Lynch Syndrome Endometrial Cancer 2020 Estimated New Cases Early Detection Makes a Difference Endometrial Cancer Risk Factors Chronically increased estrogen levels Unopposed estrogen therapy Tamoxifen ID: 913390
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Slide1
Dario R. Roque, MD
Endometrial Cancer &
Lynch Syndrome
Slide2Endometrial Cancer 2020
Estimated New Cases
Slide3Early Detection Makes a Difference
Slide4Endometrial Cancer Risk Factors
Chronically increased estrogen levelsUnopposed estrogen therapy
Tamoxifen
Anovulation
Obesity
Estrogen secreting tumorsEarly onset menses or late menopauseHereditary FactorsLynch Syndrome
Slide5Lynch Syndrome (aka Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Inherited changes in genes that affect DNA mismatch repair (MMR) during DNA replication
Autosomal Dominant Inheritance
HAVING LYNCH SYNDROME DOES NOT MEAN YOU HAVE CANCER OR THAT YOU WILL DEFINITELY DEVELOP CANCER
Slide6Lynch Syndrome & Risk of Endometrial Cancer
Slide7Surveillance & Prevention StrategiesPrompt reporting and evaluation of any abnormal uterine bleeding
Consider screening with endometrial biopsy every 1-2 years starting at age 30-35Hysterectomy as risk reducing option if completed childbearing
Lynch Syndrome & Risk of Endometrial Cancer
Slide8What if I Already Have Endometrial Cancer?
Universal screening on all endometrial cancersAnalysis of tumor for presence of 4 genes that are known to malfunction/mutated in Lynch syndrome
MLH1, MSH2, MSH6, and PMS2
If all genes are expressed (normal)
Unlikely that a Lynch related pathogenic MMR deficiency is present
If one (or more) of the genes are not expressed Consider germline testingUnless defects in MLH1/PMS2
Hypermethylation
tumor testing
Microsatellite Instability (MSI)
Changes in DNA sequence between normal tissue and tumor tissue
Presence of MSI suggests malfunction in MMR genes
Majority of microsatellite unstable tumors
ARE NOT
due to Lynch Syndrome
Slide9Slide10Why Screening and Testing for Lynch Matters?
Slide11Slide12Emma Barber, MD, MS
Immunotherapy for Endometrial Cancer
Slide13Immune System and Cancer
Slide14Lynch Syndrome = Mismatch Repair Deficient
Slide15Mismatch Repair Deficient
Missing proteins that help the body repair DNACell accumulates many mistakesHigh mutation burdenMicrosatellite unstable
Hypermutator
phenotype
Immune system more likely to recognize things that are unlike it
Slide16Immune Check Point Inhibitors
CTLA-4
Ipilimumab
tremelimumab
PD-1
NivolumabPembrolizumab
PD-L1
Atezolizumab
Avelumab
Durvalumab
Slide17Clinical Trial Results
KEYNOTE-02824 women with PD1 positive recurrent endometrial cancer13% ORR
13% SD
KEYNOTE-158
49 women with MMR deficient endometrial cancer
ORR 57%Median PFS 25 months
Slide18Immunotherapy for non-biomarker selected endometrial cancer
Breakthrough FDA designation, now FDA approvedLenvatinib and
Pembrolizumab
54 patients
40% ORR
Slide19Ongoing Clinical Trials
NRG GY-018 – Chemotherapy and pembrolizumab for women with stage III/IV (measureable disease) or recurrent endometrial cancer
NRG GY-020
–
Pembrolizumab and radiation therapy for high intermediate risk endometrial cancerMolecular subtyping of endometrial cancer – does immunotherapy replace chemotherapy?
Slide20Thank you