Role of Genetic Counseling Nurse in Breast Cancer. Sung-Won Kim, MD, PhD, FACS CEO & President Daerim St. Mary s Hospital

Size: px

Start display at page:

Download "Role of Genetic Counseling Nurse in Breast Cancer. Sung-Won Kim, MD, PhD, FACS CEO & President Daerim St. Mary s Hospital"

Richard Foster
5 years ago
Views:

1 Role of Genetic Counseling Nurse in Breast Cancer Sung-Won Kim, MD, PhD, FACS CEO & President Daerim St. Mary s Hospital

2 What is hereditary breast cancer? Hereditary (5-10%): Mutated phenotype of a specific gene segregating with a Mendelian inheritance pattern in families Familial (15-20%): one or more 1 st and/or 2 nd -degree relatives of the proband affected by breast cancer, in the absence of Mendelian inheritance and/or of an identified cancer-causing germline mutation of a specific gene Sporadic (70-80%): lack of breast cancer among a patients 1 st and/or 2 nd -degree relatives

3 Genes related to HBC

4 Penetrance of BRCA mutation Western Data: Antoniou et al. Am J Hum Genet 2003 BRCA1-mutation Carrier Breast 65% 39% BRCA2-mutation Carrier 45% Ovary Breast Ovary 11%

5 Options for BRCA Mutation Carriers 1. Life style modification 2. Surveillance option 3. Chemoprevention option Aggressive but Better Prevention! 4. Risk-reducing surgery

6 Breast awareness starting at age 18 y. Clinical breast exam, every 6 12 mo, starting at age 25 y. Breast screening Age y, annual breast MRI screening Age y, annual mammogram (w/ Tomo) and breast MRI screening Age >75 y, management should be considered on an individual basis. Discuss option of risk-reducing mastectomy Recommend RRSO typically between 35 and 40 y, and upon completion of child bearing. it is reasonable to delay RRSO until age y in patients with BRCA2 mutations who have already maximized their breast cancer prevention Without RRSO: TV-US and serum CA-125 may be considered at the clinician s discretion starting at age y. Consider risk reduction agents as options for breast and ovarian cancer

7 What is a genetic counselor? Genetic counselors who specialize in oncology evaluate family histories of cancer and determine whether patients or their relatives should be tested for gene mutations that can cause hereditary oncologic syndromes, and which tests they should have. After interpreting the results of those blood tests, the counselors help patients make decisions about prevention or management of their cancers, and also offer psychosocial support. In US: a certified genetic counselor is a professional who has completed a 2-year master of science degree focused on the study of both genetics and counseling, and then earned certification from the American Board of Genetic Counseling

8 JCO 2010

9 Evaluation of Patients with Possible Hereditary Predisposition Pedigree & Risk Assessment (Risk > 10%) Pre-test Counseling Informed consent Blood acquisition Genetic Testing & Test Result Interpretation Post-test Counseling Result discussion Family member counseling

10 Pre-test counseling

11 Post-test counseling

12 Role of ON in GC Depending on their level of training oncology nurses will have varying levels of involvement in genetic counseling. Many nurses play a facilitator role recognizing an individual s need for genetic evaluation and then making a referral to a counselor Some advanced practice nurses participate in the actual counseling Advanced practice nurses with specialized training in clinical cancer genetics and genomics and cancer predisposition testing may be involved in the clinical application of cancer genetics, including genetic counseling and education.

13 Role of ON in GC 1. Diagnosis of hereditary breast cancer 2. Building a knowledge base wrong surgery or the wrong type of screening because of misinterpretation of [the implications of] test results I worry about patients who have bad family histories but normal test results, and their doctors are falsely reassuring them that everything is fine. 3. Beyond medical support GC also involves protecting patients from some of the social and financial repercussions of carrying a hereditary cancer gene. helping individuals overcome barriers to access.

14 Genetic discrimination Korea (since Jan 1, 2005) Bioethics and Biosafety Act Section 6 Clause One should not be discriminated against in education, employment, promotion, insurance, or any other social activity based on genetic information 2. Unless otherwise required by another law/regulation, one cannot coerce a person to take a genetic test or submit a genetic test result 3. Medical institutions should not include genetic test results in the electronic medical records of patients unless requested by another medical institution and is deemed necessary for patient care (diagnosis, treatment, etc). This is allowed only if measures have been taken to ensure patient health information protection.

15 Genetic discrimination United States The Genetic Information Nondiscrimination Act of 2008 (Pub.L , 122 Stat. 881, enacted May 21, 2008, GINA, pronounced Gee-na), is an Act of Congress in the United States designed to prohibit the use of genetic information in health insurance and employment. However, the law does not cover life insurance, disability insurance and long-term care insurance.

16 Issues in the era of whole gene sequencing In clinical exome and genome sequencing, how do you deal with incidental or secondary findings that are unrelated to the indication for ordering the test but are of medically significant value? Which findings do we report if we ever do? Who s responsible for keeping up-to-date with the rapidly changing field of genetics? What if a variant of uncertain significance today in six months is shown to be pathogenic?

17 Reclassification of BRCA1 L1780P as pathogenic mutation

18 ACMG 2016 Statement on Reporting of Secondary Findings in Clinical Exome and Genome Sequencing Purpose: to promote standardized reporting of actionable information from clinical genomic sequencing A secondary findings minimum list of 59 medically actionable genes - recommended for return in clinical genomic sequencing Goal was to identify and manage risks for selected highly penetrant genetic disorders through interventions aimed at preventing or significantly reducing morbidity and mortality Known pathogenic and expected pathogenic sequence variants in the 59 genes including BRCA1&2, TP53, APC, MEN1 and more Individuals undergoing these clinical tests had an option to opt-out of receiving secondary findings following appropriate counseling

20 Histories of 23andMe

21 BRCA1/2: 3 AJ founder mutation

22 스포츠한국 ( 월 ), P7

23 Highlights of Korean Hereditary Breast Cancer Study; 10-year experience! Sung-Won Kim, MD, PhD, FACS CEO & President Daerim St. Mary s Hospital

24 Important events in Korea 1994 BRCA BRCA BRCA testing: Reimbursement start! 2007~10 KOHBRA Study I 2010~13 KOHBRA Study II BRCA testing: Reimbursement expanded RRSO: Reimbursement start! Angelina Jolie RRM in NY Times Angelina Jolie RRSO in NY Times Reconstruction after TM: Reimbursement start! CPM: Reimbursement start! Reconstruction after CPM: Reimbursement start!

Korean Hereditary Breast Cancer (KOHBRA ) Study KOHBRA I : 2007.5.

26 Korean Hereditary Breast Cancer (KOHBRA ) Study KOHBRA I : KOHBRA II : Multi-centre study which is conducted by KBCS (40 centers) Grant: the National R&D Program for Cancer Control

KOHBRA Study I Korean Breast Cancer Study

27 KOHBRA Study I Korean Breast Cancer Study Group (KBCSG) National Study (35 centers) ~ Goal (N=2250) Part I: Family Hx(+) Part II: FHx(-) & high risk group 1.Age at Dx.<40 2.Coexistence of ovary ca. 3.Male breast ca. 4.Bilateral breast ca. Part III: family member of BRCA(+) Part IV: Female from Part I, II, III (ovary ca prevalence)

28 Study Design of KOHBRA HIGH-RISK GROUP OF FAMILIAL BREAST CANCER Informed Consent (+) Start Annual checking of patient s status with KBCS data Breast Cancer Patient Familial Non-Familial 1 Year 2 Year 3 Year 4 Year Family Members of Patients Informed Consent (-) Reporting Results Genetic / Nutritional Counseling Baseline Examination Questionnaires survey Anthropometric measurement Blood sampling BRCA/CA125 test Collection of clinical data 1 year F/U 3 year F/U Questionnaires survey Anthropometric measurement Blood sampling Collection of clinical data Questionnaires survey Anthropometric measurement Blood sampling Collection of clinical data

29 KOHBRA Study 2 (2010.6~2013.5) Development of Korean BRCA Prediction Model Characterization of clinical phenotype and discovery of novel prognostic factors for BRCA associated breast cancer Part I (Risk prediction) Part 2 (Treatment) Development of nationwide network of genetic counseling Part 4 (Genetic counseling) Part 3 (Prevention) Identification of environmental and genetic modifiers of BRCA1/2 mutation

30 Enrollment ( ~ ) Subgroups Total Total enrollment 3237 Familial breast cancer patients 1342 High-risk non-familial breast cancer 1342 Family members of carriers 553 Banking (WB, DNA, Serum, Plasma) 3183 BRCA Carriers 684

31 KOHBRA Enrollment

32 KOHBRA Study Publications (52 publications) JAMA, Nature, Nature Genetics, JCO, Hum Mutation, PLoS Genetics

33 Risk assessment for HBOC in Korea KOHBRA Study

34 BRCA1/2 Mutation risk assessment model Empirical model BRCA mutation risk Myriad I model Couch model Penn II model Myriad II Family history assessment tool Manchester model Australian LAMBDA model NCI model Spanish model/finish model Statistical model BRCA mutation risk Breast cancer risk BRCAPRO Yale University model The International Breast Cancer Intervention Study (IBIS) model The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) 34

35 To evaluate the accuracy of the BRCAPRO and Myriad II models in Korean breast cancer patients who underwent comprehensive BRCA1/2 genetic testing (n=236) Kang E and KOHBRA Study group et al. Breast Cancer Res Treat 2012;134:

36 Comparison of observed and expected mutation proportion Overall (n=236) Observed Mutation (%) BRCAPRO Expected mutation (%) Observed Mutation (%) Myriad II Expected mutation (%) * * < 10% * * 10% * Performance of prediction models at carrier probability of 10% Model Sensitivity (%) Specificity (%) PPV (%) NPV (%) AUC BRCAPRO Myriad II

37 KOHBRA BRCA Risk Calculator (KOHCal) For familial breast cancer patients For non-familial breast cancer patients Age at diagnosis? Bilateral breast cancer? Have you ever been diagnosed with ovarian cancer? Or TNBC? How many in your family has been diagnosed with BC or OC?

38 KOHBRA BRCA Risk Calculator (KOHCal)

39 Breast and ovarian cancer risks associated with BRCA mutations KOHBRA Study

40 Penetrance of BRCA mutation Western Data: Antoniou et al. Am J Hum Genet 2003 BRCA1-mutation Carrier Breast 65% 39% BRCA2-mutation Carrier 45% Ovary Breast Ovary 11%

41 Breast cancer risk for Korean women with germline mutations in BRCA1 and BRCA2 Analyses were based on phenotype and genotype data on 12,8 20 people from 151 families with BRCA1 mutation carrier prob ands and 225 families with BRCA2 mutation carrier probands Average age-specific cumulative risks of breast cancer were calc ulated using a modified segregation analysis method Park B and KOHBRA Study group et al. BCRT 2015

42 Penetrance of BC in female BRCA1/2 mutation carriers

43 Estimated 10y BC risks for BRCA carriers

44 Identification of environmental and genetic modifiers of BRCA1/2 mutation KOHBRA Study

45 Personalized risk assessment Risk may vary by Mutation Modifier genes Modifier exposures Ethnicity

46 Mutation specific penetrances to age 70 Rebbeck et al. JAMA 2015

47 Meta-analysis of non-genetic risk modifiers Friebel et al. JNCI 2014

48 Association of Type and Location of BRCA1 and BRCA2 Mutations with Risk of Breast and Ovarian Cancer Rebbeck TR and CIMBA Consortium Et al. JAMA 2015 BRCA1 BRCA2

49 Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the KOHBRA Study Ko et al. Am J Clin Nutr Food-frequency questionnaire

50 The association between the dietary diversity and risk of breast cancer in case-control study design Total population Restricted population Dietary diversity N of N of breast cancer (numbers of food items) HR (95% CI) participants cases N of N of breast cancer HR (95% CI) participants cases Carriers N=491 N=370 N=273 N=152 Vegetables 1Q (0-4) Q (5-8) (0.75, 1.36) (0.55, 1.35) 3Q (9-12) (0.64, 1.23) (0.44, 1.24) 4Q (13-25) (0.73, 1.43) (0.43, 1.30) p-trend Fruits 1Q (0-3) Q (4-6) (0.87, 1.63) (0.61, 1.73) 3Q (7-9) (0.87, 1.58) (0.80, 2.04) 4Q (10-12) (0.91, 1.76) (0.56, 1.71) p-trend Meat 1Q (0) Q (1) (0.76, 1.38) (0.64, 1.68) 3Q (2) (0.75, 1.61) (0.77, 2.17) 4Q (3-10) (0.92, 1.99) (1.13, 3.44) p-trend Seafood 1Q (0-1) Q (2) (0.80, 1.54) (0.70, 2.03) 3Q (3-4) (0.78, 1.39) (0.71, 1.82) 4Q (5-17) (0.59, 1.11) (0.51, 1.40) p-trend Soybean products 1Q (0-1) Q (2) (0.89, 1.67) (0.68, 1.76) 3Q (3) (0.72, 1.34) (0.45, 1.14) 4Q (4-5) (0.45, 1.06) (0.19, 0.79) p-trend

52 Gene-environment interaction for the combination of BRCA mutation and diet diversity among affected cases in the KOHBRA study ( ): Case-only study Dietary diversity (numbers of food items) BRCA carriers (N=370), N (%) Total affected cases (N=2,002) Non-BRCA carriers (N=1,632), N (%) COR 1 (95% CI) BRCA carriers (N=152) N (%) Restricted affected cases 2 (N=998) Non-BRCA carriers (N=846), N (%) COR * (95% CI) Vegetables 1Q (0-4) 83 (22.4) 348 (21.3) (28.3) 196 (23.2) Q (5-8) 104 (28.1) 474 (29.0) 0.87 (0.63, 1.20) 45 (29.6) 276 (32.6) 0.73 (0.46, 1.16) 3Q (9-12) 80 (21.6) 390 (23.9) 0.78 (0.55, 1.11) 30 (19.7) 191 (22.6) 0.68 (0.40, 1.15) 4Q (13-25) 103 (27.8) 420 (25.7) 0.86 (0.61, 1.22) 34 (22.4) 183 (21.6) 0.75 (0.44, 1.29) P for trend Fruits 1Q (0-3) 91 (24.6) 395 (24.2) (23.0) 234 (27.7) Q (4-6) 82 (22.2) 347 (21.3) 1.02 (0.73, 1.43) 29 (19.1) 192 (22.7) 0.98 (0.57, 1.68) 3Q (7-9) 103 (27.8) 475 (29.1) 0.94 (0.68, 1.30) 51 (33.6) 232 (27.4) 1.46 (0.90, 2.37) 4Q (10-12) 94 (25.4) 415 (25.4) 0.91 (0.65, 1.28) 37 (24.3) 188 (22.2) 1.30 (0.77, 2.20) P for trend Meat 1Q (0) 239 (64.6) 1,061 (65.0) (55.3) 471 (55.7) Q (1) 58 (15.7) 304 (18.6) 0.83 (0.61, 1.15) 25 (16.5) 188 (22.2) 0.71 (0.44, 1.16) 3Q (2) 33 (8.9) 115 (7.1) 1.25 (0.82, 1.92) 20 (13.2) 82 (9.7) 1.31 (0.75, 2.29) 4Q (3-10) 40 (10.8) 152 (9.3) 1.05 (0.69, 1.60) 23 (15.1) 105 (12.4) 1.13 (0.64, 1.98) P for trend Seafood 1Q (0-1) 106 (28.7) 427 (26.2) (26.3) 245 (29.0) Q (2) 61 (16.5) 274 (16.8) 0.88 (0.61, 1.25) 26 (17.1) 132 (15.6) 1.25 (0.72, 2.15) 3Q (3-4) 98 (26.5) 455 (27.9) 0.82 (0.60, 1.12) 38 (25.0) 229 (27.1) 1.00 (0.61, 1.63) 4Q (5-17) 105 (28.4) 476 (29.2) 0.76 (0.55, 1.06) 48 (31.6) 240 (28.4) 1.15 (0.70, 1.89) P for trend Soybean products 1Q (0-1) 68 (18.4) 239 (14.6) (23.0) 139 (16.4) Q (2) 112 (30.3) 428 (26.2) 0.90 (0.64, 1.27) 40 (26.3) 216 (25.5) 0.72 (0.43, 1.20) 3Q (3) 153 (41.4) 772 (47.3) 0.63 (0.45, 0.88) 65 (42.8) 400 (47.3) 0.60 (0.37, 0.96) 4Q (4-5) 37 (10.0) 193 (11.8) 0.57 (0.36, 0.91) 12 (7.9) 91 (10.8) 0.49 (0.24, 1.02) P for trend

53 Genetic training program for ON in Korea In US: a certified genetic counselor is a professional who has completed a 2-year master of science degree focused on the study of both genetics and counseling, and then earned certification from the American Board of Genetic Counseling In Korea, there are several programs for training genetic counselors. The Korean Breast Cancer Society established training program for hereditary breast and ovarian cancer GC program since 2011 for 2 to 3-day course. And since 2014 the Korean Medical Genetic Association started to certify the genetic counselor and in 2018 KMGA certified GC program as a Master s degree course. (Ulsan University, Gacheon Uinv., Ajou univ.)

54 Virtual Counselor Computer Animation Program

55 Text Book and Genetic Counseling Manual

56 Asian BRCA (ABRCA) Consortium Participants Korea (KOHBRA study, headquarter), Japan, Hong Kong, Malaysia, Indonesia, China, Singapore Objectives To share the knowledge of HBOC in Asian country To improve the quality of care of HBOC patients in Asia To collaborate for researches on HBOC in Asia Research collaboration BRCA registry Blood and tissue banking Clinical practice guideline

58 Changing patterns in the management of HBOC in Korea Angelina Jolie Effect

59 Angelina Jolie effect in Korea Survey: Answer from 70 doctors (69 surgeons, 1 medical oncologist) 2012 N(%) 2015 N(%) p Family Hx taking 62(88.6) 68(97.1) 0.63 Pedigree drawing 19(27.1) 34(48.6) 0.00 Ix. BRCA testing Br/Ov cancer famiy hx. 42(60.0) 67(95.7) 0.00 Early onset (<40) 42(60.0) 64(91.4) 0.00 Bilateral BC 42(60.0) 63(90.0) 0.00 Male BC 29(41.4) 45(64.3) 0.00 Multiple cancer 19(27.1) 37(52.9) 0.00 TPN BC (<60) 1(1.4) 7(10.0) 0.03 OC (<50) 16(22.9) 27(38.6) 0.00

60 Angelina Jolie effect in Korea (cont d) 2012 N(%) 2015 N(%) p Genetic counseling GC always done before testing 34(48.6) 62(88.6) 0.00 If BRCA+ family member testing 57(81.4) 69(98.6) 0.00 Surveillance and prevention of unaffected carrier 0.00 Breast MR for BC screening 28(40.0) 42(60.0) 0.00 Chemoprevention for BC rec. 20(28.6) 35(50.0) 0.00 RRM rec. 11(15.7) 23(32.9) 0.00 RRCM rec. 10(14.3) 26(37.1) 0.00 RRSO rec. 24(34.3) 47(67.1) 0.00 Chemoprevention for OC rec. 5(7.1) 10(14.3) 0.06

61 Annual changes of BRCA1/2 Gene testing Health Insurance Review & Assessment Servi BRCA BRCA

62 BRCA testing Reimbursement expanded Angelina Jolie Double mastectomy

63 Risk-reducing surgery Answers from 28 institutions Healthy BRCA carriers (n=126) RRBM 1 1 RRSO 1 2 BRCA carriers with unilateral BC (n=717) RRCM 4 (3 inst) 20 (8 inst) RRSO 16 (7inst) 75 (15 inst)

64 Challenges in Next Decade NGS-based gene panel testing DTC based population based BRCA screening BRCA prevalence in TPN breast cancer patient Clinical trial Working with international consortium

65 Collaboration Defeats Cancer!

66 Acknowledgement Mentor Kuk Jin Choe Dong-Young Noh KOHBRA Study Group Min Hyuk Lee Sei Hyun Ahn Sue K. Park Eunyoung Kang ABRCA Consortium Seigo Nakamura Ava Kwong Soo-Hwang Teo Daerim St. Mary s Hosp Dong Won Kim Bo Young Kang Jiwon Jeong Kyung Min Lha Yun Jeong Lee Ha Na Nam

67 Thank you for your attention!

Risk-reducing Surgery in BRCA mutation carriers

Risk-reducing Surgery in BRCA mutation carriers Daerim St. Mary s Hospital Department of Surgery, Breast Care Center Hereditary Breast Ovarian Cancer Clinic Sung-Won Kim, MD, PhD, FACS Overview of HBOC