Ovarian or Endometrial Cancer? Consider Lynch Syndrome

Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. Discuss the relevance of Lynch syndrome in the management of women with personal or family history of ovarian syndrome
2. Recall which cancers may be associated with Lynch syndrome

Estimated time to complete activity: 0.25 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

Faculty: Susan J. Gross, MD, receives consulting fees from Genoox, Inc., and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from Dec 31 2017 through Dec 31 2019, participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.2 contact hours.

Read Disclaimer & Fine Print

CLINICAL ACTIONS:

Lynch syndrome, which has been previously referred to as hereditary non-polyposis colorectal cancer syndrome (HNPCC), increases gynecologic cancer risks namely endometrial, ovarian, and urothelial cancers in addition to colorectal and other associated cancers (gastric or small bowel cancers), glioblastoma, pancreatic or biliary tract cancer, and sebaceous adenocarcinoma.

Lynch syndrome should be considered in women with personal and/or family histories with features such as

Personal history of colorectal cancer
- < age 50 or
- ≥ age 50 with a 1st degree relative (parent, child or sibling) also having a diagnosis of colorectal cancer or endometrial cancer
Women with multiple colorectal cancers or colorectal cancer and endometrial cancer
- Level of suspicion should also be increased if other Lynch syndrome associated cancers are diagnosed in the patient and close relatives
Colorectal or endometrial cancer tumor profiles that demonstrate deficient mismatch repair, or microsatellite instability (MSI)
- Genes implicated in Lynch syndrome are known as mismatch repair (MMR) genes
Women who report a known gene mutation predisposing to cancer in the family
- Confirm the gene(s) tested and mutation(s) identified

NOTE: Because medical interventions can prevent severe morbidity and mortality, Lynch syndrome is on the ACMG list of ‘secondary’ findings. In summary, the ACMG document on reporting such findings makes the following recommendations

In the course of genetic testing for research or clinical care, the laboratory may identify variants in genes unrelated to the initial indication for testing, but nevertheless may have important health implications
Results of such ‘secondary findings’ should be communicated to the individuals who may benefit from this knowledge
An individual can ‘opt out’ of receiving ‘secondary findings’
ACMG secondary findings recommend reporting out known or expected pathogenic variants in the following MMR genes:
- MLH1, MSH2, MSH6, and PMS2

SYNOPSIS:

Lynch syndrome is inherited in an autosomal dominant fashion, however because of variable expressivity and reduced penetrance, the patient’s personal and family history must be carefully assessed. It is important to note earlier ages of onset and multiple cancers that may suggest Lynch syndrome or another hereditary cancer syndrome. It is critical that those at high risk be identified and referred for genetic counseling. Genetic counseling will allow for discussion of appropriate genetic testing, cancer screening and risk reduction options.

KEY POINTS:

When reviewing the family health history, remember that both the maternal and paternal family histories should both be carefully considered
Lynch syndrome greatly increases lifetime risk for:
- Ovarian cancer: 4-24%
  - Average lifetime risk in general population: 1.31%
- Endometrial cancer: 25-60%
  - Average lifetime risk in general population: 2.78%
- Colon cancer: 52–82%
  - Average lifetime risk in general population: 4.35% (females), 4.69% (males)
In the case of ovarian cancer, do not automatically assume BRCA1 or BRCA2 – consider Lynch syndrome and assess for additional clues such as other associated cancers
- ACOG does address multigene panels and finds that “Genetic testing may be performed using a panel of multiple genes through next-generation sequencing technology”
- Heritable cancer syndromes may overlap such that a strong family history for ovarian cancer may be the result of a pathogenic variant in BRCA1/2 or genes associated with Lynch Syndrome
The prospect of hereditary cancer risk can be anxiety provoking for the patient and family members, so it is important to reinforce the importance of information in allowing options for risk reduction and early cancer detection for those at highest risk