Download Free Medical Hereditary Cancer Syndromes PowerPoint Presentation

Hereditary Cancer Syndromes PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Cowden Syndrome, which is titled "Hereditary Cancer Syndromes", to know about the patterns of hereditary cancer syndromes and identify appropriate patients for referral, the rationale of multi-gene panel testing and review fundamentals of pre-test and post-test counseling, and basic management of patients with hereditary cancer syndromes.

Tags : Cowden Syndrome, Hereditary Cancer Syndromes, multi-gene panel testing

Published on : May 13, 2021 | Views : 2569 | Downloads : 7

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Elizabeth Kent MD Medical Oncology/Hematology Hereditary Cancer Syndromes Recognition, Testing and Management
Slide 2-

Disclosures Nothing to disclose
Slide 3-

Objectives Recognize patterns of hereditary cancer syndromes and identify appropriate patients for referral Discuss the rationale of multi-gene panel testing and review fundamentals of pre-test and post-test counseling Review basic management of patients with hereditary cancer syndromes
Slide 4-

Hereditary Cancer Syndrome basics <10% of common cancers are hereditary 5-8%
Slide 5-

Hereditary Cancer Syndrome basics >50 hereditary cancer syndromes described Typically mutations in tumor suppressors genes or DNA repair genes/mismatch repair genes Most autosomal dominant Incomplete penetrance
Slide 6-

Hereditary Cancer Syndromes “Common” BRCA 1/2 – 5-8% of breast cancer Lynch syndrome (HNPCC) – 2-3% of CRC Less common Li-Fraumeni – p53 mutation FAP – familial adenomatous polyposis Attenuated FAP MUTYH Cowden’s syndrome Multiple endocrine neoplasia (MEN) syndromes Hereditary diffuse gastric cancer
Slide 7-

Hereditary Cancer Syndromes
Slide 8-

BRCA 1 and 2 Responsible for 5-8% of all breast cancer DNA repair genes Lifetime risks Breast cancer – up to 80% Ovarian cancer – up to 45% Male breast cancer – 8% Prostate cancer –20% Pancreatic cancer – 7%
Slide 9-

BRCA 1 and 2 BRCA 1 Early age onset Higher b/o cancer risks Breast 85% Ovarian 45% Higher triple negative BRCA 2 Average age onset Lower b/o risks Breast 60% Ovarian 15% Higher risk high grade prostate cancer Increased risk melanoma
Slide 10-

BRCA 1/2 NCCN guidelines Family member with known mutation Breast cancer ≤45y Breast cancer ≤50y with 2 primary breast cancers ≥1 relative with breast cancer ≥1 relative with pancreatic ca ≥1 relative with prostate cancer Unknown/limited FHx ≤60yo with triple negative Any age ≥2 relatives with breast, panc or prost ≥1 relative ovarian cancer ≥1 relative breast cancer<50 Relative with male breast cancer Ashkenazi Jewish ancestry Male breast cancer Ovarian cancer Prostate cancer with ≥1 relative ovarian cancer ≥1 relative breast cancer<50 2 relatives with breast, panc, prost Pancreatic cancer with ≥1 relative ovarian cancer ≥1 relative breast cancer<50 2 relatives with breast, panc, prost Ashkenazi Jewish ancestry Family history only First or second degree relative meeting any of the above criteria Third degree relative with breast/ovarian cancer + ≥2 relatives with breast, panc or prost
Slide 11-

BRCA 1/2 Recommendations for carriers Surveillance Annual breast MRI starting at 25yo Annual mammogram starting at 30yo TVUS and CA125 starting at 30yo* Prophylaxis Pharmacologic Breast – SERM, AI Ovarian – OCP Surgical Bilateral mastectomy RRSO – risk reducing salpingo-oophorectomy Age 35-40 BRCA1, age 40-45 BRCA 2
Slide 12-

Lynch syndrome Hereditary non-polyposis colorectal cancer (HNPCC) Mismatch repair genes MLH1, MSH2, MSH6, PMS2, EPCAM Lifetime risks Colorectal cancer – 80%; adenomatous polyps 90% Uterine cancer – 70% Ovarian cancer – 10% Urothelial cancers – 20% Gastric, breast, small bowel, biliary, brain, sebaceous gland
Slide 13-

Lynch syndrome Most onset <50yo Tumors are typically: Absent mismatch repair on IHC Microsatellite instability (MSI) - high
Slide 14-

Lynch syndrome Classic Amsterdam criteria (3-2-1-0) 3 affected, 2 generations, 1<50yo, 0 FAP Revised Bethesda criteria CRC<50yo 2 or more LS related tumors CRC with MSI-H in <60yo CRC with 1 relative with LS related ca <50 CRC with 2 relatives with LS related ca any age
Slide 15-

Lynch Syndrome management Surveillance Annual colonoscopy at 20yo TVUS and CA125 q6m* Annual endometrial sampling* Consider EGD q3-5y starting at 30yo Consider annual urinalysis at 25 Prophylaxis ASA? Prophylactic TAH-BSO after childbearing Total abdominal colectomy with ileorectal anastomosis with endorectal scope annually
Slide 16-

FAP/attenuated FAP FAP >100 polyps Virtually 100% lifetime risk of CRC by age 45yo Extracolonic Duodenal adenomas Desmoid tumors Papillary thyroid ca Management Total colectomy with IRA Annual EGD aFAP 10-100 polyps Up to 80% risk CRC Average age 56y Similar extracolonic risks Management Annual colonoscopy at 20yo Total colectomy with IRA depending on polyp burden Annual EGD
Slide 17-

MUTYH Autosomal recessive 10-100 lifetime polyps Lifetime risk of CRC is up to 75% Annual colonoscopy starting at 25yo
Slide 18-

Li-Fraumeni p53 mutation Tumor suppressor gene 50% risk of cancer before 40yo 90% risk by 60yo Associated cancers Breast Sarcoma Brain Leukemia
Slide 19-

Li-Fraumeni Breast surveillance, prophylaxis as per BRCA Annual derm visit Annual whole body MRI Annual neuro exam Based on family’s history
Slide 20-

Recognition in the office *Family history – both form and verbal* Ages of onsets Multiple generations Polyps Pedigree Update family history annually Encourage them to ask
Slide 21-

Red Flags “EMR” Early Multiple Rare Early <50yo – breast, colon, endometrial Multiple 2 or more family members with breast, colon, ovarian, uterine, prostate, pancreatic, gastric Rare Ovarian, triple negative breast, 2 primary breast ca, male breast ca, CRC with abnormal MSI, sarcoma
Slide 22-

Now what? Refer for counseling and testing Trained medical professional Traditional genetic counselor
Slide 23-

Testing Pretest counseling Overview of sporadic, familial, hereditary . . . Risks of cancers in affected people Recommendations for carriers (and if negative) Possible test results (positive, negative, VUS) Test coverage Insurance implications (GINA) Family impact Emotional impact
Slide 24-

Testing Post test counseling Positive Negative VUS ***Specific plan, including responsible providers
Slide 25-

Testing logistics Buccal swab or blood sample Send to company Company checks insurance coverage, calls pt 3-4 week to result
Slide 26-

Hereditary Cancer Syndromes
Slide 27-

Single gene v. Multi-gene panels BREAST BRCA 1/2 STK11 PTEN CDN1 ATM PALB2 TP53 CHEK2 RAD51C BARDI
Slide 28-

Multi-gene panels Comprehensive panel Up to 32 genes Tumor tailored panel Breast, colorectal, ovarian , melanoma
Slide 29-

Multi-gene panel Pros Detect less common/less penetrant genes More efficient More cost-effective Cons Moderate risk genes without robust data to guide management Higher VUS rates
Slide 30-

Variants of uncertain significance Mutations with insufficient information to delineate risk Test affected family members Reclassification over time Counsel patients based on personal and family history
Slide 31-

Patient cases
Slide 32-

Stephanie L. 32 Breast - 30 Ovarian - 35 Breast - 45 Pancreatic - 55
Slide 33-

Stephanie L. 33 Breast - 30 Ovarian - 35 Breast - 45 Pancreatic - 55 BRCA 2 mutation
Slide 34-

Karen E. 34 Uterine - 56 Colon - 78 Breast - 66 Breast - 58 Kidney - 72
Slide 35-

Karen E. 35 Uterine - 56 Colon - 78 Breast - 66 Breast - 58 Kidney - 72 MSH2 del exons 1-6
Slide 36-

Karen E. 36 Uterine - 56 Colon - 78 Breast - 66 Breast - 58 Kidney - 72 MSH2 del exons 1-6 Breast - 59 Adrenal - 35
Slide 37-

Colorectal screening colonoscopy q1-2y starting 20-25yo annual colonoscopy starting 40yo Other cancers Annual mammogram and CBE q6m EGD q1-3 starting at 25yo UA (?cytology) annually Karen S. – recommendations 37
Slide 38-

Sandra M 38 Breast- 56 Colon - 78 Prostate - 66 Breast - 79 Breast - 45 BRCA2 of uncertain significance Management??
Slide 39-

Conclusions Imperative to take thorough FHx with annual updates Recognize patterns concerning for hereditary cancer syndromes Refer for genetic counseling +/- testing Ensure proper pre- and post-test counseling Well outlined management plan with specific providers identified