Germline Mutations Hereditary Breast and Ovarian Cancer Risk and Management Issues
|
|
- Audra Cunningham
- 6 years ago
- Views:
Transcription
1 Germline Mutations Hereditary Breast and Ovarian Cancer Risk and Management Issues Jeffrey N. Weitzel, M.D. Cancer Screening & Prevention Program
2 Risk Factors for Breast Cancer Aging Family history Early menarche Late menopause Nulliparity Estrogen/Prog use Dietary factors (e.g., alcohol)
3 Genetics and the Brave New World - or is it old world?
4 How Much Breast and Ovarian Cancer Is Hereditary? 15% -20% Breast Cancer 5% 7% ~10% Sporadic Family clusters Hereditary Ovarian Cancer
5 Timeline of Important Events in DNA Patenting (Top) and the Discovery and Use of Genes Conferring Susceptibility to Breast and Ovarian Cancer (Bottom) Kesselheim A and Mello M. N Engl J Med 2010; /NEJMp
6 BRCA1- and BRCA2-Associated Cancers: Lifetime Risk Breast cancer 50%-85% (often early age at onset) Second primary breast cancer 40%-60% Ovarian cancer 15%-45% Absolute risk likely to be higher than 10% - Prostate cancer Absolute risk 10% or lower - Male breast cancer - Fallopian tube cancer - Pancreatic cancer
7 BRCA1 and BRCA2 On chromosomes 17 and 13, respectively Autosomal dominant transmission Proteins have a role in genomic stability >2,000 different mutations, polymorphisms, and variants distributed over both genes BRCA1 Nonsense Missense Splice-site Breast Cancer Information Core
8 8
9 BRCA: Selected Examples of Founder Mutations Population BRCA1 Mutations BRCA2 Mutations Ashkenazi Jewish Icelandic 185delAG 5382insC 6174delT 999del5 British 6-kb duplication of exon del4 6503delTT Dutch (Netherlands) Chinese Russian African A. 2804delAA Large deletions of exons 13 & delG 5382insC 4153delA 1832del5 5296del4 Hispanic 185delAG deletion exons insT
10 Inherited Genomic Rearrangements of BRCA1 and BRCA2 35/300 (12%) sequence negative high risk families Other: CHEK2 n=14 (5%) TP53 n=3 (1%) Walsh et al, JAMA 295: , 2006
11 Genomic BRCA Rearrangements in a High Risk Clinic Population Sample: Two hundred fifty-one affected high-risk clinic probands Evaluated with commercial sequencing for BRCA1 and BRCA2 All without point mutations were screened by MLPA Results: 36 (26%) BRCA point mutations and 8 (6%) genomic rearrangements among the 136 non-ashkenazi Jewish (AJ) probands Forty-five of 47 mutations detected in 115 AJ probands were founder point mutations; no genomic rearrangements were identified In the non-aj probands, genomic rearrangements constituted 18% of all identified BRCA mutations The data suggest that genomic rearrangement testing be considered in all non-aj women with an estimated mutation prevalence >10% Palma et al. Cancer Res 2008;68:
12 k Comprehensive genetic testing includes full sequencing of BRCA1/BRCA2 and detection of large genomic rearrangements.
13 Influence of BRCA1 Genotype on Histopathology in Breast Cancer (BC) Less likely to express estrogen receptor or Her2/neu Have a high nuclear grade Show less tubule formation Have a higher mitotic count Medullary histology more common (~ 6%) More BRCA1 mutations in triple negative DCIS is less associated with BRCA1 than BRCA2 BRCA testing may be appropriate for triple negative BC or early onset DCIS, especially if family history of BC and/or OC Eisinger et al. Cancer Res 56:471, 1996; Claus et al, JAMA 293: , 2005; Breast Cancer Linkage Consortium. Lancet 349:1505, 1997; Kandel (ASCO), 2006
14 Contribution of known genes to explaining familial aggregation of breast cancer BRCA1 BRCA2 TP53 PTEN ATM CHEK2,BRIP1,PALB2 CASP8 Other familial risk factors (genes, environment) 8 WGA SNPs
15
16 Li-Fraumeni Syndrome Bilateral Breast, Breast, 40 Osteosarcoma, 42 Leukemia, 33 TP53-mutation carrier Affected with cancer Breast, 35 Soft tissue sarcoma, 7 Brain tumor, 32 Leukemia, 6 ASCO
17 Cowden Syndrome Pedigree Multinodular goiter, dx 25 Follicular thyroid cancer, dx 35 Trichilemmomas, dx 21 Breast cancer, dx 35 Noncarrier Affected Risk for uterine, but not ovarian ca in CS Macrocephaly Papillomatous papules Multinodular goiter, dx 22 Eng C. J Med Genet. 2000;37:
18 Emerging Breast Cancer Phenotype in Women with TP53 Germline mutations Cohort of TP53 Carriers N ER+ Her2/neu+ LiFE Consortium 32 84% 63% Masciari et al. BCRT 2012 UK 9 83% Wilson et al. J Med Genet 2010 MDACC/Chi 30 70% 67% Melhem-Bertrandt et al. Cancer 2012 Women < 40 BC, unselected for FHx % 22-33% Collins et al. BCRT 2011; Gonalez- Angulo et al. Cancer 2012
19 Cancer Screening & Prevention Program Genetic Predisposition Testing Is a Multi-Step Process Identify at-risk patients Provide pretest counseling Obtain informed consent Select and offer test Disclose results Provide post-test counseling and follow-up
20 Estimating Cancer Risk Family History Empiric Data Genetic Testing
21 Comparing Breast Cancer Risk Assessment Models Beth Breast, 27 Diana Breast, 32 Cindy, 39 Age at menarche: 15 Previous breast biopsies: 0 Atypical hyperplasia: unknown Age at birth of 1st child: none First degree relatives BC: 1 Model Gail Claus General population Breast Cancer Risk (%) by Age Genetic: Predicted probability of carrying a BRCA mutation = 20% for affected sister, 10% for proband; breast cancer risk 50-80% if carrier 7
22 Family Structure Limited Paternal Family Structure Adequate Family Structure for both Maternal and Paternal Lineage 88 y d. 73 y 85 y 87 y 88 y d. 73 y 85 y 87 y 62 y 55 y d. 36 y MVA 60 y 57 y 65 y d. 55 y 62 y 55 y 58 y 60 y 57 y 65 y 55 y Br 47 Breast Cancer Br 47 Breast Cancer Male Female Affected Female Deceased Deceased Patient seen for Risk Assessment Weitzel et al. JAMA 297(2007)
23
24 HEREDITARY BREAST AND OVARIAN CANCER Br- Pm Br- 45 ex9-12del + 81 Br Br- Pm Pr- 50 Br Ov
25 Clinical Management of BRCA Mutation-Negative Patients Negative BRCA1 and/or BRCA2 test result NO Member of family w/ known BRCA1 or BRCA2 mutation? YES Emphasize empirically increased risk of breast and/or ovarian cancer Provide individualized risk-management plan Emphasize risk of sporadic cancer Encourage adherence to population screening guidelines
26 Clinical Management of BRCA Mutation-Positive Patient Cancer Screening & Prevention Program Possible testing for other adult relatives Positive BRCA1 or BRCA2 test result Prophylactic surgery Lifestyle changes Increased surveillance Chemoprevention
27 Dense Breast Tissue Size? Time Mammo
28 MRI and Breast Cancer Detection in BRCA Carriers - Sensitivity N with mutations Invasive cancers % by MRI % by mammogram Warner (2004) Kriege (2004) MARIBS (2005) % 31% % 33% % 23% TOTAL % 30% Breast MRI may be considered the standard of care for high risk patients
29 Sensitivity of mammography and MRI for DCIS detection Mammography MRI p value * All DCIS (n=167) 93 (56%, 47 63%) 153 (92%, 86 95%) < All non-high-grade DCIS (n=78) 47 (60%, 48 71%) 66 (85%, 74 91%) Low grade (n=44) 27 (61%, 45 75%) 35 (80%, 64 90%) 0 13 Intermediate grade (n=34) 20 (59%, 41 75%) 31 (91%, 75 98%) All high-grade DCIS (n=89) 46 (52%, 41 62%) 87 (98%, %) < High grade, with necroses (n=55) 34 (62%, 48 74%) 54 (98%, 89 99%) < High grade, without necroses (n=34) 12 (35%, 20 53%) 33 (97%, %) < Data are n (%, 95% CI). * Calculated by the McNemar's test. Non-high-grade without necroses. Non-high-grade with necroses. Kuhl, C. K., Schrading, S., Bieling, H. B., Wardelmann, E., Leutner, C. C., Koenig, R., et al. (2007). MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet, 370(9586),
30 Is risk reduction mastectomy (RRM) effective? Skin-Sparing Mastectomy With Immediate Reconstruction Comparison of 214 high risk women who underwent RRM ( ) to sister controls: 3 cases BC observed vs expected = 92% Risk Reduction Hartmann L. et al, NEJM, 340:77, 1999; JNCI 93:1633, 2001 Study of 483 BRCA carriers: >90% risk reduction Rebbeck, T.R., et al. JCO 22:1055, 2004
31 New Primary Cancer Risk and Modifiers Among 491 BRCA Carriers 10-year contralateral breast cancer risk 43.4% for BRCA1; 34.6% for BRCA2 Age 50 at diagnosis: HR 0.63; 95% CI Tamoxifen use: HR 0.59; 95% CI Oophorectomy: HR 0.44; 95% CI year ovarian cancer risk after breast cancer: 12.7% for BRCA1, 6.8% for BRCA2 (p=0.03) Ovarian cancer was the cause of death in 25% of the Stage I breast cancer patients Metcalfe et al. J Clin Oncol 2004, 22: Gyn Onc 2005; 96:
32 Options for breast cancer patients with BRCA mutations Surgical options for the breast therapeutic mastectomy versus breast conservation therapy on affected breast risk reduction mastectomy on contralateral breast Hormonal risk reduction options BSO tamoxifen Screening mammography MRI
33 Decisions, decisions Oncologic Consultation Treatment Genetic Cancer Risk Assessment Prevention
34 Options for BRCA1, BRCA2 Carrier Prophylactic Oophorectomy Chemoprevention CA125 Screening CASH study. N Engl J Med 316:650, 198 Rosenberg L et al. Am J Epidemiol 139:654, Ursin G et al. Cancer Re 57:3678, Narod et al, NEJM 339:424, 1998Narod SA, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 carriers. J Natl Cancer Inst 2002;94:
35 Penetrance of Ovarian, Fallopian Tube, and Peritoneal Cancer Among BRCA Mutation Carriers Finch, A. et al. JAMA 2006;296:
36 Oophorectomy Reduces Ovarian Cancer, Breast Cancer, and all cause mortality Greatest breast cancer risk reduction was among BRCA1 mutation carriers without a prior dx of breast cancer who had their oophorectomy < age 50 HR: 0.15 (95% CI )
37 Oophorectomy Reduces All-Cause Mortality
38 Genetic status is on the cusp of helping to determine composition of breast and ovarian cancer treatment regimens
39 Poly (ADP-ribose) polymerase (PARP) A key regulator of DNA damage repair processes Involved in DNA base-excision repair (BER) Binds directly to DNA damage Produces large branched chains of poly(adp-ribose) Attracts and assists BER repair effectors XRCC1 PNK Polß Lig3
40 PARP inhibition and tumor-selective synthetic lethality DNA damage (SSBs) DNA replication (accumulation of DNA DSBs) PARP PARP inhibition Normal cell with functional HR pathway HR-deficient tumor cell (e.g. BRCA 1/2 -/- ) HR-mediated DNA repair Cell survival Tumor-selective cytotoxicity Cell death Impaired HRmediated DNA repair DSB, double-strand break; HR, homologous recombination SSB, single-strand break Farmer H et al. Nature 2005;434: Bryant HE et al. Nature 2005;434: McCabe N et al. Cancer Res 2006;66:
41 PARP inhibitors in cancer therapy Agent Company Single / Combination therapy AG Pfizer (New York, NY) Route of administr ation Disease Single IV Advanced BC and OC Clinical status Phase 1 in solid tumors, phase 2 in BC and OC AZD2281 (Olaparib) ABT-888 (Veliparib) BSI-201 (Iniparib) GPI AstraZeneca/Ku DOS (London, UK) Abbott Laboratories (North Chicago, IL) Sanofi-Aventis (Bridgewater, NJ) MGI Pharma (Bloomington, MN) Single, combinations with carbo/paclitaxel or paclitaxel alone Combination with carbo, temozolomide, or cisplatin/vinorelbine Oral Advanced BC and OC Phase 2, 3 ongoing Oral Advanced BC Phase 1, 2, 3 ongoing Gemcitabine/carboplatin IV Triple-negative BC Combination with temozolomide Phase 2, 3 ongoing Oral Solid tumors Phase 1 planned
42 Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer: Best % change from baseline in target BC lesions by prior chemotherapy Olaparib 400 mg bid cohort ORR, n (%) 11 (42) CR, n (%) 1 (4) PR, n (%) 10 (39) Previous anthracycline, taxane and capecitabine Best % change from baseline * * * * * Increasing tumor shrinkage * *Prior platinum Tx Tutt et al. Lancet 2010
43 Protocol NCI #8264: ABT-888 +/- Carbo Adv/Mets BRCA- Breast Cancer Safety Lead-In 21 patients ABT mg BID >2 cycles ABT mg BID + Carbo AUC=5 Post-progression Endpoints: BRCA1 vs. BRCA2 RECIST Criteria PFS ABT-888 single agent; post-progression for combination Safety & Tolerability, Pharmacokinetics Correlative studies will include biomarkers of PARP and carboplatin effect, as well as prospective analyses of mechanism(s) of resistance in vivo selection for BRCA reversion mutants that restore the reading frame and functional domains such as HRR may be one mechanism of drug resistance
44 Proportions ovarian, fallopian tube, or peritoneal cancer patients with respective germ-line loss-of-function mutations Walsh T et al. PNAS 2011;108:
45 Weitzel et al. Genetics, Genomics, and Cancer Risk Assessment: State of the Art and Future Directions in the Era of Personalized Medicine. CA Cancer J Clin 2011;61:
46 Clinical Utility and professional mediation of genetic testing directed by HCP directed by individual clinical utility accepted high penetrance DTC testing clinical utility unclear intermediate penetrance low penetrance variants American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. J Clin Oncol, 2010.
47 Cancer Screening & Prevention Program Breast and Ovarian Cancer Screening and Prevention Key advances and evidence for advice: There are advances in protocols for screening (MRI), risk reduction (RRSO, RRM), and targeted treatment Warner et al, 2004; Kriege et al, 2004; Rebbeck et al, 2002, Kauff et al, 2002; Weitzel et al, 2007 GCRA influences surgical decisions in a risk-appropriate way and should be considered for women with newly diagnosed early stage breast cancer and suspicion of BRCA gene mutation Timing of GCRA in the sequence of events in cancer diagnosis and treatment is dependent on both patient and provider variables and limitations Weitzel et al, 2003; Schwartz et al, 2004, 2005.
48 Cancer Screening & Prevention Program Breast and Ovarian Cancer Screening and Prevention Key advances and evidence for advice: BRCA testing for early onset DCIS, and for single cases of BC <50 years if limited family structure; <60 if triple negative Claus et al, 2005; Kandel et al, 2006; Weitzel et al, 2007 Large rearrangements account for a significant proportion of high risk families without sequence detected BRCA mutations Walsh et al, 2006; Weitzel et al, 2007; MGL 2012 Documented efficacy of interventions for BRCA mutation carriers drives medical necessity and liability issues, making GCRA a standard of care GCRA along with risk reduction interventions are cost-effective tools for increasing quality-adjusted life
Germline Mutations Hereditary Breast and Ovarian Cancer Risk and Management Issues
Germline Mutations Hereditary Breast and Ovarian Cancer Risk and Management Issues Jeffrey N. Weitzel, M.D. Cancer Screening & Prevention Program Timeline of Important Events in DNA Patenting (Top) and
More informationGermline Mutations Hereditary Breast and Ovarian Cancer Risk and Management Issues
Germline Mutations Hereditary Breast and Ovarian Cancer Risk and Management Issues Jeffrey N. Weitzel, M.D. Cancer Screening & Prevention Program Risks Related to Breast Cancer Advancing Age! Early Menarche!
More informationGenetics of Breast and Ovarian Cancer: Risk Assessment, Screening, and Risk Reduction
Genetics of Breast and Ovarian Cancer: Risk Assessment, Screening, and Risk Reduction Forum INCA-ASCO sobre Cancer Hereditario e Predisposicao Genetica ao Cancer Jeffrey N. Weitzel, M.D. Professor of Oncology
More informationHereditary Breast and Ovarian Cancer Rebecca Sutphen, MD, FACMG
Hereditary Breast and Ovarian Cancer 2015 Rebecca Sutphen, MD, FACMG Among a consecutive series of 11,159 women requesting BRCA testing over one year, 3874 responded to a mailed survey. Most respondents
More informationThe Genetics of Breast and Ovarian Cancer Prof. Piri L. Welcsh
The Genetics of Breast Piri L. Welcsh, PhD Research Assistant Professor University of Washington School of Medicine Division of Medical Genetics 1 Genetics of cancer All cancers arise from genetic and
More informationHEREDITY & CANCER: Breast cancer as a model
HEREDITY & CANCER: Breast cancer as a model Pierre O. Chappuis, MD Divisions of Oncology and Medical Genetics University Hospitals of Geneva, Switzerland Genetics, Cancer and Heredity Cancers are genetic
More informationPredictive and Diagnostic Testing for Cancer in Women. Aparna Rajadhyaksha MD
Predictive and Diagnostic Testing for Cancer in Women Aparna Rajadhyaksha MD Hereditary Cancer s in Women BRCA1 &2 Other Breast Cancer Genes Li Fraumeni PTEN CHEK2 BRCA1&2 t BRCA1 is part of a complex
More informationHereditary Gynecologic Cancer 15 Years of Progress
Hereditary Gynecologic Cancer 15 Years of Progress Bethan Powell, M. D. Kaiser Permanente UCSF Gynecologic Cancer Risk Program Hereditary Gynecologic Cancer Syndromes BRCA 1 and 2: ovarian Lynch: ovarian/endometrial
More informationJill Stopfer, MS, CGC Abramson Cancer Center University of Pennsylvania
Jill Stopfer, MS, CGC Abramson Cancer Center University of Pennsylvania Aging Family history Early menarche Late menopause Nulliparity Estrogen / Progesterone use after menopause More than two alcoholic
More informationGermline Genetic Testing for Breast Cancer Risk
Kathmandu, Bir Hospital visit, August 2018 Germline Genetic Testing for Breast Cancer Risk Evidence-based Genetic Screening Rodney J. Scott Demography in New South Wales (total population ~ 7,000,000)
More informationHBOC Syndrome A review of BRCA 1/2 testing, Cancer Risk Assessment, Counseling and Beyond.
HBOC Syndrome A review of BRCA 1/2 testing, Cancer Risk Assessment, Counseling and Beyond. Conni Murphy, ARNP Cancer Risk Assessment and Genetics Program Jupiter Medical Center Learning Objectives Identify
More informationInherited Breast and Ovarian Cancer: 20 Years of Progress and Future Directions
Inherited Breast and Ovarian Cancer: 20 Years of Progress and Future Directions Noah D. Kauff, MD, FACOG Director, Clinical Cancer Genetics Duke Cancer Institute / Duke University Health System Disclosures
More information6/8/17. Genetics 101. Professor, College of Medicine. President & Chief Medical Officer. Hereditary Breast and Ovarian Cancer 2017
Genetics 101 Hereditary Breast and Ovarian Cancer 2017 Rebecca Sutphen, MD, FACMG Professor, College of Medicine President & Chief Medical Officer INVASIVE CANCER GENETICALLY ALTERED CELL HYPERPLASIA DYSPLASIA
More informationBiology Response Controversies and Advances
Biology Response Controversies and Advances in BRCA related ovarian cancer Lessons learned and future directions Michael Friedlander The Prince of Wales Hospital and Royal Hospital for Women Sydney BREAST-CANCER
More informationManagement of BRCA Positive Breast Cancer. Archana Ganaraj, MD February 17, 2018 UPDATE ON WOMEN S HEALTH
Management of BRCA Positive Breast Cancer Archana Ganaraj, MD February 17, 2018 UPDATE ON WOMEN S HEALTH The number of American women who have lost their lives to breast cancer outstrips the total number
More informationCarrier Frequency. Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations. Olivia Pagani On behalf of Bella Kaufman
Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations Olivia Pagani On behalf of Bella Kaufman Carrier Frequency Prevalence of an altered disease gene in a given population 1 Background
More informationBreast Cancer and Treatment Options in Patients with BRCA1/2 mutations. Olivia Pagani On behalf of Bella Kaufman
Breast Cancer and Treatment Options in Patients with BRCA1/2 mutations Olivia Pagani On behalf of Bella Kaufman Carrier Frequency Prevalence of an altered disease gene in a given population Background
More informationRisk Assessment, Genetics, and Prevention
Risk Assessment, Genetics, and Prevention Katherine D. Crew, MD MS Director, Clinical Breast Cancer Prevention Program Columbia University Medical Center 1 Outline Breast cancer risk factors Hereditary
More informationProphylactic Mastectomy State of the Art
Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065 6 th Brazilian Breast Cancer Conference Sao Paulo, Brazil 9 March 2012 Prophylactic Mastectomy State of the Art Monica Morrow
More informationRisk-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
More informationPolicy Specific Section: Medical Necessity and Investigational / Experimental. October 15, 1997 October 9, 2013
Medical Policy Genetic Testing for Hereditary Breast and/or Ovarian Cancer Type: Medical Necessity and Investigational / Experimental Policy Specific Section: Laboratory/Pathology Original Policy Date:
More informationVirtual Journal Club. Ovarian Cancer. Reference Slides. Platinum-Sensitive Recurrent Ovarian Cancer: Making the Most of Emerging Targeted Therapies
Virtual Journal Club Ovarian Cancer Reference Slides Platinum-Sensitive Recurrent Ovarian Cancer: Making the Most of Emerging Targeted Therapies Mansoor R. Mirza, MD Copenhagen University Hospital Rigshospitalet
More informationObjectives. Case Study #1 1/28/14. A Collaborative Practice Approach to Genetic Testing in Cancer: Translating Science Into Clinical Practice
A Collaborative Practice Approach to Genetic Testing in Cancer: Translating Science Into Clinical Practice Heather Hampel, MS, CGC Associate Director, Division of Human Genetics Professor, Department of
More informationPrimary Care Approach to Genetic Cancer Syndromes
Primary Care Approach to Genetic Cancer Syndromes Jason M. Goldman, MD, FACP FAU School of Medicine Syndromes Hereditary Breast and Ovarian Cancer (HBOC) Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
More informationGenetic Panel Testing and Implications for Cancer Care
Genetic Panel Testing and Implications for Cancer Care Dana Zakalik, M.D. Nancy and James Grosfeld Cancer Genetics Center Professor, OUWB Medical School MCC Board of Directors Meeting September 28, 2016
More informationIdentification of patients suggestive of hereditary breast and ovarian cancer syndrome that warrants further professional evaluation.
Allina Breast Program Committee Consensus Guidelines These guidelines apply to clinical interventions that have well-documented outcomes, but whose outcomes are not clearly desirable to all patients Identification
More informationPARP inhibitors for breast cancer
PARP inhibitors for breast cancer Mark Robson, MD Memorial Sloan Kettering Cancer Center Agenda Mechanism of action Clinical studies Resistance mechanisms Future directions Poly (ADP-ribose) Polymerases
More informationReference #: SYS-PC-VPCI-CG-002. Origination Date: June 2012 Next Review Date: April 2019 Effective Date: April 2016
Oncology Service Line-Allina Health System-wide Consensus Guidelines: Identification of Breast Cancer Patients at Risk for Inherited Cancer Risks These guidelines apply to clinical interventions that have
More informationMedical Policy Manual. Topic: Genetic Testing for Hereditary Breast and/or Ovarian Cancer. Date of Origin: January 27, 2011
Medical Policy Manual Topic: Genetic Testing for Hereditary Breast and/or Ovarian Cancer Date of Origin: January 27, 2011 Section: Genetic Testing Last Reviewed Date: July 2014 Policy No: 02 Effective
More informationBreast Cancer Risk Assessment: Genetics, Risk Models, and Screening. Amie Hass, MSN, ARNP, FNP-BC Hall-Perrine Cancer Center
Breast Cancer Risk Assessment: Genetics, Risk Models, and Screening Amie Hass, MSN, ARNP, FNP-BC Hall-Perrine Cancer Center Disclosure- I DO NOT HAVE any relevant financial interest with any entity producing,
More informationCorporate Medical Policy
Corporate Medical Policy Moderate Penetrance Variants Associated with Breast Cancer in File Name: Origination: Last CAP Review: Next CAP Review: Last Review: moderate_penetrance_variants_associated_with_breast_cancer_
More informationBreast MRI: Friend or Foe?
Breast MRI: Friend or Foe? UCSF Postgraduate Course May 18, 2013 Cheryl Ewing, MD Clinical Professor of Surgery UCSF Department of Surgery APPLEGATE HAS DOUBLE MASTECTOMY IN CANCER SCARE DIAGNOSED WITH
More informationBRCA1 & BRCA2: CANCER RISK & GENETIC TESTING IAP ID 2013 NAIR HOSPITAL, MUMBAI
BRCA1 & BRCA2: CANCER RISK & GENETIC TESTING IAP ID 2013 NAIR HOSPITAL, MUMBAI DR KIRTI CHADHA MD (Path), PDCC (Oncopath & Oncohemat) CONSULTANT SURGICAL PATHOLOGIST NATIONAL COORDINATOR,SURGICAL PATHOLOGY
More informationAssessment and Management of Genetic Predisposition to Breast Cancer. Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18
Assessment and Management of Genetic Predisposition to Breast Cancer Dr Munaza Ahmed Consultant Clinical Geneticist 2/7/18 Overview The role of the Cancer Genetics team NICE guidelines for Familial Breast
More informationManagement of BRCA mutation carriers
Management of BRCA mutation carriers Clinical Case Presentation Shani Paluch-Shimon, MBBS, MSc Head, Breast Cancer Service for Young Women Oncology Institute Sheba Medical Center, Israel esmo.org DISCLOSURES
More informationBRCA Precertification Information Request Form
BRCA Precertification Information Request Form Failure to complete this form in its entirety may result in the delay of review. Fax to: BRCA Precertification Department Fax number: 1-860-975-9126 Section
More informationHereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2
GENETEST REVIEW Genetics in Medicine Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2 Nancie Petrucelli, MS, CGC 1, Mary B. Daly, MD, PhD 2, and Gerald L. Feldman, MD, PhD 3 TABLE
More informationKey Recommendations. Gynecologic management of women with inherited risk of gynecologic cancer
Gynecologic management of women with inherited risk of gynecologic cancer C. Bethan Powell MD Kaiser Permanente Northern California Gynecologic Oncology Program Lead, Kaiser Permanente Northern California
More informationOBJECTIVES 8/25/2017. An attempt to organize the chaos
High Risk for Breast Cancer and Genetics: Who? What? Where? When? An attempt to organize the chaos Presented at Winds of Change Conference November 3, 2017 by Carol Hager, MSN, CRNP and Allison Haener,
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(adp-ribose)
More informationBreast Cancer Statistics
1 in 8 Breast Cancer Statistics Incidence Mortality Prevalence 2 Breast Cancer Incidence Breast Cancer Mortality Breast Cancer Prevalence ~$100,000 Female Breast Anatomy Breasts consist mainly of fatty
More informationCorporate Medical Policy Genetic Testing for Breast and Ovarian Cancer
Corporate Medical Policy Genetic Testing for Breast and Ovarian Cancer File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_breast_and_ovarian_cancer 8/1997 8/2017
More informationBRCA mutation carrier patient: How to manage?
BRCA mutation carrier patient: How to manage? Clinical Case Presentation Katarzyna Sosińska-Mielcarek Department of Oncology and Radiotherapy University Clinical Center Gdansk, Poland esmo.org DISCLOSURE
More informationDoes Cancer Run in Your Family?
Does Cancer Run in Your Family? Nancie Petrucelli, MS, CGC Clinical Assistant Professor Certified Genetic Counselor/Coordinator Cancer Genetic Counseling Service Karmanos Cancer Institute Wayne State University
More informationHereditary Breast and Ovarian Cancer and Genetic Cancer Risk Assessment (GCRA)
Hereditary Breast and Ovarian Cancer and Genetic Cancer Risk Assessment (GCRA) UPR CCC 04/12/13 Jeffrey N. Weitzel, M.D. Risks Related to Breast Cancer Advancing Age Early Menarche Lack of Exercise Alcohol
More informationOverview and future horizons of PARP inhibitors in BRCAassociated. Judith Balmaña
Overview and future horizons of PARP inhibitors in BRCAassociated breast cancer Judith Balmaña PARP inhibitors: Mechanism of action Clinical development: Monotherapy In combination with chemotherapy Ongoing
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
BRCA1 and BRCA2 Testing Page 1 of 33 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: BRCA1 and BRCA2 Testing Pre-Determination of Services IS REQUIRED by the Member
More informationTargeting DNA repair in BRCA 1/2 and Triple Negative Breast Cancer
Targeting DNA repair in BRCA 1/2 and Triple Negative Breast Cancer Andrew Tutt, MB ChB, PhD Consultant Oncologist/Director Breakthrough Breast Cancer Research Unit King s Health Partners Academic Health
More informationMP Genetic Testing for BRCA1 or BRCA2 for Hereditary Breast/Ovarian Cancer Syndrome and Other High-Risk Cancers
Medical Policy MP 2.04.02 Genetic Testing for BRCA1 or BRCA2 for Hereditary Breast/Ovarian Cancer Syndrome and Other High-Risk BCBSA Ref. Policy: 2.04.02 Last Review: 11/15/2018 Effective Date: 02/15/2019
More informationSo, now, that we have reviewed some basics of cancer genetics I will provide an overview of some common syndromes.
Hello. My name is Maureen Mork and I m a Certified Genetic Counselor in the Clinical Cancer Genetics Program at The University of Texas MD Anderson Cancer Center. I ll be lecturing today on the Cancer
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
BRCA1 and BRCA2 Testing Page 1 of 26 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: BRCA1 and BRCA2 Testing Pre-Determination of Services IS REQUIRED by the Member
More informationThe impact of hereditary breast and ovarian cancer (HBOC) syndrome testing on patient management and your practice
The impact of hereditary breast and ovarian cancer (HBOC) syndrome testing on patient management and your practice Use BRACAnalysis as a guide in your medical and surgical management BRACAnalysis testing
More informationDoes Cancer Run in Your Family?
Does Cancer Run in Your Family? A Patient s Guide to Hereditary Breast and Ovarian Cancer Syndrome What is Hereditary Cancer? Most cancers occur in people who do not have a strong family history of that
More informationGenetic Testing: who, what, why?
Genetic Testing: who, what, why? Gina Westhoff MD LMG Gynecologic Oncology March 16, 2019 Disclosures Speaker for Merck (unrelated to today s topic) Objectives Determine who should undergo genetic risk
More informationPARP Inhibitors: Patients Selection. Dr. Cristina Martin Lorente Hospital de la Santa Creu i Sant Pau Formigal, June 23th 2016
PARP Inhibitors: Patients Selection Dr. Cristina Martin Lorente Hospital de la Santa Creu i Sant Pau Formigal, June 23th 2016 OVARIAN CANCER (OC): MULTIPLES DISEASES Different types with different behaviour
More informationGenetic Testing for BRCA1 and BRCA2 Genes
Genetic Testing for BRCA1 and BRCA2 Genes MP9478 Covered Service: Prior Authorization Required: Additional Information: Yes when meets criteria below Yes as shown below Pre and post-test genetic counseling
More informationGenetic counseling and testing. Shani Paluch-Shimon, MBBS, MSc Director, Breast Oncology Unit Shaare Zedek Medical Centre, Jerusalem Israel
Genetic counseling and testing Shani Paluch-Shimon, MBBS, MSc Director, Breast Oncology Unit Shaare Zedek Medical Centre, Jerusalem Israel Disclosures Roche: Speakers bureau, honoraria, consultancy Astra
More informationOutline. Identifying your risk for hereditary breast or ovarian cancer. Genetics 101. What causes cancer? Genetics
Identifying your risk for hereditary breast or ovarian cancer David Andorsky, MD Breanna Roscow, MS, CGC 303-993-0161 Outline Genetics and biology of hereditary cancer syndromes BRCA1 and BRCA2 Genetic
More informationDieta Brandsma, Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
What is hot in breast cancer brain metastases? Dieta Brandsma, Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands 8th Annual Brain Metastases Research and Emerging Therapy
More informationApproximately 5% to 10% of breast cancer (BC) is hereditary in nature. Since. By Dawna Gilchrist, MD, FRCPC, FCCMG
By Dawna Gilchrist, MD, FRCPC, FCCMG Approximately 5% to 10% of breast cancer (BC) is hereditary in nature. Since the discovery of the genes BRCA 1 and 2 in the early 1990s, genetic counselling and testing
More informationBRCAplus. genetic testing for hereditary breast cancer
BRCAplus genetic testing for hereditary breast cancer Developed in collaboration with Fox Chase Cancer Center and the Arcadia University Genetic Counseling Program. Causes of Hereditary Breast Cancer familial
More informationCancer Genomics 101. BCCCP 2015 Annual Meeting
Cancer Genomics 101 BCCCP 2015 Annual Meeting Objectives Identify red flags in a person s personal and family medical history that indicate a potential inherited susceptibility to cancer Develop a systematic
More informationProphylactic Mastectomy
Prophylactic Mastectomy Policy Number: Original Effective Date: MM.06.010 01/01/2009 Line(s) of Business: Current Effective Date: HMO; PPO 08/24/2012 Section: Surgery Place(s) of Service: Inpatient I.
More informationPROVIDER POLICIES & PROCEDURES
PROVIDER POLICIES & PROCEDURES BRCA GENETIC TESTING The purpose of this document is to assist providers enrolled in the Connecticut Medical Assistance Program (CMAP) with the information needed to support
More informationOverview of peculiarities and therapeutic options for patients with breast cancer and a BRCA germline mutation
Overview of peculiarities and therapeutic options for patients with breast cancer and a BRCA germline mutation Dr Niklas Loman PhD MD Consultant oncologist Skåne University Hospital Lund, Suecia Prognosis
More informationGenetic Testing for BRCA1 and BRCA2 Genes
Genetic Testing f BRCA1 and BRCA2 Genes MP9478 Covered Service: Pri Authization Required: Additional Infmation: Yes when meets criteria below Yes--as shown below Pre and post-test genetic counseling is
More informationWHAT DO GENES HAVE TO DO WITH IT? Breast Cancer Risk Assessment and Risk Reduction in 2016
WHAT DO GENES HAVE TO DO WITH IT? Breast Cancer Risk Assessment and Risk Reduction in 2016 39 th Annual CANP Educational Conference March 17 20, 2016 Collaborate. Educate. Advocate. Karen Herold, DNP,
More informationPrevalence and clinical implications of BRCA1/2 germline mutations in Chinese women with breast cancer Yuntao Xie M.D., Ph.D.
Prevalence and clinical implications of BRCA1/2 germline mutations in Chinese women with breast cancer Yuntao Xie M.D., Ph.D. Hereditary Cancer Center, Peking University Cancer Hospital 1 Breast cancer
More informationFactors Associated with Early Versus Late Development of Breast and Ovarian Cancer in BRCA1 and BRCA2 Positive Women
Texas Medical Center Library DigitalCommons@The Texas Medical Center UT GSBS Dissertations and Theses (Open Access) Graduate School of Biomedical Sciences 5-2010 Factors Associated with Early Versus Late
More informationAssessing Your Patient s Breast Cancer Risk: Is Genetic Testing Necessary?
May 16, 2016 Assessing Your Patient s Breast Cancer Risk: Is Genetic Testing Necessary? Presenter: Emily Kuchinsky, MS, CGC 1 Experiences with Genetic Testing Adverse Events in Cancer Genetic Testing:
More information2/21/2016. Cancer Precision Medicine: A Primer. Ovarian Cancer Statistics and Standard of Care in 2015 OUTLINE. Background
Cancer Precision Medicine: A Primer Rebecca C. Arend, MD Division of Gyn Oncology OUTLINE Background Where we are Where we have been Where we are going Targeted Therapy in Ovarian Cancer How to Individualized
More informationGermline Testing for Hereditary Cancer with Multigene Panel
Germline Testing for Hereditary Cancer with Multigene Panel Po-Han Lin, MD Department of Medical Genetics National Taiwan University Hospital 2017-04-20 Disclosure No relevant financial relationships with
More informationBrian T Burgess, DO, PhD, GYN Oncology Fellow Rachel W. Miller, MD, GYN Oncology
Brian T Burgess, DO, PhD, GYN Oncology Fellow Rachel W. Miller, MD, GYN Oncology Epithelial Ovarian Cancer - Standard Current Treatment: Surgery with De-bulking + Platinum-Taxane based Chemotherapy - No
More informationCarol Christianson, MS, CGC Genetic Counselor West Michigan Cancer Center
Carol Christianson, MS, CGC Genetic Counselor West Michigan Cancer Center Following this presentation you will be able to: Identify cancer survivors in your practice who might benefit from genetic counseling
More informationImportance of Family History in Gynecologic Cancer Prevention. Objectives. Genetic Counselors. Angela Thompson, MS, CGC
Importance of Family History in Gynecologic Cancer Prevention Angela Thompson, MS, CGC Genetic Counselor Froedtert & The Medical College of Wisconsin Objectives Introduce role of genetic counselor Discuss
More informationBSO, HRT, and ERT. No relevant financial disclosures
BSO, HRT, and ERT Jubilee Brown, MD Professor & Associate Director, Gynecologic Oncology Levine Cancer Institute at the Carolinas HealthCare System Charlotte, North Carolina No relevant financial disclosures
More informationGENETIC MANAGEMENT OF A FAMILY HISTORY OF BREAST AND / OR OVARIAN CANCER. Dr Abhijit Dixit. Family Health Clinical Genetics
GENETIC MANAGEMENT OF A FAMILY HISTORY OF BREAST AND / OR OVARIAN CANCER Full Title of Guideline: Author (include email and role): Division & Speciality: Scope (Target audience, state if Trust wide): Review
More informationRole of genetic testing in familial breast cancer outside of BRCA1 and BRCA2
Role of genetic testing in familial breast cancer outside of BRCA1 and BRCA2 Introduction Most commonly diagnosed cancer in South African women and the second most commonly diagnosed cancer in Black women
More informationJ Clin Oncol 22: by American Society of Clinical Oncology INTRODUCTION. Women who carry a germline mutation in
VOLUME 22 NUMBER 12 JUNE 15 2004 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers Kelly Metcalfe, Henry T. Lynch, Parviz Ghadirian,
More informationGEN ETICS AN D GEN OM ICS IN CANCER PREVENTION AN D TREATM EN T. Robert Nathan Slotnick MD PhD Director, Medical Genetics and Genomics
GEN ETICS AN D GEN OM ICS IN CANCER PREVENTION AN D TREATM EN T Robert Nathan Slotnick MD PhD Director, Medical Genetics and Genomics The Medical/Surgical/Radiation Oncologist s View of Genetics Cancer
More informationCANCER GENETICS PROVIDER SURVEY
Dear Participant, Previously you agreed to participate in an evaluation of an education program we developed for primary care providers on the topic of cancer genetics. This is an IRB-approved, CDCfunded
More informationGynecologic Cancers are many diseases. Gynecologic Cancers in the Age of Precision Medicine Advances in Internal Medicine. Speaker Disclosure:
Gynecologic Cancer Care in the Age of Precision Medicine Gynecologic Cancers in the Age of Precision Medicine Advances in Internal Medicine Lee-may Chen, MD Department of Obstetrics, Gynecology & Reproductive
More information1. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45
1 2 3 1. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women
More informationGynecologic Cancers are many diseases. Speaker Disclosure: Gynecologic Cancer Care in the Age of Precision Medicine. Controversies in Women s Health
Gynecologic Cancer Care in the Age of Precision Medicine Gynecologic Cancers in the Age of Precision Medicine Controversies in Women s Health Lee-may Chen, MD Department of Obstetrics, Gynecology & Reproductive
More informationMANAGEMENT OF HIGH RISK BREAST PATIENTS DR PAMELA THOMPSON BREAST PHYSICIAN, FSH
MANAGEMENT OF HIGH RISK BREAST PATIENTS DR PAMELA THOMPSON BREAST PHYSICIAN, FSH HIGH RISK MANAGEMENT OBJECTIVES Be alert to FHx Breast and/or Ovarian cancer Know how to perform a risk assessment Be aware
More informationNon-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document.
MRI OF THE BREAST Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs
More informationBRCA 1/2. Breast cancer testing THINK ABOUT TOMORROW, TODAY
BRCA 1/2 Breast cancer testing THINK ABOUT TOMORROW, TODAY 5 10% of patients with breast and/or ovarian cancer have a hereditary form1. For any individual carrying a mutation in BRCA1 or BRCA2, the lifetime
More informationModerate Penetrance Variants Associated With Breast Cancer in Individuals at High Breast Cancer Risk
Moderate Penetrance Variants Associated With Breast Cancer in Individuals at High Breast Cancer Risk Policy Number: 2.04.126 Last Review: 3/2018 Origination: 3/2017 Next Review: 3/2019 Policy Blue Cross
More informationHereditary breast cancer who to refer to a cancer genetics clinic and how to counsel patients with
Hereditary breast cancer who to refer to a cancer genetics clinic and how to counsel patients with positive and negative results? SAMO Workshop Luzern 3./4.10.2014 Dr. med. Barbara Bolliger TumorTumor-
More informationFAQ-Protocol 3. BRCA mutation carrier guidelines Frequently asked questions
ULast updated: 09/02/2015 Protocol 3 BRCA mutation carrier guidelines Frequently asked questions UQ: How accurate are the remaining lifetime and 5 year breast cancer risks in the table? These figures are
More informationSo, Who are the appropriate individuals that should consider genetic counseling and genetic testing?
Hello, I m Banu Arun, Professor of Breast Medical Oncology and Co-Director of Clinical Cancer Genetics at the University of Texas MD Anderson Cancer Center. Today I will be discussing with you Hereditary
More informationApplies to: All Aetna plans, except Traditional Choice plans. All Innovation Health plans, except indemnity plans
BRCA Precertification Information Request Form Applies to: All Aetna plans, except Traditional Choice plans All Innovation Health plans, except indemnity plans All Health benefits and health insurance
More informationModelling cancer risk predictions:clinical practice perspective.
Modelling cancer risk predictions:clinical practice perspective. Judith Balmaña, MD, PhD Familial Cancer Program Medical Oncology Department Hospital Vall d Hebron, VHIO Barcelona, Spain It is very difficult
More informationGENETIC TESTING FOR HEREDITARY BREAST AND OVARIAN CANCER BRCA1 BRCA2
GENETIC TESTING FOR HEREDITARY BREAST AND OVARIAN CANCER BRCA1 BRCA2 Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific
More informationObjectives: Describe poly-adp-ribose polymerase (PARP) inhibitors mechanism of action.
1 2 3 Role of PARP Inhibitors in Metastatic Breast Cancer Catie Chatowsky, PharmD PGY1 Pharmacy Resident Disclosure: I have nothing to disclose. Objectives: Describe poly-adp-ribose polymerase (PARP) inhibitors
More informationInhibidores de PARP Una realidad? dónde y cuando?
Inhibidores de PARP Una realidad? dónde y cuando? Alberto Ocana Hospital Universitario Albacete Centro Regional Investigaciones Biomédicas CIC-Salamanca DNA repair mechanisms DNA is continually exposed
More informationGENETIC TESTING FOR HEREDITARY BREAST AND OVARIAN CANCER SYNDROME BRCA1 BRCA2
SYNDROME BRCA1 BRCA2 Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs
More informationThe best way of detection of and screening for breast cancer in women with genetic or hereditary risk
The best way of detection of and screening for breast cancer in women with genetic or hereditary risk Ingrid Vogelaar Introduction Each year almost 1.2 million women are diagnosed with breast cancer worldwide.
More informationHost Factors that Increase Breast Cancer Risk
Host Factors that Increase Breast Cancer Risk 30 th Annual Miami Breast Cancer Conference March 7-10, 2013 Debu Tripathy, MD Professor of Medicine University of Southern California Norris Comprehensive
More informationBRCA Testing in Ovarian cancer Arabic Approach
BRCA Testing in Ovarian cancer Arabic Approach Khalid El Khalfaoui Departement of Gynecology and Gyn Oncology Wermelskirchen Hospital 25.04.2018 Krankenhaus Wermelskirchen GmbH I 1 Development of cancer
More information