Geentics Cancer Paper This Weekend With Lesser Slides Review

INTRODUCTION

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Although the contribution of heredity to prostate cancer has long been known, the underlying genetic causes remained elusive. Recent discoveries reveal that a significant fraction of men with metastatic prostate cancer (mPC) comport germline mutations in Deoxyribonucleic acid damage repair (DDR) genes, including BRCA1, BRCA2, and ATM.^ane,two Compelling early findings suggest that germline and/or somatic alterations in these and other DDR genes may predict response to poly (ADP-ribose) polymerase (PARP) inhibitors and platinum chemotherapy.^3-5 Germline mutations in mismatch repair (MMR) genes (MSH2, MSH6, MLH1, and PMS2), which are associated with Lynch syndrome and development of tumors with defective Deoxyribonucleic acid MMR or high microsatellite instability (MSI), may identify candidates for immunotherapy with programmed prison cell death protein 1 checkpoint inhibitors.⁶ In addition, response to other systemic therapies for prostate cancer may be influenced past the presence of a germline and/or somatic DDR gene mutation.^7-10

The current models for genetic counseling and testing were developed for cess of individuals and families with suspicion for hereditary cancer syndromes and focused on take a chance cess, cancer screening, and risk reduction (eg, salpingo-oophorectomy for female BRCA1/2 carriers). For prostate cancer, genetic counseling and testing practices are newly driven by a growing interest in identifying patients who are candidates for enrollment in biomarker-selected clinical trials. This treatment-driven observation, where patients are referred for germline testing in part for therapy pick, presents unique opportunities and challenges for practitioners regarding appropriate commitment of elements of genetic counseling in a feasible manner.

The Prostate Cancer Clinical Trials Consortium is a group of researchers from eleven institutions working together to develop novel therapeutics and biomarkers, translating scientific discoveries to improve standards of care in prostate cancer. The Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium was established in June of 2017 in response to the growing intersection betwixt germline genetics and therapeutics. In this commodity, we outline the special considerations when genetic testing is used for therapeutic purposes in men with mPC and to suggest areas of future research. Although germline genetics may affect direction decisions in early-phase prostate cancer, we focus hither on advanced affliction because of the current therapeutic and clinical trial implications, although many of the principles outlined employ to all stages of affliction.

GERMLINE DNA REPAIR MUTATIONS IN RECURRENT AND METASTATIC PROSTATE CANCER

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Prostate cancer has a significant heritable component, with 57% of the take chances attributed to genetic factors.^11,12 Mutations in loftier and moderately penetrant genes involved in DDR can be associated with varying degrees of increased predisposition to prostate cancer (Appendix Table A1). In a landmark study, the incidence of inherited pathogenic DDR mutations in men with mPC was 11.viii% (v.iii% with mutations in BRCA2, 1.ix% in CHEK2, and one.five% in ATM).¹ This prevalence was significantly college compared with men with localized prostate cancer (xi.8% v 4.6%; P < .001). In a second confirmatory study, the prevalence of germline pathogenic DDR mutations in unselected patients with recurrent or mPC was 14.0% (6.0% in BRCA2, ii.0% in CHEK2, and ii.0% in ATM), with an apparent enrichment in men with intraductal or ductal histologic features.¹³ An clan betwixt germline BRCA2 mutations and intraductal prostate cancer was also reported in a prior study.¹⁴

Germline BRCA1/2 mutation carriers may have more aggressive affliction at presentation and take a higher risk of recurrence and prostate cancer–specific bloodshed compared with noncarriers.^15-17 In a retrospective case-case study of patients with low-chance localized prostate cancer and patients who died as a result of disease, the combined carrier rate of BRCA1, BRCA2, and ATM mutations was higher in lethal cases (6.1% v 1.4%; P < .001), and those with mutations had a shorter interval to expiry afterwards diagnosis.¹⁸

Men with Lynch syndrome (due to germline mutations in MLH1, MSH2, MSH6, or PMS2) may also be at increased run a risk of prostate cancer; notwithstanding, information are conflicting, with some studies showing a two- to 5-fold increased gamble and others showing no increased adventure.^xix-23 These adventure ranges may be due to the different penetrance of Lynch genes; there is suggestion that prostate cancer risk is particularly elevated in MSH2 carriers.^24,25 Information technology is likewise likely that equally screening for colorectal cancer improves, men with Lynch syndrome are living longer, and thus the incidence of older-onset cancers is increasing.²⁵ Unfortunately, many patients with prostate cancer with germline MMR mutations do not meet traditional family history criteria.²⁶ In men with Lynch syndrome, prostate cancer infrequently represents the index cancer; all the same, prostate tumors tin lack MMR cistron protein expression or show MSI.^21,27 In a study of 451 patients with prostate cancer, 3% of patients had tumors with somatic alterations in MMR genes, which predicted for high mutation count.²⁸ Identifying patients with mPC whose tumors harbor these features has become increasingly relevant, considering the programmed cell expiry poly peptide 1 immune checkpoint inhibitor pembrolizumab was approved by the US Food and Drug Administration for handling of any cancer with scarce MMR or loftier MSI.²⁹

CLINICAL TRIALS USING GERMLINE MUTATIONS AS ELIGIBILITY CRITERIA

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An increasing number of therapeutic clinical trials in prostate cancer are using presence of DDR mutations, including germline, every bit an eligibility requirement for enrollment, similar to advanced ovarian and breast cancers with germline BRCA1/2 mutations (eg, olaparib, rucaparib; Table ane). For example, the BRCAaway trial (ClinicalTrials.gov identifier: NCT03012321) is a phase II randomized trial of the PARP inhibitor olaparib versus abiraterone versus the combination of the two agents in men with germline or somatic homologous recombination deficiency mutations. Additional trials are exploring the efficacy of rucaparib, niraparib, and olaparib as unmarried agent for men with metastatic castration-resistant prostate cancer and a deleterious genomic alteration, either germline or somatic, in BRCA2, BRCA1, and other DDR genes (ClinicalTrials.gov identifiers: NCT02952534, NCT02975934, NCT02854436, NCT02987543). The TRIUMPH (Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations) trial (ClinicalTrials.gov identifier: NCT03413995) will enroll men with metastatic hormone-sensitive prostate cancer and a germline DDR factor pathogenic amending, who will exist treated with the PARP inhibitor rucaparib in the absence of hormonal therapy. Information technology is anticipated that an increasing number of men with mPC volition undergo genetic testing and that new trials will exist designed and implemented for the germline DDR-scarce population.

Table 1. Selected Therapeutic Clinical Trials in Prostate Cancer With Relevance to Germline Genetics

CONTEXTUAL DIFFERENCES AND IMPORTANCE OF CONFIRMING PATIENT PRIORITIES

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Adjacent-generation sequencing has made germline testing more accessible and comprehensive, and broader cohorts of patients with cancer are beingness tested using large gene panels. These approaches have the potential to address ii of import but distinct objectives: first, treatment and clinical trial possibilities, and, second, inherited cancer risk. For providers, it is worth discussing and confirming patient goals before offer testing—for example, request whether patients are interested primarily in handling options, familial risk assessment, or both. Effigy 1 provides a framework for genetic testing inside the context of treatment decisions. Oncologist-driven genetic teaching is ideally in close collaboration with a cancer genetics service. Family history intake is critical and needs to be streamlined for oncology and clinical trial settings. Table 2 summarizes clinical criteria to consider for referral to genetic counseling.

Fig 1. Framework for approaching genetic testing within the context of therapeutic decisions. (*) Currently primarily relevant to metastatic and high-risk localized prostate cancer, but likely volition include earlier disease states in the future. GC, genetic counseling.

Table two. Referral Criteria for Genetic Counseling for Men with Prostate Cancer

This panel agrees that men with prostate cancer who undergo germline genetic testing for therapeutic or clinical trial options should receive pretest education on the implications of a positive outcome for themselves and for their families. Which genes should be included in testing may vary if the setting is treatment decision making versus take a chance assessment and chance management. For example, although at least BRCA1/2 and MMR genes should be tested for men who meet criteria for the corresponding syndromes, boosted genes, such as ATM, CHEK2, and PALB2, could be included for therapeutic decision making, peculiarly in the clinical trial setting.^4,xxx,31

TUMOR-ONLY SEQUENCING MAY Identify GERMLINE MUTATIONS

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Targeted side by side-generation sequencing of the tumor is likewise increasingly being used for treatment conclusion making and clinical trial eligibility determination. Although the goal of testing may be to identify handling options, there is a possibility that somatic testing may identify germline mutations that are reflected in tumor sequence. In several recent studies of enquiry somatic sequencing, germline mutations with clinical implications were identified.^32,33 Tumor sequencing may even exist more sensitive in detecting genetic syndromes, such as Lynch, than the traditional molecular tests.³⁴

Well-nigh commercial tumor assays practise not specifically report whether a mutation is present in the germline, and some subtract the germline component, but the presence of well-described founder mutations may be highly suggestive. For instance, the Ashkenazi Jewish BRCA1/2 founder mutations (BRCA1 185delAG; BRCA1 5382insC; BRCA2 6174delT) are almost always germline, not somatic, events, and ordering providers should exist familiar with them. Somatic tumor profiling tin can also identify increased mutation load and MSI, which tin can be associated with germline MMR mutations (Lynch syndrome).³⁵

Although information technology seems that most patients are interested in knowing secondary germline findings, they also expect their providers to offer controlling guidance and clarify central information.^36,37 This panel agrees that men with prostate cancer who undergo tumor-based genetic testing for therapeutic or clinical trial options should exist educated about the potential for uncovering germline mutations, which may warrant referral to a cancer genetic specialist for confirmatory germline testing. This console recommends that if a BRCA1 or BRCA2 mutation is identified on tumor-based testing, patients should be referred for discussion of dedicated, confirmatory germline testing. Moreover, if increased mutational load, a loftier MSI, or MMR deficiency is identified in tumor-merely profiling, the patient's family history and personal history of other malignancies should be confirmed and reviewed with consideration for referral for dedicated confirmatory germline testing.

Need FOR NEW GENETICS Care Delivery MODELS

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A major challenge is how best to integrate the workflow and provide the clinical back up needed for responsible genetics care. The traditional clinical genetics cancer care delivery model—where patients are referred to a genetic counselor for in-person, pretest run a risk assessment and education and in-person post-exam counseling—cannot meet the projected demand for testing of patients with prostate cancer, some facing time-sensitive treatment decisions. Even when testing is performed primarily for treatment choice, edifice in systems for those who are interested in testing of family members is of disquisitional importance.

Current barriers to genetic testing have been described in the context of testing for cancer predisposition in hereditary breast and ovarian cancer and Lynch syndromes. These barriers include process issues (referral to genetic counseling and testing, admission, wait times, insurance coverage); physician knowledge, comfort, and time; patients' lack of awareness and understanding; and refusal of testing. With appropriate education, patients may be more than interested in pursuing testing. For example, > 85% of patients with ovarian cancer reported willingness to exist tested if there were therapeutic implications or benefit to family, and a bulk believed that genetic testing should be offered earlier or at the fourth dimension of diagnosis.³⁸

When testing for therapeutic decision making, the power to undergo cess and testing and receive results in a timely manner is of utmost importance. Newer approaches in cancer risk genetics include video- or phone-based pretest counseling and mainstreaming, an approach in which trained individuals provide standardized consenting and counseling before testing and genetics referral.³⁹ The ENGAGE (Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer) study of oncologist-led BRCA1/2 mutation testing in women with ovarian cancer showed that this process is feasible, with high patient satisfaction.⁴⁰ These alternate genetic counseling commitment approaches demand to be studied for provider feasibility and patient acceptability. Several trials at our sites are seeking to explore some of these new commitment models (Table iii).

Table 3. Clinical Trials Testing Novel Approaches to Genetic Testing

SPECIAL CHALLENGES IN UNDERSERVED POPULATIONS

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Intensive efforts are needed to ensure that genetic assessment is available to underserved populations, which include ethnic and racial minorities, people of depression income, and those in rural areas, among others.^41,42 Although rates of germline testing have not been studied in different ethnic and racial subgroups of men with prostate cancer, bear witness shows that black and Hispanic women with breast cancer are essentially less likely to undergo genetic testing.^43,44 Reasons for disparities in genetic testing may include differences in dr. referrals, distrust and/or lack of understanding of genetics and cancer risk, fear of genetic bigotry on the part of insurers, and disproportionate financial and time burdens for patients with limited resources.^44-50 Ensuring equitable access to genetic testing for black men with prostate cancer may be peculiarly important, because some preliminary studies show they may be more probable to have germline mutations in BRCA1 and BRCA2 than white men.⁵¹ This is compounded by the fact that black men have a 2.4 times greater adventure of expiry from prostate cancer, are more likely to present with tardily-stage affliction, and are significantly less probable to receive definitive handling than non-Hispanic white men.^52-55

Improving access to genetic testing in geographically remote areas, where availability of genetic counselors is scare, is too an active area of inquiry. Telephone genetic consults, and other novel genetic cess, education, and testing delivery methods, show promise.⁵⁶ To expand our knowledge and evidence of about effective testing strategies, men with prostate cancer should be offered genetic testing in the setting of clinical trials whenever viable.

THE CRUCIAL Responsibleness OF CASCADE TESTING

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Cascade testing is the systematic identification of individuals at risk for a hereditary status through extension of genetic testing to biologic relatives. Although awareness of cascade testing is important in whatsoever situation where a germline mutation is identified, it can be especially of import when genetic testing is performed for therapeutic selection. In contrast to patients who pursue genetic testing because of familial cancer hazard, those who undergo germline testing for therapy selection may be less aware of the potential implications to family members, because they were not necessarily tested considering of an identified familial take a chance. Moreover, men with prostate cancer are frequently diagnosed when their children are adults, can pursue testing, and, if positive, undergo enhanced cancer screening or risk-reduction strategies.

There are several known barriers for a patient's communication of results to family members. In BRCA1/2 screening studies, factors associated with of lack of communication include high worry almost genetic risks, low interest or agreement of genomic data, and negative family history.^57-59 Men and second-caste relatives are less likely to pursue genetic testing.⁵⁸ Thus, in that location is an opportunity through pedagogy to increase familial communication of results. This console agrees that when germline testing is performed, the ordering provider should be knowledgeable and work with local cancer genetics experts to offer cascade testing for family members.

CONCLUSION AND Futurity RESEARCH DIRECTIONS

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Recent exciting discoveries in prostate cancer genetics and potential therapeutic interventions with PARP inhibitors and platinum chemotherapies take led to a rapid increase in germline testing for men with mPC. The traditional framework for genetic testing was developed for individuals believed to exist at risk for inherited syndromes, but this model requires adaptation for men with mPC who are increasingly referred for genetic testing to aid in treatment decisions. In this article, we accept highlighted special considerations with this treatment-driven ascertainment approach and described areas of enquiry needs (Tables 4 and 5). As the field apace evolves, close collaboration between oncologists, urologists, clinical geneticists and counselors, researchers, and indeed, patients themselves, among others, will ensure that we develop the best practices to do good patients with mPC and their families.

Table 4. Challenges and New Enquiry Directions

Table 5. Consensus Statements

© 2018 by American Society of Clinical Oncology

Supported by the Office of the Banana Secretarial assistant of Defense for Health Affairs, through the Prostate Cancer Research Program nether Awards No. W81XWH-17-2-0043, W81XWH-17-ii-0018, W81XWH-17-2-0017, W81XWH-17-2-0020, W81XWH-17-two-002, W81XWH-17-two-00221, W81XWH-17-2-0027, and W81XWH-15-ii-0018, the Prostate Cancer Foundation (G.I.C., E.Due south.A., W.A., H.H.C.), the Found for Prostate Cancer Research, the Pacific Northwest Prostate Cancer National Institutes of Health SPORE Grant No. CA097186, and National Cancer Establish Center Cadre Grant No. P30 CA008748.

Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

Conception and design: Channing J. Paller, Wassim Abida, Joshi J. Alumkal, Daniel J. George, Celestia S. Higano, Akash Patnaik, Charles J. Ryan, Edward Chiliad. Schaeffer, Mary-Ellen Taplin, Noah D. Kauff, Jacob Vinson, Emmanuel Southward. Antonarakis, Heather H. Cheng

Collection and associates of data: Maria I. Carlo, Veda N. Giri, Channing J. Paller, Tomasz M. Beer, Elisabeth I. Heath, Rana R. McKay, Mary-Ellen Taplin, Noah D. Kauff, Jacob Vinson, Emmanuel Due south. Antonarakis, Heather H. Cheng

Data analysis and estimation: Maria I. Carlo, Veda N. Giri, Channing J. Paller, Joshi J. Alumkal, Tomasz M. Beer, Himisha Beltran, Daniel J. George, Elisabeth I. Heath, Rana R. McKay, Alicia K. Morgans, Akash Patnaik, Charles J. Ryan, Walter Thousand. Stadler, Mary-Ellen Taplin, Noah D. Kauff, Jacob Vinson, Emmanuel S. Antonarakis

Manuscript writing: All authors

Last approval of manuscript: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The post-obit represents disclosure information provided past authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family unit Member, Inst = My Establishment. Relationships may not chronicle to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, delight refer to www.asco.org/rwc or ascopubs.org/po/writer-centre.

Maria I. Carlo

No human relationship to disclose

Veda Northward. Giri

No human relationship to disclose

Channing J. Paller

Consulting or Informational Office: Dendreon

Research Funding: Eli Lilly (Inst)

Wassim Abida

Honoraria: CARET

Consulting or Advisory Role: Clovis Oncology

Inquiry Funding: AstraZeneca, Zenith Epigenetics, Clovis Oncology, GlaxoSmithKline (Inst)

Travel, Accommodations, Expenses: GlaxoSmithKline

Joshi J. Alumkal

Consulting or Informational Role: Astellas Pharma, Bayer AG, Janssen Biotech

Research Funding: Aragon Pharmaceuticals (Inst), Astellas Pharma (Inst), Novartis (Inst), Zenith Epigenetics (Inst), Gilead Sciences (Inst)

Tomasz M. Beer

Stock and Other Ownership Interests: Salarius Pharmaceuticals

Consulting or Advisory Role: AbbVie, AstraZeneca, Astellas Pharma, Bayer AG, Boehringer Ingelheim, Clovis Oncology, Janssen Biotech, Janssen Oncology, Janssen Inquiry & Development, Johnson & Johnson, Janssen Nihon, Merck, Pfizer

Research Funding: Boehringer Ingelheim (Inst), Bristol-Myers Squibb/Medarex (Inst), Janssen Inquiry & Evolution (Inst), Medivation/Astellas (Inst), Oncogenex (Inst), Sotio (Inst), Sotio, Theraclone Sciences (Inst)

Himisha Beltran

Consulting or Advisory Role: Janssen Oncology, Genzyme, GlaxoSmithKline, AbbVie

Research Funding: Astellas Pharma (Inst), Janssen (Inst), AbbVie/Stemcentrx, Eli Lilly (Inst), Millennium Pharmaceuticals (Inst)

Daniel J. George

Honoraria: Sanofi, Bayer, Exelixis

Consulting or Advisory Role: Bayer AG, Exelixis, Pfizer, Sanofi, Astellas Pharma, Innocrin Pharmaceuticals, Bristol-Myers Squibb, Genentech, Janssen, Merck Sharp & Dohme, Myovant Sciences

Speakers' Bureau: Sanofi, Bayer, Exelixis

Research Funding: Exelixis (Inst), Genentech (Inst), Janssen Oncology (Inst), Novartis (Inst), Pfizer (Inst), Astellas Pharma (Inst), Bristol-Myers Squibb (Inst), Millennium Pharmaceuticals (Inst), Acerta Pharma (Inst), Bayer (Inst), Dendreon (Inst), Innocrin Pharmaceuticals (Inst)

Expert Testimony: Novartis

Travel, Accommodations, Expenses: Bayer AG, Exelixis, Genentech, Medivation, Merck, Pfizer

Elisabeth I. Heath

Honoraria: Bayer, Dendreon, Sanofi

Consulting or Advisory Role: Agensys

Speakers' Bureau: Sanofi

Inquiry Funding: Tokai Pharmaceuticals (Inst), Seattle Genetics (Inst), Agensys (Inst), Dendreon (Inst), Genentech (Inst), Millennium Pharmaceuticals (Inst), Celldex Therapeutics (Inst), Inovio Pharmaceuticals (Inst), Celgene (Inst)

Celestia S. Higano

Employment: CTI BioPharma (I)

Leadership: CTI BioPharma (I)

Stock and Other Ownership Interests: CTI BioPharma (I)

Honoraria: Genentech

Consulting or Advisory Role: Bayer AG, Ferring Pharmaceuticals, Orion, Astellas Pharma, Clovis Oncology, Asana Biosciences, Endocyte, Blue Earth Diagnostics, Myriad Genetics, Tolmar, Janssen

Research Funding: Aragon Pharmaceuticals (Inst), AstraZeneca (Inst), Dendreon (Inst), Genentech (Inst), Medivation (Inst), Emergent BioSolutions (Inst), Bayer (Inst), Pfizer (Inst), Roche (Inst), Astellas Pharma (Inst)

Travel, Accommodations, Expenses: Bayer AG, Astellas Pharma, Clovis Oncology, Blue World Diagnostics, Endocyte, Ferring Pharmaceuticals, Genentech, Orion Pharma, Menarini, Myriad Genetics, Pfizer

Rana R. McKay

Consulting or Informational Function: Janssen, Novartis

Research Funding: Pfizer (Inst), Bayer AG (Inst)

Alicia Thousand. Morgans

Honoraria: Genentech, Janssen, Johnson & Johnson, Sanofi, AstraZeneca

Consulting or Informational Function: Genentech, AstraZeneca, Sanofi

Akash Patnaik

Honoraria: Clovis Oncology, Merck, Prime number Oncology

Consulting or Advisory Office: Janssen Oncology

Research Funding: Bristol-Myers Squibb (Inst), Progenics Pharmaceuticals (Inst), Janssen Oncology (Inst), Clovis Oncology (Inst)

Travel, Accommodations, Expenses: Clovis Oncology, Bristol-Myers Squibb, Merck, Prime number Oncology, Janssen Oncology

Charles J. Ryan

Honoraria: Janssen Oncology, Astellas Pharma, Bayer

Consulting or Advisory Role: Bayer AG, Millennium Pharmaceuticals, Ferring Pharmaceuticals

Inquiry Funding: Bind Biosciences, Karyopharm Therapeutics, Novartis

Edward Chiliad. Schaeffer

Consulting or Informational Role: OPKO Diagnostics, AbbVie

Walter Chiliad. Stadler

Honoraria: CVS Caremark, Sotio, AstraZeneca, Bristol-Myers Squibb

Consulting or Advisory Function: CVS Caremark, Sotio, AstraZeneca, Bristol-Myers Squibb, Eisai, Bayer AG, Pfizer, Clovis Oncology, Genentech

Research Funding: Bayer AG (Inst), Bristol-Myers Squibb (Inst), Boehringer Ingelheim (Inst), Exelixis (Inst), Novartis (Inst), Genentech (Inst), GlaxoSmithKline (Inst), Medivation (Inst), Pfizer (Inst), Merck (Inst), Millennium Pharmaceuticals (Inst), Janssen (Inst), Johnson & Johnson (Inst), AstraZeneca (Inst), AbbVie (Inst), X4 Pharmaceuticals (Inst), Calithera Biosciences (Inst)

Other Relationship: UpToDate, American Cancer Society

Mary-Ellen Taplin

Honoraria: Janssen-Ortho, Clovis Oncology, Astellas Pharma, Incyte, UpToDate, Research to Practice

Consulting or Advisory Role: Janssen-Ortho, Bayer AG, Guidepoint Global, All-time Doctors, UpToDate, Clovis Oncology, Research to Practice, Myovant Sciences, Incyte

Research Funding: Janssen-Ortho (Inst), Medivation (Inst), Bayer (Inst), Tokai Pharmaceuticals (Inst)

Travel, Accommodations, Expenses: Medivation, Janssen Oncology, Tokai Pharmaceuticals, Astellas Pharma, Incyte

Noah D. Kauff

No human relationship to disembalm

Jacob Vinson

No relationship to disclose

Emmanuel South. Antonarakis

Honoraria: Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA Pharma, Astellas Pharma, Merck, AstraZeneca, Clovis Oncology

Consulting or Informational Part: Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA Pharma, Astellas Pharma, Merck, AstraZeneca, Clovis Oncology

Research Funding: Janssen Biotech (Inst), Johnson & Johnson (Inst), Sanofi (Inst), Dendreon (Inst), Aragon Pharmaceuticals (Inst), Exelixis (Inst), Millennium Pharmaceuticals (Inst), Genentech (Inst), Novartis (Inst), Astellas Pharma (Inst), Tokai Pharmaceuticals (Inst), Merck (Inst), AstraZeneca (Inst), Clovis Oncology (Inst), Constellation Pharmaceuticals (Inst)

Patents, Royalties, Other Intellectual Property: Co-inventor of a biomarker engineering that has been licensed to Qiagen

Travel, Accommodations, Expenses: Sanofi, Dendreon, Medivation

Heather H. Cheng

Research Funding: Inovio Pharmaceuticals, Sanofi, Astellas Medivation, Janssen

Table A1. Selected Genes Associated With Treatment Implications and Predisposition to Prostate Cancer

Acknowledgment

Nosotros give thanks Mark Robson, Doc, for his review and comments on this article.

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