR repair pathway (Mateo et al., 2019). The most studied within the landscape of PARP inhibition are BRCA1/BRCA2 (Toh & Ngeow, 2021). Cells with a germline (inherited) or somatic (acquired) pathogenic variant in a BRCA1/BRCA2 gene are HR-deficient and cannot repair a DSB, leading to apoptosis.

    Pathogenic variants in BRCA1/BRCA2 represent the intersection of germline and somatic biomarker testing, which is becoming a standard of care (Mahon, 2020). Germline pathogenic variants are found in the egg or sperm (germline tissues) and are passed to offspring at conception, with the pathogenic copy present in every cell. Somatic pathogenic variants are alterations in DNA that occur after conception, are not present within the germline tissues, and are not passed on to offspring. Discerning whether the pathogenic variant is germline or somatic guides recommendations for care for the patient and potentially other family members (Petrucelli et al., 2022).

    Pathogenic BRCA1/BRCA2 variants can be identified using germline or somatic biomarker testing. Somatic biomarker testing is often recommended to identify potential targeted treatments (Vlessis et al., 2019). It can also provide information about potential germline risk. If a patient meets criteria based on established guidelines or if testing reveals a pathogenic variant in a gene associated with germline risk, the patient can be referred to a genetics professional for counseling and potential germline testing (DeLeonardis et al., 2019) (see Figure 2). Counseling and assessment can include germline testing for the BRCA1/BRCA2 genes and possibly other genes depending on personal and family medical history.

    FIGURE2

    Genetic biomarker testing provides the ability to determine risks associated with an individual’s malignancy and strategies for prevention and early detection. In addition, biomarker testing can offer clinicians clarity about potentially effective treatments, combination treatments, and treatment resistance. For example, the identification of a germline pathogenic variant in the BRCA1/BRCA2 genes can guide surgical decision-making. The detection of a germline or somatic pathogenic variant in the BRCA1/BRCA2 genes also has implications for PARP inhibitor therapy (National Comprehensive Cancer Network, 2023).

    PARP Inhibitor Therapy

    Considering the specific role PARP plays in HR repair, it is a helpful protein to target in the treatment of malignancies because of an HR-deficient BRCA1/BRCA2 pathogenic variant. PARP inhibitors are oral targeted agents that cause SSBs to be converted to DSBs, which then cannot be repaired, ultimately leading to apoptosis of malignant cells (Mehta & Bothra, 2021). PARP inhibitors are selective in primarily affecting malignant cells and avoiding healthy cells.

    As of March 2023, there are four approved PARP inhibitors, all of which are designated for use in the maintenance treatment of various malignancies, including ovarian, breast, fallopian tube, peritoneal, pancreatic, and prostate (National Comprehensive Cancer Network, 2023). The four PARP inhibitors approved for use are niraparib, olaparib, rucaparib, and talazoparib (Rose et al., 2020). PARP inhibitors have shown overall improvement in progression-free survival in patients with malignancies related to BRCA1/BRCA2 pathogenic variants across related cancer types (Kim et al., 2021). Previous studies have reported that progression-free survival was improved by months (ranging from 2 to 42 months) in patients with advanced ovarian, breast, prostate, and pancreatic cancers related to a BRCA1/BRCA2 pathogenic variant who received PARP inhibitors compared with a placebo (Armstrong, 2021; Brown & Reiss, 2021; Sun et al., 2021; Wu et al., 2021). U.S. Food and Drug Administration–approved PARP inhibitors and indications for each of these drugs are listed in Figure 3.

    FIGURE3

    Understanding the physiology of PARP proteins provides insight into potential side effects. There are 18 PARP proteins, all of which are involved in cellular life and death by DNA repair (Dziadkowiec et al., 2016). Olaparib, niraparib, and talazoparib target PARP1 and PARP2, whereas rucaparib targets PARP1, PARP2, and PARP3 (LaFargue et al., 2019). Side effects are fairly consistent among PARP inhibitors, but the degree of severity may differ among each agent depending on the agent’s binding potential to particular PARP proteins. For example, PARP1 plays a large role in metabolic processes, whereas PARP2 regulates red blood cell production, and PARP3 potentiates PARP1 in enzyme action (LaFargue et al., 2019). Side effects and their severity can often represent the proteins that are targeted, particularly when considering that multiple proteins may be inhibited by one agent.

    Long-term use of PARP inhibitors may be impaired by dose-limiting toxicities, which can be defined as side effects that are severe enough to warrant dose reduction or cessation. Hematologic toxicities, such as anemia, thrombocytopenia, and neutropenia, have been observed at varying degrees with each of these approved agents, but most severely in patients taking niraparib (Jiang et al., 2019). Fatigue and gastrointestinal effects, such as nausea, vomiting, diarrhea, and constipation, have been observed consistently and commonly at varying degrees among each of the approved agents. Of note, transient hepatic impairment has been noted specifically with rucaparib in 10%–17% of patients in two clinical trials (Jiang et al., 2019). Rare but serious myelodysplastic syndromes and acute myeloid leukemia have been reported in as many as 2% of patients using PARP inhibitor agents (Jiang et al., 2019).

    Resistance

    Similar to how side effects can affect the sustainability of PARP inhibitor use, development of tumor resistance may also occur, limiting the length of response to PARP inhibitor therapy. Acquiring tumor resistance eventually leads to the ineffectiveness of PARP inhibitor therapy and subsequently disease progression. A variety of mechanisms may cause tumor resistance, including the reconditioning of HR repair activity, secondary pathogenic variants in the BRCA1/BRCA2 genes, and disruption of genes involved in nonhomologous end joining, which can trigger reactivation of HR deficiency, increased processing rates of PARP inhibitors that lead to decreased drug levels, and manipulation of proteins involved in PARP recruitment and DSB eradication (Rose et al., 2020). Combination therapy with a PARP inhibitor and other agents, including alkylating agents, topoisomerase inhibitors, PI3K (phosphatidylinositol 3-kinase) inhibitors, WEE1 kinase inhibitors, radiation therapy, immunotherapy, and DNMT1, may cause PARP inhibitor resistance (Rose et al., 2020). Of note, resistance to PARP inhibitor therapy can be predicted by initial response. If a patient has a vigorous response to PARP inhibitor therapy initially, it is suspected that they will be at higher risk for developing tumor resistance over the course of treatment, inhibiting the potential for prolonged PARP inhibitor use (Rose et al., 2020).

    Implications for Practice

    Genomic science is rapidly changing oncology screening, prevention, and treatment recommendations for patients and sometimes their families. Pathogenic variants in the BRCA1/BRCA2 genes are an emerging example of how the magnitude of care is being changed by genomic science. Being knowledgeable about these changes has multiple implications for nursing care, including patient education and medication administration/monitoring, follow-up recommendations for long-term screening, and notification and coordination of care for other family members. The Oncology Nursing Society (2022) has published a clinical update outlining the importance of increased nursing education about biomarker testing, PARP inhibitors, and oral adherence that can be used as a reference.

    Patient Education

    Providing quality comprehensive patient education has been reported to contribute to improved survival outcomes, medication adherence, patient autonomy, and satisfaction (Kaupp et al., 2019). For oncology nurses, this includes ensuring that patients and families have a basic understanding of how PARP inhibitors work and why adherence is important. Educating patients and families about safe-handling techniques for oral therapies is also necessary for the well-being of patients and family members. Likewise, informing patients and family members about side effects associated with PARP inhibitors promotes early recognition and treatment, contributing to better overall management.

    It is likely that patients and family members have heard of the BRCA1/BRCA2 genes, and they may express concerns about the risk to other family members (Reisel et al., 2021). This is an opportunity for nurses to provide clarification that germline pathogenic variants can be passed to subsequent generations, whereas somatic pathogenic variants cannot be passed to subsequent generations.

    PARP Inhibitor Administration and Monitoring

    PARP inhibitors are oral agents that patients self-administer. Information on safe handling, storage considerations, and associated side effects of medications is readily available in an oral chemotherapy education sheet from the Oncology Nursing Society (n.d.). Patient education includes information on side effects to report promptly. Nurses can regularly monitor and assess side effects and treatment tolerance at follow-up visits, emphasizing the importance of not missing these appointments.

    Nurses can monitor for hematologic toxicities, fatigue, and gastrointestinal side effects, such as nausea, vomiting, diarrhea, and constipation. Awareness of and assessment for rarer yet higher-acuity side effects, such as hepatotoxicity or hematologic malignancy, is also indicated. Symptoms and side effects are monitored for and graded based on laboratory findings and subjective and objective patient assessments at each follow-up visit. The Common Terminology Criteria for Adverse Events (National Cancer Institute Cancer Therapy Evaluation Program, 2017) can be used to appropriately grade symptoms and side effects. Grade 3–4 toxicities may prompt dose interruption, reduction, or discontinuation. Among clinical trials, the highest percentage of patients reporting grade 3–4 toxicities, such as anemia, neutropenia, and thrombocytopenia, were administered niraparib, followed by rucaparib. Grade 3–4 fatigue occurred most often in patients who were administered rucaparib, followed by niraparib (Jiang et al., 2019). Rates of dose interruption, reduction, and discontinuation were proportionally related. Side effects associated with oral targeted therapies can negatively affect the patient’s quality of life, which ultimately could become a barrier to therapy adherence (Jiang et al., 2019).

    Adherence

    Oral cancer therapies can provide convenience to patients while still achieving optimal treatment outcomes, but adherence is a major concern (Johnson, 2015). Nonadherence to oral therapies can arise because of a variety of barriers and may lead to poor outcomes, such as disease progression or resistance. When treatment begins for patients, nurses can emphasize the importance of adhering to medications as prescribed. Barriers to effective oral therapy treatment include side effects, patients’ lack of knowledge about treatment or forgetfulness, medication costs, and complexity of the treatment regimen (Krikorian et al., 2019). As members of interprofessional teams, nurses can mitigate barriers to patient oral therapy adherence; interventions include initial and ongoing risk assessment during appointments, side effect monitoring, and detailed patient education (Tipton, 2015). Using interprofessional support such as social workers or financial counselors for concerns with affordability can be helpful in examining potential assistance programs.

    Germline BRCA1/BRCA2 Risks and Management

    The intersection of germline and somatic biomarker testing has created new challenges for providers who are using this testing for the selection of a targeted therapy (McGrath et al., 2021). If a germline pathogenic variant is detected, there are implications for the patient and potentially other family members because full siblings and biologic offspring have a 50% chance of also carrying the pathogenic variant. These implications include comprehensive education about risks (see Figure 4) and recommendations for management (see Figure 5). Identification and coordination of this care is regularly provided by genetics professionals.

    FIGURE4

    Ideally, germline genetic testing is preceded by comprehensive counseling with a genetics professional, which includes review of the patient’s pathology report, construction of a three-generation pedigree of maternal and paternal history, selection of the best panel of genes to test, and discussion of the potential risks and benefits of germline biomarker testing (Mahon, 2019). Depending on the clinical practice, this may or may not occur. Nursing assessment to determine whether these are being carried out is a component of ongoing oncology care.

    FIGURE5

    If testing is ordered without consultation with a genetics professional, there is an increased possibility of errors and potential liability (Farmer et al., 2019). If a provider orders testing only for BRCA1/BRCA2 to inform decision-making about the utility of a PARP inhibitor and fails to consider the personal and family history, the provider could order a panel of genes insufficient to the identification of a different pathogenic variant in another gene, leading to gaps in care (Conway et al., 2020). Providers must carefully consider whether they have the knowledge to order the best germline biomarker test and the resources to coordinate care for the family. If a provider fails to identify, inform, and coordinate this care, there is potential liability (Marchant et al., 2020).

    Consideration of potential health disparities, such as demographic region, education level, racial and ethnic background, gender, age, access to care, and socioeconomic status, should also be included in the coordination of genetic assessment and care (Underhill et al., 2016). Telemedicine has greatly increased the availability of genetics professionals, potentially removing a significant barrier to care (Kircher et al., 2021). Aligning with a genetics professional can help ensure best practice, provide more comprehensive care, and decrease potential provider liability.

    The psychosocial ramifications of learning that the family has a germline pathogenic variant can be distressing (Dibble & Connor, 2022). This distress trajectory can change over time. Ongoing psychosocial assessment is indicated with a standardized evidence-based assessment tool, and referral to a mental health professional is recommended when assessment indicates that evidence-based intervention is needed (Mahon & Carr, 2021).

    Indications for germline testing may also be identified following somatic biomarker testing. If the patient has a pathogenic variant with germline risk that was identified with somatic biomarker testing, a standard clinical protocol can ensure that the patient and family are referred to a genetics professional. The genetics professional can then determine whether germline testing is needed for BRCA1/BRCA2 and/or other genes (Mahon, 2020). In addition, when a patient’s disease recurs and a previously unidentified somatic BRCA1/BRCA2 pathogenic variant is found, a genetics professional can provide insight as to whether the patient should undergo repeat germline testing, depending on what testing was previously completed. Providing education about the difference between germline and somatic changes, as well as offering psychosocial support, may be helpful because waiting for germline testing results can be an additional stressor for patients coping with a diagnosis of malignancy.

    IMPLICATIONS

    Conclusion

    Genomic science is transforming oncology care delivery and patient outcomes. The understanding of pathogenic variants in the BRCA1/BRCA2 genes, as well as how they affect cancer risk, prognosis, treatment indications and sensitivity, resistance, and future directions, is essential knowledge for oncology nurses. This cognizance ensures that oncology nurses can deliver appropriate patient education, effectively monitor for side effects, assess and promote adherence, and assist in prevention and screening guidance, empowering them to make meaningful impacts.

    The authors gratefully acknowledge Patricia Friend, PhD, APRN-CNS, AOCNS®, AGN-BC, for her thoughtful comments during the preparation of this manuscript.

    About the Authors

    Carissa Hines-Mitchell, MSN, APRN, FNP-C, AOCNP®, is a hematology/oncology nurse practitioner at the Adena Cancer Center in Chillicothe, OH; and Suzanne M. Mahon, DNS, RN, AOCN®, AGN-BC, FAAN, is a professor emerita in the Division of Hematology and Oncology at Saint Louis University in Missouri. The authors take full responsibility for this content. The authors were participants in the Clinical Journal of Oncology Nursing Writing Mentorship Program. The article has been reviewed by independent peer reviewers to ensure that it is objective and free from bias. Hines-Mitchell can be reached at chinesmitchell@adena.org, with copy to CJONEditor@ons.org. (Submitted October 2022. Accepted December 4, 2022.)

    References

    Armstrong, D.K. (2021). Use of PARP inhibitors for ovarian cancer. Journal of the National Comprehensive Cancer Network, 19(5.5), 636–638. https://doi.org/10.6004/jnccn.2021.5013

    AstraZeneca. (2020). Lynparza® (olaparib) [Package insert]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl…

    Blair, A.B., Groot, V.P., Gemenetzis, G., Wei, J., Cameron, J.L., Weiss, M.J., . . . He, J. (2018). BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic ductal adenocarcinoma. Journal of the American College of Surgeons, 226(4), 630–637. https://doi.org/10.1016/j.jamcollsurg.2017.12.021

    Brown, T.J., & Reiss, K.A. (2021). PARP inhibitors in pancreatic cancer. Cancer Journal, 27(6), 465–475. https://doi.org/10.1097/ppo.0000000000000554

    Carré-Simon, À., & Fabre, E. (2021). 3D genome organization: Causes and consequences for DNA damage and repair. Genes, 13(1), 7. https://doi.org/10.3390/genes13010007

    Clovis Oncology. (2020). Rubraca® (rucaparib) [Package insert]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209115s004lbl…

    Conway, M.E., Kalejta, C.D., Sternen, D.L., & Singh, I.R. (2020). The importance of genetics experts in optimizing genetic test orders through prospective and retrospective reviews. American Journal of Clinical Pathology, 153(4), 537–547. https://doi.org/10.1093/ajcp/aqz188

    Cortesi, L., Piombino, C., & Toss, A. (2021). Germline mutations in other homologous recombination repair-related genes than BRCA1/2: Predictive or prognostic factors? Journal of Personalized Medicine, 11(4), 245. https://doi.org/10.3390/jpm11040245

    DeLeonardis, K., Hogan, L., Cannistra, S.A., Rangachari, D., & Tung, N. (2019). When should tumor genomic profiling prompt consideration of germline testing? Journal of Oncology Practice, 15(9), 465–473. https://doi.org/10.1200/jop.19.00201

    Dibble, K.E., & Connor, A.E. (2022). Anxiety and depression among racial/ethnic minorities and impoverished women testing positive for BRCA1/2 mutations in the United States. Supportive Care in Cancer, 30(7), 5769–5778. https://doi.org/10.1007/s00520-022-07004-7

    Dziadkowiec, K.N., Gąsiorowska, E., Nowak-Markwitz, E., & Jankowska, A. (2016). PARP inhibitors: Review of mechanisms of action and BRCA1/2 mutation targeting. Menopause Review, 15(4), 215–219. https://doi.org/10.5114/pm.2016.65667

    Farmer, M.B., Bonadies, D.C, Mahon, S.M., Baker, M.J., Ghate, S.M., Munro, C., . . . Matloff, E.T. (2019). Adverse events in genetic testing: The fourth case series. Cancer Journal, 25(4), 231–236. https://doi.org/10.1097/ppo.0000000000000391

    GlaxoSmithKline. (2020). Zejula (niraparib) [Package insert]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s01…

    Huang, Y.-W. (2018). Association of BRCA1/2 mutations with ovarian cancer prognosis: An updated meta-analysis. Medicine, 97(2), e9380. https://doi.org/10.1097/md.0000000000009380

    Imyanitov, E., & Sokolenko, A. (2021). Mechanisms of acquired resistance of BRCA1/2-driven tumors to platinum compounds and PARP inhibitors. World Journal of Clinical Oncology, 12(7), 544–556. https://doi.org/10.5306/wjco.v12.i7.544

    Jiang, X., Li, W., Li, X., Bai, H., & Zhang, Z. (2019). Current status and future prospects of PARP inhibitor clinical trials in ovarian cancer. Cancer Management and Research, 11, 4371–4390. https://doi.org/10.2147/cmar.s200524

    Johnson, L.A. (2015). Factors influencing oral adherence: Qualitative metasummary and triangulation with quantitative evidence. Clinical Journal of Oncology Nursing, 19(3, Suppl.), 6–30. https://doi.org/10.1188/15.s1.CJON.6-30

    Joyce, C., Rayi, A., & Kasi, A. (2022). Tumor suppressor genes. StatPearls. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK532243

    Kaupp, K., Scott, S., Minard, L.V., & Lambourne, T. (2019). Optimizing patient education of oncology medications: A quantitative analysis of the patient perspective. Journal of Oncology Pharmacy Practice, 25(6), 1445–1455. https://doi.org/10.1177/1078155219843675

    Kim, D.-S., Camacho, C.V., & Kraus, W.L. (2021). Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance. Experimental and Molecular Medicine, 53(1), 42–51. https://doi.org/10.1038/s12276-021-00557-3

    Kimura, H., Mizuno, K., Shiota, M., Narita, S., Terada, N., Fujimoto, N., . . . Akamatsu, S. (2022). Prognostic significance of pathogenic variants in BRCA1, BRCA2, ATM and PALB2 genes in men undergoing hormonal therapy for advanced prostate cancer. British Journal of Cancer, 127(9), 1680–1690. https://doi.org/10.1038/s41416-022-01915-2

    Kircher, S., Braccio, N., Gallagher, K., Carlos, R., Wagner, L., Smith, M.L., . . . Benson, A.B. (2021). Meeting patients where they are: Policy platform for telehealth and cancer care delivery. Journal of the National Comprehensive Cancer Network, 19(12), 1470–1474. https://doi.org/10.6004/jnccn.2021.7111

    Krikorian, S., Pories, S., Tataronis, G., Caughey, T., Chervinsky, K., Lotz, M., . . . Weissmann, L. (2019). Adherence to oral chemotherapy: Challenges and opportunities. Journal of Oncology Pharmacy Practice, 25(7), 1590–1598. https://doi.org/10.1177/1078155218800384

    LaFargue, C.J., Dal Molin, G.Z., Sood, A.K., & Coleman, R.L. (2019). Exploring and comparing adverse events between PARP inhibitors. Lancet Oncology, 20(1). e15–e28. https://doi.org/10.1016/s1470-2045(18)30786-1

    Mahon, S.M. (2019). Coordination of genetic care: More important and complicated than it seems. Journal of the National Comprehensive Cancer Network, 17(11), 1272–1276. https://doi.org/10.6004/jnccn.2019.7343

    Mahon, S.M. (2020). Tumor genomic testing: Identifying characteristics associated with germline risk for developing malignancy. Clinical Journal of Oncology Nursing, 24(6), 623–626. https://doi.org/10.1188/20.CJON.623-626

    Mahon, S.M., & Carr, E. (2021). Distress: Common side effect. Clinical Journal of Oncology Nursing, 25(6, Suppl.), 24. https://doi.org/10.1188/21.CJON.s2.24

    Marchant, G., Barnes, M., Evans, J.P., LeRoy, B., & Wolf, S.M. (2020). From genetics to genomics: Facing the liability implications in clinical care. Journal of Law, Medicine and Ethics, 48(1), 11–43. https://doi.org/10.1177/1073110520916994

    Mateo, J., Lord, C.J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., . . . de Bono, J.S. (2019). A decade of clinical development of PARP inhibitors in perspective. Annals of Oncology, 30(9), 1437–1447. https://doi.org/10.1093/annonc/mdz192

    McGrath, S.P., Peabody, A.E., Jr., Walton, D., & Walton, N. (2021). Legal challenges in precision medicine: What duties arising from genetic and genomic testing does a physician owe to patients? Frontiers in Medicine, 8, 663014. https://doi.org/10.3389/fmed.2021.663014

    Mehta, P., & Bothra, S.J. (2021). PARP inhibitors in hereditary breast and ovarian cancer and other cancers: A review. Advances in Genetics, 108, 35–80. https://doi.org/10.1016/bs.adgen.2021.08.002

    National Cancer Institute Cancer Therapy Evaluation Program. (2017). Common Terminology Criteria for Adverse Events [v.5.0]. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/doc…

    National Comprehensive Cancer Network. (2023). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Genetic/familial high-risk assessment: Breast, ovarian, and pancreatic version [v.2.2023]. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

    National Library of Medicine. (2016). BEST (biomarkers, endpoints, and other tools) resource. National Institutes of Health. https://www.ncbi.nlm.nih.gov/books/NBK338448/#IX-S

    Oncology Nursing Society. (n.d.). Oral chemotherapy education sheets. https://www.ons.org/clinical-practice-resources/oral-chemotherapy-educa…

    Oncology Nursing Society. (2022). Clinical update: PARP inhibitors. https://www.ons.org/clinical-practice-resources/clinical-update-parp-in…

    Petrucelli, N., Daly, M.B., & Pal, T. (2022). BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. In M.P. Adam, H.H. Ardinger, R.A. Pagon, & S.E. Wallace (Eds.), GeneReviews®. Retrieved February 28, 2023, from https://www.ncbi.nlm.nih.gov/books/NBK1247

    Pfizer. (2018). TalzennaTM (talazoparib) [Package insert]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211651s000lbl…

    Pooley, K.A., & Dunning, A.M. (2019). DNA damage and hormone-related cancer: A repair pathway view. Human Molecular Genetics, 28(R2), R180–R186. https://doi.org/10.1093/hmg/ddz206

    Reisel, D., Baran, C., & Manchanda, R. (2021). Preventive population genomics: The model of BRCA related cancers. Advances in Genetics, 108, 1–33. https://doi.org/10.1016/bs.adgen.2021.08.001

    Rose, M., Burgess, J.T., O’Byrne, K., Richard, D.J., & Bolderson, E. (2020). PARP inhibitors: Clinical relevance, mechanisms of action and tumor resistance. Frontiers in Cell and Developmental Biology, 8, 564601. https://doi.org/10.3389/fcell.2020.564601

    Sun, X., Wang, X., Zhang, J., Zhao, Z., Feng, X., Liu, L., & Ma, Z. (2021). Efficacy and safety of PARP inhibitors in patients with BRCA-mutated advanced breast cancer: A meta-analysis and systematic review. Breast, 60, 26–34. https://doi.org/10.1016/j.breast.2021.08.009

    Tipton, J.M. (2015). Overview of the challenges related to oral agents for cancer and their impact on adherence. Clinical Journal of Oncology Nursing, 19(3, Suppl.), 37–40. https://doi.org/10.1188/15.s1.CJON.37-40

    Toh, M., & Ngeow, J. (2021). Homologous recombination deficiency: Cancer predispositions and treatment implications. Oncologist, 26(9), e1526–e1537. https://doi.org/10.1002/onco.13829

    Underhill, M.L., Jones, T., & Habin, K. (2016). Disparities in cancer genetic risk assessment and testing. Oncology Nursing Forum, 43(4), 519–523. https://doi.org/10.1188/16.ONF.519-523

    Vlessis, K., Purington, N., Chun, N., Haraldsdottir, S., & Ford, J.M. (2019). Germline testing for patients with BRCA1/2 mutations on somatic tumor testing. JNCI Cancer Spectrum, 4(1), pkz095. https://doi.org/10.1093/jncics/pkz095

    Wu, K., Liang, J., Shao, Y., Xiong, S., Feng, S., & Li, X. (2021). Evaluation of the efficacy of PARP inhibitors in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. Frontiers in Pharmacology, 12, 777663. https://doi.org/10.3389/fphar.2021.777663

    Zheng, F., Zhang, Y., Chen, S., Weng, X., Rao, Y., & Fang, H. (2020). Mechanism and current progress of poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomedicine and Pharmacotherapy, 123, 109661. https://doi.org/10.1016/j.biopha.2019.109661