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NCCN: Genetic/Familial High-Risk Assessment: Breast and Ovarian NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Genetic/Familial High-Risk Assessment: Breast and Ovarian Version 3.2019 — January 18, 2019 NCCN.org Continue Version 3.2019, 01/18/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 3.2019 Table of Contents Genetic/Familial High-Risk Assessment: Breast and Ovarian Discussion *Mary B. Daly, MD, PhD/Chair † Catherine Klein, MD † Þ Holly J. Pederson, MD Fox Chase Cancer Center University of Colorado Cancer Center Case Comprehensive Cancer Center/ University Hospitals Seidman Cancer Center *Robert Pilarski, MS, CGC/Vice-chair ∆ Wendy Kohlmann, MS, CGC ∆ and Cleveland Clinic Taussig Cancer Institute The Ohio State University Comprehensive Huntsman Cancer Institute Cancer Center - James Cancer Hospital at the University of Utah Gwen Reiser, MS, CGC ∆ and Solove Research Institute Fred & Pamela Buffett Cancer Center Allison W. Kurian, MD, MSc † Þ ∆ Michael P. Berry, MD ¶ Stanford Cancer Institute Kristen Mahoney Shannon, MS, CGC † ∆ St. Jude Children’s Research Hospital/ Massachusetts General Hospital The University of Tennessee Health Christine Laronga, MD ¶ Cancer Center Science Center Moffitt Cancer Center Premal Thaker, MD Ω Saundra S. Buys, MD ‡ Þ † Jennifer K. Litton, MD † Siteman Cancer Center at Barnes- Huntsman Cancer Institute The University of Texas Jewish Hospital and Washington at the University of Utah MD Anderson Cancer Center University School of Medicine Susan Friedman, DVM ¥ Lisa Madlensky, PhD, CGC ∆ Kala Visvanathan, MD, MHS † Þ FORCE: Facing Our Risk of Cancer UC San Diego Moores Cancer Center The Sidney Kimmel Comprehensive Empowered Cancer Center at Johns Hopkins Julie S. Mak, MS, MSc, CGC ∆ Judy E. Garber, MD, MPH † UCSF Helen Diller Family Jeffrey N. Weitzel, MD † ‡ ∆ Dana-Farber/Brigham and Comprehensive Cancer Center City of Hope Comprehensive Cancer Center Women’s Cancer Center Sofia D. Merajver, MD, PhD ‡ Þ Myra J. Wick, MD, PhD Ω ∆ Mollie L. Hutton, MS, CGC ∆ University of Michigan Mayo Clinic Cancer Center Roswell Park Cancer Institute Rogel Cancer Center Kari B. Wisinski, MD † Noah D. Kauff, MD ∆ Ω Kenneth Offit, MD † Þ ∆ University of Wisconsin Duke Cancer Institute Memorial Sloan Kettering Cancer Center Carbone Cancer Center Seema Khan, MD ¶ Tuya Pal, MD ∆ NCCN Robert H. Lurie Comprehensive Cancer Vanderbilt-Ingram Cancer Center Susan Darlow, PhD Center of Northwestern University Mary Dwyer, MS † Medical oncology ∆ Cancer/Medical genetics Þ Internal medicine ‡ Hematology/Hematology oncology Ω Gynecologic oncology/Gynecology NCCN Guidelines Panel Disclosures Continue ¶ Breast surgical oncology & Public health and preventive medicine ¥ Patient advocacy *Discussion Writing Committee Member Version 3.2019, 01/18/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 3.2019 Table of Contents Genetic/Familial High-Risk Assessment: Breast and Ovarian Discussion NCCN Genetic/Familial High-Risk Assessment Panel Members Clinical Trials: NCCN believes that Summary of the Guidelines Updates the best management for any patient with cancer is in a clinical trial. Breast and/or Ovarian Cancer Genetic Assessment (BR/OV-1) Participation in clinical trials is especially encouraged. BRCA-Related Breast and/or Ovarian Cancer Syndrome (BRCA-1) To find clinical trials online at NCCN Member Institutions, click here: BRCA Mutation-Positive Management (BRCA-A) nccn.org/clinical_trials/clinicians.aspx. NCCN Categories of Evidence and Li-Fraumeni Syndrome (LIFR-1) Consensus: All recommendations Li-Fraumeni Syndrome Management in Adults (LIFR-A) are category 2A unless otherwise indicated. Cowden Syndrome/PTEN Hamartoma Tumor Syndrome (COWD-1) See NCCN Categories of Evidence Cowden Syndrome/PHTS Management (COWD-A) and Consensus. Multi-Gene Testing (GENE-1) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2019. Version 3.2019, 01/18/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 3.2019 Table of Contents Genetic/Familial High-Risk Assessment: Breast and Ovarian Discussion Updates in Version 3.2019 of the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian from Version 2.2019 include: MS-1 • The Discussion section has been updated to reflect the changes in the algorithm. Updates in Version 2.2019 of the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian from Version 1.2019 include: BRCA-Related Breast and/or Ovarian Cancer Syndrome BRCA-1 • BRCA1/2 Testing Criteria Under the 2nd bullet, Personal history of breast cancer + one or more of the following: ◊ The 1st sub-bullet was revised as, “Diagnosed ≤50 46-50 y with:” – The 3rd tertiary bullet was added, “≥1 close blood relative with high-grade (Gleason score ≥7) prostate cancer” ◊ Under the 4th sub-bullet, Diagnosed at any age with ≥1 close blood relative with: – The criterion was revised by removing, “high-grade (Gleason score ≥7) or” from “metastatic prostate cancer” Updates in Version 1.2019 of the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian from Version 1.2018 include: Global BR/OV-A 2 of 3 • "Mutation" was changed to "pathogenic/likely pathogenic variant" • Genetic Testing Approach throughout the guidelines. 3rd bullet, 1st sentence was revised, "If no pathogenic/likely pathogenic variant is found, consider referral for expert genetics evaluation if not Breast and Ovarian Cancer Genetic Assessment yet performed; testing for other hereditary cancer syndromes may be BR/OV-1 appropriate other hereditary cancer syndromes." • Criteria for Further Genetic Risk Evaluation BR/OV-A 3 of 3 The criteria were extensively revised and reorganized. • A new section titled, "Evaluating the Source of Genetic Testing Information" • The following footnotes were added: was added. Footnote b, "Irrespective of degree of relatedness." BRCA-Related Breast and/or Ovarian Cancer Syndrome Footnote d, "Metastatic prostate cancer is biopsy-proven and/or with BRCA-1 radiographic evidence and includes distant metastasis and regional bed or nodes. It is not a biochemical recurrence." • BRCA1/2 Testing Criteria Footnote g, "When possible, genetic testing should be performed first on The criteria were extensively revised and reorganized. an affected family member." • The following footnotes were added: The following footnotes were removed: Footnote b, "Irrespective of degree of relatedness." ◊ "For populations at increased risk due to founder mutations, Footnote i, "Approximately 2%–5% of unselected cases of pancreatic requirements for inclusion may be modified." adenocarcinoma will have a BRCA1/2 pathogenic/likely pathogenic ◊ "For lobular breast cancer with a family history of diffuse gastric variant. However, the disease is highly lethal and the option to test the cancer, CDH1 gene testing should be considered." affected relative may not be available in the future ... (Holter S, Borgida ◊ "For hamartomatous colon polyps in conjunction with breast cancer A, Dodd A, et al. J Clin Oncol 2015;33:3124-3129. Shindo K, Yu J, and hyperpigmented macules of the lips and oral mucosa, STK11 Suenaga M, et al. J Clin Oncol 2017;35:3382-3390.)" testing should be considered. See NCCN Guidelines for Genetic/ Footnote j, "Eg, PARP inhibitors for ovarian cancer and metastatic Familial High-Risk Assessment: Colorectal–Peutz-Jeghers syndrome. Melanoma has been reported in some BRCA-related families." HER2-negative breast cancer; platinum therapy for prostate cancer. See the relevant NCCN treatment guidelines (eg, NCCN Guidelines for Breast BR/OV-A 1 of 3 Cancer; NCCN Guidelines for Prostate Cancer) for further details." • Genetic Testing Considerations Footnote k, "This may be extended to an affected third-degree relative if 4th bullet, 2nd sentence was added, “It is encouraged that testing be related through two male relatives (eg, paternal grandfather’s mother or done in commercial or academic labs that are clinically approved and sister.)" Continued validated." Version 3.2019, 01/18/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. UPDATES NCCN Guidelines Index NCCN Guidelines Version 3.2019 Table of
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